NCT01124695
Version 128 to 129 · ECOG-ACRIN Cancer Research Group
Patch inspector
Manual review pending.
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Progression-free Survival by CYP2D6 Status in 2 Categories
/protocolSection/outcomesModule/primaryOutcomes/0/description primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority. Progression-free survival is defined as the time from registration to progression or death, whichever occurs first. Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression. Progression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame primary_outcome_any_change Any add/remove/replace under primary outcome measures is critical review priority. Assessed every 3 months for 2 years, then every 6 months up to 5 years
/protocolSection/designModule/designInfo/allocation design_info_change Design information changes can alter allocation, masking, model, or purpose and need review. NA
/protocolSection/designModule/designInfo/interventionModel design_info_change Design information changes can alter allocation, masking, model, or purpose and need review. SINGLE_GROUP
/protocolSection/designModule/enrollmentInfo/count enrollment_count_change Enrollment count changes can signal scope or feasibility shifts. 240
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/protocolSection/armsInterventionsModule/interventions/0/name arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. tamoxifen citrate
tamoxifen
/protocolSection/armsInterventionsModule/interventions/0/description arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. PO
/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. [ "Tamoxifen" ]
/protocolSection/armsInterventionsModule/interventions/0/otherNames arms_or_interventions_change Arms or interventions changes can alter treatment/comparator structure. [ "tamoxifen citrate", "Nolvadex", "NSC# 180973" ]
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{
"type": "EXPERIMENTAL",
"label": "Tamoxifen",
"description": "Patients receive oral tamoxifen citrate once daily on days 1-28.\nTreatment repeats every 28 days in the absence of disease progression or unacceptable toxicities.",
"interventionNames": [
"Drug: tamoxifen"
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] /protocolSection/eligibilityModule/eligibilityCriteria eligibility_criteria_change Eligibility criteria changes can alter the studied population. <p>DISEASE CHARACTERISTICS:</p><ul><li><p>Histologically confirmed adenocarcinoma of the breast</p><ul><li>Stage III (locally advanced), metastatic, or recurrent disease</li><li>Deemed not resectable</li></ul></li><li><p>Estrogen-receptor and/or progesterone-receptor positive disease</p><ul><li>Receptor status is based on most recent results</li><li>Receptor testing on metastatic disease is not required</li></ul></li><li>Measurable or non-measurable disease</li><li><p>History of CNS metastasis allowed provided it has been treated (surgery, radiotherapy, or radiosurgery) within the past 4 weeks and does not require medications to control symptoms</p><ul><li>No known leptomeningeal disease allowed</li></ul></li></ul><p>PATIENT CHARACTERISTICS:</p><ul><li>ECOG performance status 0-2</li><li>Menopausal status not specified</li><li>Total bilirubin ≤ 1.5 times upper limit of normal (ULN)</li><li>ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases present)</li><li>Not pregnant or nursing</li><li>Negative pregnancy test</li><li>Fertile patients must use effective nonhormonal contraception</li><li>No medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, assessment of response, or anticipated toxicities</li><li>More than 5 years since prior invasive malignancies except curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix</li></ul><p>PRIOR CONCURRENT THERAPY:</p><ul><li>See Disease Characteristics</li><li><p>No prior investigational agents in the metastatic setting</p><ul><li>Other prior investigational agents in any setting must have been completed at least 6 weeks prior to study registration and should be discussed with the study PI</li></ul></li><li><p>Prior tamoxifen as adjuvant treatment is allowed as long as the patient did not have disease relapse or progression while on adjuvant tamoxifen or within 4 weeks of last dose</p><ul><li>Prior tamoxifen for advanced disease is not allowed</li></ul></li><li><p>No prior chemotherapy or trastuzumab (Herceptin) for metastatic disease</p><ul><li>Prior chemotherapy, trastuzumab, or bevacizumab in the adjuvant setting allowed provided it has been completed ≥ 4 weeks before study therapy</li></ul></li><li><p>Patients must not have had more than 2 lines of non-hormonal treatment in the locally advanced or metastatic setting, including trastuzumab (Herceptin), bevacizumab, or other biologics</p><ul><li>Treatment in the advanced setting must have been completed at least 2 weeks prior to study initiation</li></ul></li><li>Prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane, aminoglutethamide) are allowed in the adjuvant or metastatic setting</li><li><p>At least 2 weeks since prior and no concurrent medications that are strong to moderate inhibitors of CYP2D6 and may alter tamoxifen citrate metabolism including, but not limited to, any of the following:</p><ul><li>Paroxetine (Paxil)</li><li>Fluoxetine (Prozac)</li><li>Bupropion (Wellbutrin)</li><li>Quinidine (Cardioquin)</li></ul></li><li><p>Patients may not initiate bisphosphonate therapy while receiving treatment on this study</p><ul><li>Patients who have begun receiving bisphosphonate therapy prior to registration may continue at the same intervals used prior to study registration</li></ul></li><li><p>Concurrent radiotherapy to painful sites of bone disease or areas of impending fractures allowed provided the following criteria are met:</p><ul><li>Radiotherapy was initiated before study entry</li><li>Sites of measurable or non-measurable disease are outside the radiotherapy port</li><li>Recovered from prior radiotherapy</li></ul></li><li>No other concurrent hormonal therapy</li><li>No concurrent chemotherapy</li></ul>
<p>Inclusion Criteria:</p><ul><li><p>Histologically confirmed adenocarcinoma of the breast</p><ul><li>Stage III (locally advanced), metastatic, or recurrent disease</li><li>Deemed not resectable</li></ul></li><li><p>Estrogen-receptor and/or progesterone-receptor positive disease</p><ul><li>Receptor status is based on most recent results</li></ul></li><li>Measurable or non-measurable disease</li><li>ECOG performance status 0-2</li><li>History of central nervous system (CNS) metastasis allowed provided it has been treated (surgery, radiotherapy, or radiosurgery) within the past 4 weeks and does not require medications to control symptoms</li><li>Total bilirubin ≤ 1.5 times upper limit of normal (ULN)</li><li>Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases present)</li><li>Negative pregnancy test</li><li>Fertile patients must use effective nonhormonal contraception</li><li>Disease-free of prior invasive malignancies for ≥ 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix</li><li>Prior chemotherapy, trastuzumab, or bevacizumab in the adjuvant setting allowed provided it has been completed ≥ 4 weeks before study therapy; other prior non-hormonal investigational agents in the adjuvant setting must have been completed at least 4 weeks prior to study registration and should be discussed with the study PI</li><li>Prior tamoxifen as adjuvant treatment is allowed as long as the patient did not have disease relapse or progression while on adjuvant tamoxifen or within 4 weeks of last dose</li><li>Treatment in the advanced setting must have been completed at least 2 weeks prior to study initiation</li><li>Prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane, aminoglutethamide) are allowed in the adjuvant or metastatic setting</li><li><p>At least 2 weeks since prior and no concurrent medications that are strong to moderate inhibitors of CYP2D6 and may alter tamoxifen citrate metabolism including, but not limited to, any of the following:</p><ul><li>Paroxetine (Paxil)</li><li>Fluoxetine (Prozac)</li><li>Bupropion (Wellbutrin)</li><li>Quinidine (Cardioquin)</li></ul></li><li><p>Concurrent radiotherapy to painful sites of bone disease or areas of impending fractures allowed provided the following criteria are met:</p><ul><li>Radiotherapy was initiated before study entry</li><li>Sites of measurable or non-measurable disease are outside the radiotherapy port</li><li>Recovered from prior radiotherapy</li></ul></li></ul><p>Exclusion Criteria:</p><ul><li>Pregnant or nursing</li><li>Concurrent chemotherapy</li><li>Leptomeningeal disease</li><li>Non-protocol concurrent hormonal therapy</li><li>Medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, assessment of response, or anticipated toxicities</li><li>Prior tamoxifen for advanced disease</li><li>More than 2 lines of non-hormonal treatment in the locally advanced or metastatic setting, including trastuzumab (Herceptin), bevacizumab, or other biologics</li><li><p>Starting bisphosphonate therapy while receiving treatment on this study</p><ul><li>Patients who have begun receiving bisphosphonate therapy prior to registration may continue at the same intervals used prior to study registration</li></ul></li></ul>
/protocolSection/eligibilityModule/maximumAge 120 Years
/protocolSection/outcomesModule/secondaryOutcomes/0/measure secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Correlation of CYP2D6 score (0 vs 1 vs 2) with PFS
Progression-free Survival by CYP2D6 Status in 3 Categories
/protocolSection/outcomesModule/secondaryOutcomes/0/description secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Progression-free survival is defined as the time from registration to progression or death, whichever occurs first. Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression. Progression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Assessed every 3 months for 2 years, then every 6 months up to 5 years
/protocolSection/outcomesModule/secondaryOutcomes/1/measure secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Correlation of CYP2D6 score (0 vs 1-2) with PFS at 6 months
Proportion of Patients Progression-free at 6 Months
/protocolSection/outcomesModule/secondaryOutcomes/1/description secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression. Progression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Assessed every 3 months for 6 months
/protocolSection/outcomesModule/secondaryOutcomes/2/measure secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Correlation of endoxifen concentration with response
Proportion of Patients With Response
/protocolSection/outcomesModule/secondaryOutcomes/2/description secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate response. Either complete response (CR) or partial response (PR) is considered as response. CR is defined as disappearance of all lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Assessed every 3 months for 2 years, then every 6 months up to 5 years
/protocolSection/outcomesModule/secondaryOutcomes/3/measure secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Correlation of CYP2D6 with response
Endoxifen Concentration by Response
/protocolSection/outcomesModule/secondaryOutcomes/3/description secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. <p>Endoxifen (ng/ml) was assessed at cycle 3.</p><p>Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate response. Either complete response (CR) or partial response (PR) is considered as response. CR is defined as disappearance of all lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</p>
/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. Endoxifen was assessed at cycle 3; response was assessed every 3 months for 2 years, then every 6 months up to 5 years
/protocolSection/outcomesModule/secondaryOutcomes/4 secondary_outcome_any_change Any add/remove/replace under secondary outcome measures is high review priority. {
"measure": "Progression-free Survival From 3 Months Post Registration",
"timeFrame": "Assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "<p>This is a landmark progression-free survival analysis at 3 months post registration.\nOnly patients who were progression-free and alive at 3 months were included.</p><p>Progression-free survival in this analysis is defined as the time from 3 months post registration to progression or death, whichever occurs first.\nResponse Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression.\nProgression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).\nIn addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</p>"
} /protocolSection/statusModule/statusVerifiedDate 2022-06
2023-02
/protocolSection/statusModule/lastUpdateSubmitDate 2022-06-08
2023-02-13
/protocolSection/statusModule/lastUpdatePostDateStruct/date 2022-06-10
2023-03-14
/protocolSection/statusModule/resultsFirstSubmitDate 2022-09-07
/protocolSection/statusModule/resultsFirstSubmitQcDate 2023-02-13
/protocolSection/statusModule/resultsFirstPostDateStruct {
"date": "2023-03-14",
"type": "ACTUAL"
} /protocolSection/descriptionModule/detailedDescription <p>OBJECTIVES:</p><p>Primary</p><ul><li>To correlate CYP2D6 score (0 vs 1-2) and progression-free survival (PFS) of patients with metastatic breast cancer treated with tamoxifen citrate.</li></ul><p>Secondary</p><ul><li>To correlate CYP2D6 score (0 vs 1 vs 2) and PFS of patients treated with this regimen.</li><li>To correlate CYP2D6 score (0 vs 1 + 2) and the proportion of these patients who are PFS at 6 months.</li><li>To correlate endoxifen concentration with response in patients treated with this regimen.</li><li>To correlate CYP2D6 with response in patients treated with this regimen.</li><li>To correlate the presence of candidate estrogen receptor (ESR) 1 and 2 variant alleles, UGT7, SULT1A1, and other candidate genes to PFS.</li></ul><p>OUTLINE: This is a multicenter study.</p><p>Patients receive oral tamoxifen citrate once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicities.</p><p>Blood, plasma, and tissue samples are collected periodically for laboratory studies.</p><p>After completion of study therapy, patients are followed up every 3-6 months for 5 years.</p>
<p>OBJECTIVES:</p><p>Primary</p><ul><li>To correlate CYP2D6 (Cytochrome P450 2D6) score (0 vs 1-2) and progression-free survival (PFS)</li></ul><p>Secondary</p><ul><li>To correlate CYP2D6 score (0 vs 1 vs 2) and PFS</li><li>To correlate CYP2D6 score (0 vs 1-2) and the proportion of these patients who are progression-free at 6 months.</li><li>To correlate endoxifen concentration with response</li><li>To correlate CYP2D6 with response</li><li>To correlate the presence of candidate estrogen receptor (ESR) 1 and 2 variant alleles, UDP-glucuronosyltransferases (UGT) 7, sulfotransferases (SULT) 1A1, other candidate genes and biomarkers to PFS and other tamoxifen related outcomes</li></ul><p>OUTLINE: This is a multicenter study.</p><p>Patients receive oral tamoxifen citrate once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicities.</p><p>Blood, plasma, and tissue samples are collected periodically for laboratory studies.</p><p>After completion of study therapy, patients are followed up every 3-6 months for 5 years.</p>
/protocolSection/conditionsModule/conditions/1 Stage IV Breast Cancer
/protocolSection/conditionsModule/keywords/1 male breast cancer
/protocolSection/ipdSharingStatementModule/ipdSharing UNDECIDED
YES
/protocolSection/ipdSharingStatementModule/description Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
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"date": "2022-09-07",
"type": "RELEASE"
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"date": "2022-10-04",
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"date": "2022-10-14",
"type": "RELEASE"
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/resultsSection {
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"pointOfContact": {
"email": "eatrials@jimmy.harvard.edu",
"phone": "617-632-3012",
"title": "Study Statistician",
"organization": "ECOG-ACRIN Statistical Office"
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"certainAgreement": {
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"timeFrame": "Assessed every 4 weeks while on treatment and for 30 days after the end of treatment up to 5 years",
"description": "<p>All patients enrolled are included in all-cause mortality analysis.\nPatients who received treatment with adverse event data available are included in AE analysis.</p><p>This is a single-arm study, so adverse events are reported for the Tamoxifen arm only, which is reported per arm.</p>",
"eventGroups": [
{
"id": "EG000",
"title": "Tamoxifen",
"description": "Patients receive oral tamoxifen citrate at 20 mg once daily on days 1-28.\nTreatment repeats every 28 days in the absence of disease progression or unacceptable toxicities.",
"otherNumAtRisk": 122,
"deathsNumAtRisk": 124,
"otherNumAffected": 18,
"seriousNumAtRisk": 122,
"deathsNumAffected": 69,
"seriousNumAffected": 30
}
],
"otherEvents": [
{
"term": "Fatigue",
"stats": [
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"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 18
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hot flashes",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 11
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Anemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 10
}
],
"organSystem": "Blood and lymphatic system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Edema limbs",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Constipation",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 9
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Nausea",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 14
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Vomiting",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 9
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Aspartate aminotransferase increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Anorexia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Arthralgia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 7
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Back pain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 17
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Bone pain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Anxiety",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 7
}
],
"organSystem": "Psychiatric disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Insomnia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 7
}
],
"organSystem": "Psychiatric disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Dyspnea",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "Respiratory, thoracic and mediastinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypertension",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 9
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
}
],
"seriousEvents": [
{
"term": "Anemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Blood and lymphatic system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Fatigue",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Aspartate aminotransferase increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Lymphocyte count decreased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 4
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Platelet count decreased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypercalcemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypertriglyceridemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 3
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Arthralgia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 3
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Back pain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 4
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Bone pain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 4
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Peripheral motor neuropathy",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Nervous system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Peripheral sensory neuropathy",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Nervous system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Thromboembolic event",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hearing impaired",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Ear and labyrinth disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Atrial fibrillation",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Cardiac disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Heart failure",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Cardiac disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Pericardial tamponade",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Cardiac disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Death NOS",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Edema limbs",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Skin ulceration",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Skin and subcutaneous tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Urticaria",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Skin and subcutaneous tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Constipation",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Diarrhea",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Obstruction gastric",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Pancreatitis",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Vomiting",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Cholecystitis",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Hepatobiliary disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Joint infection",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Infections and infestations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Sepsis",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Infections and infestations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Skin infection",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Infections and infestations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Alanine aminotransferase increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Alkaline phosphatase increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Creatinine increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Neutrophil count decreased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Weight gain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "White blood cell decreased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Acidosis",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Glucose intolerance",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hyperglycemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hyperkalemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypocalcemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypoglycemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Obesity",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Muscle weakness lower limb",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Pain in extremity",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Dizziness",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Nervous system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Headache",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Nervous system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Neoplasms - Other",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Neoplasms benign, malignant and unspecified (incl cysts and polyps)",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Confusion",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Psychiatric disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Dyspnea",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 3
}
],
"organSystem": "Respiratory, thoracic and mediastinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Respiratory failure",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Respiratory, thoracic and mediastinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Acute kidney injury",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Renal and urinary disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Chronic kidney disease",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Renal and urinary disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Surgical and medical procedures - Other",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Surgical and medical procedures",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypertension",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 3
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypotension",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
}
],
"frequencyThreshold": "5"
},
"outcomeMeasuresModule": {
"outcomeMeasures": [
{
"type": "PRIMARY",
"title": "Progression-free Survival by CYP2D6 Status in 2 Categories",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "2",
"groupId": "OG000"
},
{
"value": "83",
"groupId": "OG001"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "CYP2D6 - PM",
"description": "Patients with CYP2D6 score of 0 are considered as poor metabolizer (PM)."
},
{
"id": "OG001",
"title": "CYP2D6 - (IM+NM+UM)",
"description": "<p>Patients with CYP2D6 score >0 are included in the IM+NM+UM group.</p><p>Intermediate metabolizer (IM): CYP2D6 score >0 and <=1 Normal metabolizer (NM): CYP2D6 score >1 and <=2 Ultra-rapid metabolizer (UM): CYP2D6 score >2</p>"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "12.9",
"comment": "Only 2 patients were in this category.\nAmong these two, one was censored at baseline.\nAs only one patient contributed data, the 95% CI could not be calculated.",
"groupId": "OG000",
"lowerLimit": "NA",
"upperLimit": "NA"
},
{
"value": "6.9",
"groupId": "OG001",
"lowerLimit": "4.4",
"upperLimit": "8.5"
}
]
}
]
}
],
"paramType": "MEDIAN",
"timeFrame": "Assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "Progression-free survival is defined as the time from registration to progression or death, whichever occurs first.\nResponse Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression.\nProgression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).\nIn addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.",
"unitOfMeasure": "months",
"dispersionType": "95% Confidence Interval",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had a sample from baseline evaluable for CYP2D6 phenotype"
},
{
"type": "SECONDARY",
"title": "Progression-free Survival by CYP2D6 Status in 3 Categories",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "2",
"groupId": "OG000"
},
{
"value": "27",
"groupId": "OG001"
},
{
"value": "56",
"groupId": "OG002"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "CYP2D6 - PM",
"description": "Patients with CYP2D6 score of 0 are considered as poor metabolizer (PM)."
},
{
"id": "OG001",
"title": "CYP2D6 - IM",
"description": "Intermediate metabolizer (IM): CYP2D6 score >0 and <=1"
},
{
"id": "OG002",
"title": "CYP2D6 - NM+UM",
"description": "<p>Patients with CYP2D6 score >1 are included in the NM+UM group.</p><p>Normal metabolizer (NM): CYP2D6 score >1 and <=2 Ultra-rapid metabolizer (UM): CYP2D6 score >2</p>"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "12.9",
"comment": "Only 2 patients were in this category.\nAmong these two, one was censored at baseline.\nAs only one patient contributed data, the 95% CI could not be calculated.",
"groupId": "OG000",
"lowerLimit": "NA",
"upperLimit": "NA"
},
{
"value": "4.8",
"groupId": "OG001",
"lowerLimit": "2.7",
"upperLimit": "13.8"
},
{
"value": "7.4",
"groupId": "OG002",
"lowerLimit": "4.9",
"upperLimit": "10.3"
}
]
}
]
}
],
"paramType": "MEDIAN",
"timeFrame": "Assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "Progression-free survival is defined as the time from registration to progression or death, whichever occurs first.\nResponse Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression.\nProgression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).\nIn addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.",
"unitOfMeasure": "months",
"dispersionType": "95% Confidence Interval",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had a sample from baseline evaluable for CYP2D6 phenotype"
},
{
"type": "SECONDARY",
"title": "Proportion of Patients Progression-free at 6 Months",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "2",
"groupId": "OG000"
},
{
"value": "83",
"groupId": "OG001"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "CYP2D6 - PM",
"description": "Patients with CYP2D6 score of 0 are considered as poor metabolizer (PM)."
},
{
"id": "OG001",
"title": "CYP2D6 - (IM+NM+UM)",
"description": "<p>Patients with CYP2D6 score >0 are included in the IM+NM+UM group.</p><p>Intermediate metabolizer (IM): CYP2D6 score >0 and <=1 Normal metabolizer (NM): CYP2D6 score >1 and <=2 Ultra-rapid metabolizer (UM): CYP2D6 score >2</p>"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "1.0",
"groupId": "OG000",
"lowerLimit": "0.16",
"upperLimit": "1.00"
},
{
"value": "0.50",
"groupId": "OG001",
"lowerLimit": "0.39",
"upperLimit": "0.62"
}
]
}
]
}
],
"paramType": "NUMBER",
"timeFrame": "Assessed every 3 months for 6 months",
"description": "Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression.\nProgression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).\nIn addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.",
"unitOfMeasure": "proportion of participants",
"dispersionType": "95% Confidence Interval",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had a sample from baseline evaluable for CYP2D6 phenotype"
},
{
"type": "SECONDARY",
"title": "Proportion of Patients With Response",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "2",
"groupId": "OG000"
},
{
"value": "83",
"groupId": "OG001"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "CYP2D6 - PM",
"description": "Patients with CYP2D6 score of 0 are considered as poor metabolizer (PM)."
},
{
"id": "OG001",
"title": "CYP2D6 - (IM+NM+UM)",
"description": "<p>Patients with CYP2D6 score >0 are included in the IM+NM+UM group.</p><p>Intermediate metabolizer (IM): CYP2D6 score >0 and <=1 Normal metabolizer (NM): CYP2D6 score >1 and <=2 Ultra-rapid metabolizer (UM): CYP2D6 score >2</p>"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "0",
"groupId": "OG000",
"lowerLimit": "0.0",
"upperLimit": "0.84"
},
{
"value": "0.13",
"groupId": "OG001",
"lowerLimit": "0.07",
"upperLimit": "0.22"
}
]
}
]
}
],
"paramType": "NUMBER",
"timeFrame": "Assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate response.\nEither complete response (CR) or partial response (PR) is considered as response.\nCR is defined as disappearance of all lesions.\nPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.",
"unitOfMeasure": "proportion of participants",
"dispersionType": "95% Confidence Interval",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had a sample from baseline evaluable for CYP2D6 phenotype"
},
{
"type": "SECONDARY",
"title": "Endoxifen Concentration by Response",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "6",
"groupId": "OG000"
},
{
"value": "57",
"groupId": "OG001"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "Responders",
"description": "Patients with CR or PR per RECIST 1.1"
},
{
"id": "OG001",
"title": "Non-responders",
"description": "Patients without CR or PR per RECIST 1.1"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "17.5",
"groupId": "OG000",
"lowerLimit": "7.5",
"upperLimit": "45.2"
},
{
"value": "17.2",
"groupId": "OG001",
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"upperLimit": "67.9"
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]
}
]
}
],
"paramType": "MEDIAN",
"timeFrame": "Endoxifen was assessed at cycle 3; response was assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "<p>Endoxifen (ng/ml) was assessed at cycle 3.</p><p>Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate response.\nEither complete response (CR) or partial response (PR) is considered as response.\nCR is defined as disappearance of all lesions.\nPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</p>",
"unitOfMeasure": "ng/ml",
"dispersionType": "Full Range",
"reportingStatus": "POSTED",
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},
{
"type": "SECONDARY",
"title": "Progression-free Survival From 3 Months Post Registration",
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{
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"paramType": "MEDIAN",
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"description": "<p>This is a landmark progression-free survival analysis at 3 months post registration.\nOnly patients who were progression-free and alive at 3 months were included.</p><p>Progression-free survival in this analysis is defined as the time from 3 months post registration to progression or death, whichever occurs first.\nResponse Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression.\nProgression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).\nIn addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</p>",
"unitOfMeasure": "months",
"dispersionType": "95% Confidence Interval",
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"periods": [
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"value": "<p>Inclusion Criteria:</p><ul><li><p>Histologically confirmed adenocarcinoma of the breast</p><ul><li>Stage III (locally advanced), metastatic, or recurrent disease</li><li>Deemed not resectable</li></ul></li><li><p>Estrogen-receptor and/or progesterone-receptor positive disease</p><ul><li>Receptor status is based on most recent results</li></ul></li><li>Measurable or non-measurable disease</li><li>ECOG performance status 0-2</li><li>History of central nervous system (CNS) metastasis allowed provided it has been treated (surgery, radiotherapy, or radiosurgery) within the past 4 weeks and does not require medications to control symptoms</li><li>Total bilirubin ≤ 1.5 times upper limit of normal (ULN)</li><li>Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 times ULN (≤ 5 times ULN if liver metastases present)</li><li>Negative pregnancy test</li><li>Fertile patients must use effective nonhormonal contraception</li><li>Disease-free of prior invasive malignancies for ≥ 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix</li><li>Prior chemotherapy, trastuzumab, or bevacizumab in the adjuvant setting allowed provided it has been completed ≥ 4 weeks before study therapy; other prior non-hormonal investigational agents in the adjuvant setting must have been completed at least 4 weeks prior to study registration and should be discussed with the study PI</li><li>Prior tamoxifen as adjuvant treatment is allowed as long as the patient did not have disease relapse or progression while on adjuvant tamoxifen or within 4 weeks of last dose</li><li>Treatment in the advanced setting must have been completed at least 2 weeks prior to study initiation</li><li>Prior aromatase inhibitors (e.g., anastrozole, letrozole, exemestane, aminoglutethamide) are allowed in the adjuvant or metastatic setting</li><li><p>At least 2 weeks since prior and no concurrent medications that are strong to moderate inhibitors of CYP2D6 and may alter tamoxifen citrate metabolism including, but not limited to, any of the following:</p><ul><li>Paroxetine (Paxil)</li><li>Fluoxetine (Prozac)</li><li>Bupropion (Wellbutrin)</li><li>Quinidine (Cardioquin)</li></ul></li><li><p>Concurrent radiotherapy to painful sites of bone disease or areas of impending fractures allowed provided the following criteria are met:</p><ul><li>Radiotherapy was initiated before study entry</li><li>Sites of measurable or non-measurable disease are outside the radiotherapy port</li><li>Recovered from prior radiotherapy</li></ul></li></ul><p>Exclusion Criteria:</p><ul><li>Pregnant or nursing</li><li>Concurrent chemotherapy</li><li>Leptomeningeal disease</li><li>Non-protocol concurrent hormonal therapy</li><li>Medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, assessment of response, or anticipated toxicities</li><li>Prior tamoxifen for advanced disease</li><li>More than 2 lines of non-hormonal treatment in the locally advanced or metastatic setting, including trastuzumab (Herceptin), bevacizumab, or other biologics</li><li><p>Starting bisphosphonate therapy while receiving treatment on this study</p><ul><li>Patients who have begun receiving bisphosphonate therapy prior to registration may continue at the same intervals used prior to study registration</li></ul></li></ul>"
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"adverseEventsModule": {
"timeFrame": "Assessed every 4 weeks while on treatment and for 30 days after the end of treatment up to 5 years",
"description": "<p>All patients enrolled are included in all-cause mortality analysis.\nPatients who received treatment with adverse event data available are included in AE analysis.</p><p>This is a single-arm study, so adverse events are reported for the Tamoxifen arm only, which is reported per arm.</p>",
"eventGroups": [
{
"id": "EG000",
"title": "Tamoxifen",
"description": "Patients receive oral tamoxifen citrate at 20 mg once daily on days 1-28.\nTreatment repeats every 28 days in the absence of disease progression or unacceptable toxicities.",
"otherNumAtRisk": 122,
"deathsNumAtRisk": 124,
"otherNumAffected": 18,
"seriousNumAtRisk": 122,
"deathsNumAffected": 69,
"seriousNumAffected": 30
}
],
"otherEvents": [
{
"term": "Fatigue",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 18
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hot flashes",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 11
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Anemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 10
}
],
"organSystem": "Blood and lymphatic system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Edema limbs",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Constipation",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 9
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Nausea",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 14
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Vomiting",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 9
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Aspartate aminotransferase increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Anorexia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Arthralgia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 7
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Back pain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 17
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Bone pain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Anxiety",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 7
}
],
"organSystem": "Psychiatric disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Insomnia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 7
}
],
"organSystem": "Psychiatric disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Dyspnea",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 8
}
],
"organSystem": "Respiratory, thoracic and mediastinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypertension",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 9
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
}
],
"seriousEvents": [
{
"term": "Anemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Blood and lymphatic system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Fatigue",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Aspartate aminotransferase increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Lymphocyte count decreased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 4
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Platelet count decreased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypercalcemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypertriglyceridemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 3
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Arthralgia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 3
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Back pain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 4
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Bone pain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 4
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Peripheral motor neuropathy",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Nervous system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Peripheral sensory neuropathy",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Nervous system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Thromboembolic event",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hearing impaired",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Ear and labyrinth disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Atrial fibrillation",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Cardiac disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Heart failure",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Cardiac disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Pericardial tamponade",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Cardiac disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Death NOS",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Edema limbs",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "General disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Skin ulceration",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Skin and subcutaneous tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Urticaria",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Skin and subcutaneous tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Constipation",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Diarrhea",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Obstruction gastric",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Pancreatitis",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Vomiting",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Gastrointestinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Cholecystitis",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Hepatobiliary disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Joint infection",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Infections and infestations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Sepsis",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Infections and infestations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Skin infection",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Infections and infestations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Alanine aminotransferase increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Alkaline phosphatase increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Creatinine increased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Neutrophil count decreased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Weight gain",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "White blood cell decreased",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Investigations",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Acidosis",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Glucose intolerance",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hyperglycemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hyperkalemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypocalcemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypoglycemia",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Obesity",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Metabolism and nutrition disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Muscle weakness lower limb",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Pain in extremity",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Musculoskeletal and connective tissue disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Dizziness",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Nervous system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Headache",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Nervous system disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Neoplasms - Other",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Neoplasms benign, malignant and unspecified (incl cysts and polyps)",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Confusion",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Psychiatric disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Dyspnea",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 3
}
],
"organSystem": "Respiratory, thoracic and mediastinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Respiratory failure",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Respiratory, thoracic and mediastinal disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Acute kidney injury",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 2
}
],
"organSystem": "Renal and urinary disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Chronic kidney disease",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Renal and urinary disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Surgical and medical procedures - Other",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Surgical and medical procedures",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypertension",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 3
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
},
{
"term": "Hypotension",
"stats": [
{
"groupId": "EG000",
"numAtRisk": 122,
"numAffected": 1
}
],
"organSystem": "Vascular disorders",
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"sourceVocabulary": "CTCAE 4.0"
}
],
"frequencyThreshold": "5"
},
"outcomeMeasuresModule": {
"outcomeMeasures": [
{
"type": "PRIMARY",
"title": "Progression-free Survival by CYP2D6 Status in 2 Categories",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "2",
"groupId": "OG000"
},
{
"value": "83",
"groupId": "OG001"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "CYP2D6 - PM",
"description": "Patients with CYP2D6 score of 0 are considered as poor metabolizer (PM)."
},
{
"id": "OG001",
"title": "CYP2D6 - (IM+NM+UM)",
"description": "<p>Patients with CYP2D6 score >0 are included in the IM+NM+UM group.</p><p>Intermediate metabolizer (IM): CYP2D6 score >0 and <=1 Normal metabolizer (NM): CYP2D6 score >1 and <=2 Ultra-rapid metabolizer (UM): CYP2D6 score >2</p>"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "12.9",
"comment": "Only 2 patients were in this category.\nAmong these two, one was censored at baseline.\nAs only one patient contributed data, the 95% CI could not be calculated.",
"groupId": "OG000",
"lowerLimit": "NA",
"upperLimit": "NA"
},
{
"value": "6.9",
"groupId": "OG001",
"lowerLimit": "4.4",
"upperLimit": "8.5"
}
]
}
]
}
],
"paramType": "MEDIAN",
"timeFrame": "Assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "Progression-free survival is defined as the time from registration to progression or death, whichever occurs first.\nResponse Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression.\nProgression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).\nIn addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.",
"unitOfMeasure": "months",
"dispersionType": "95% Confidence Interval",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had a sample from baseline evaluable for CYP2D6 phenotype"
},
{
"type": "SECONDARY",
"title": "Progression-free Survival by CYP2D6 Status in 3 Categories",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "2",
"groupId": "OG000"
},
{
"value": "27",
"groupId": "OG001"
},
{
"value": "56",
"groupId": "OG002"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "CYP2D6 - PM",
"description": "Patients with CYP2D6 score of 0 are considered as poor metabolizer (PM)."
},
{
"id": "OG001",
"title": "CYP2D6 - IM",
"description": "Intermediate metabolizer (IM): CYP2D6 score >0 and <=1"
},
{
"id": "OG002",
"title": "CYP2D6 - NM+UM",
"description": "<p>Patients with CYP2D6 score >1 are included in the NM+UM group.</p><p>Normal metabolizer (NM): CYP2D6 score >1 and <=2 Ultra-rapid metabolizer (UM): CYP2D6 score >2</p>"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "12.9",
"comment": "Only 2 patients were in this category.\nAmong these two, one was censored at baseline.\nAs only one patient contributed data, the 95% CI could not be calculated.",
"groupId": "OG000",
"lowerLimit": "NA",
"upperLimit": "NA"
},
{
"value": "4.8",
"groupId": "OG001",
"lowerLimit": "2.7",
"upperLimit": "13.8"
},
{
"value": "7.4",
"groupId": "OG002",
"lowerLimit": "4.9",
"upperLimit": "10.3"
}
]
}
]
}
],
"paramType": "MEDIAN",
"timeFrame": "Assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "Progression-free survival is defined as the time from registration to progression or death, whichever occurs first.\nResponse Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression.\nProgression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).\nIn addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.",
"unitOfMeasure": "months",
"dispersionType": "95% Confidence Interval",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had a sample from baseline evaluable for CYP2D6 phenotype"
},
{
"type": "SECONDARY",
"title": "Proportion of Patients Progression-free at 6 Months",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "2",
"groupId": "OG000"
},
{
"value": "83",
"groupId": "OG001"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "CYP2D6 - PM",
"description": "Patients with CYP2D6 score of 0 are considered as poor metabolizer (PM)."
},
{
"id": "OG001",
"title": "CYP2D6 - (IM+NM+UM)",
"description": "<p>Patients with CYP2D6 score >0 are included in the IM+NM+UM group.</p><p>Intermediate metabolizer (IM): CYP2D6 score >0 and <=1 Normal metabolizer (NM): CYP2D6 score >1 and <=2 Ultra-rapid metabolizer (UM): CYP2D6 score >2</p>"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "1.0",
"groupId": "OG000",
"lowerLimit": "0.16",
"upperLimit": "1.00"
},
{
"value": "0.50",
"groupId": "OG001",
"lowerLimit": "0.39",
"upperLimit": "0.62"
}
]
}
]
}
],
"paramType": "NUMBER",
"timeFrame": "Assessed every 3 months for 6 months",
"description": "Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression.\nProgression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).\nIn addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.",
"unitOfMeasure": "proportion of participants",
"dispersionType": "95% Confidence Interval",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had a sample from baseline evaluable for CYP2D6 phenotype"
},
{
"type": "SECONDARY",
"title": "Proportion of Patients With Response",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "2",
"groupId": "OG000"
},
{
"value": "83",
"groupId": "OG001"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "CYP2D6 - PM",
"description": "Patients with CYP2D6 score of 0 are considered as poor metabolizer (PM)."
},
{
"id": "OG001",
"title": "CYP2D6 - (IM+NM+UM)",
"description": "<p>Patients with CYP2D6 score >0 are included in the IM+NM+UM group.</p><p>Intermediate metabolizer (IM): CYP2D6 score >0 and <=1 Normal metabolizer (NM): CYP2D6 score >1 and <=2 Ultra-rapid metabolizer (UM): CYP2D6 score >2</p>"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "0",
"groupId": "OG000",
"lowerLimit": "0.0",
"upperLimit": "0.84"
},
{
"value": "0.13",
"groupId": "OG001",
"lowerLimit": "0.07",
"upperLimit": "0.22"
}
]
}
]
}
],
"paramType": "NUMBER",
"timeFrame": "Assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate response.\nEither complete response (CR) or partial response (PR) is considered as response.\nCR is defined as disappearance of all lesions.\nPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.",
"unitOfMeasure": "proportion of participants",
"dispersionType": "95% Confidence Interval",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had a sample from baseline evaluable for CYP2D6 phenotype"
},
{
"type": "SECONDARY",
"title": "Endoxifen Concentration by Response",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "6",
"groupId": "OG000"
},
{
"value": "57",
"groupId": "OG001"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "Responders",
"description": "Patients with CR or PR per RECIST 1.1"
},
{
"id": "OG001",
"title": "Non-responders",
"description": "Patients without CR or PR per RECIST 1.1"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "17.5",
"groupId": "OG000",
"lowerLimit": "7.5",
"upperLimit": "45.2"
},
{
"value": "17.2",
"groupId": "OG001",
"lowerLimit": "2.0",
"upperLimit": "67.9"
}
]
}
]
}
],
"paramType": "MEDIAN",
"timeFrame": "Endoxifen was assessed at cycle 3; response was assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "<p>Endoxifen (ng/ml) was assessed at cycle 3.</p><p>Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate response.\nEither complete response (CR) or partial response (PR) is considered as response.\nCR is defined as disappearance of all lesions.\nPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</p>",
"unitOfMeasure": "ng/ml",
"dispersionType": "Full Range",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had a sample at cycle 3 for endoxifen concentration evaluation"
},
{
"type": "SECONDARY",
"title": "Progression-free Survival From 3 Months Post Registration",
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "21",
"groupId": "OG000"
},
{
"value": "22",
"groupId": "OG001"
}
]
}
],
"groups": [
{
"id": "OG000",
"title": "Endoxifen High",
"description": "Patients with endoxifen at 3 months higher than median (15.5 ng/ml)"
},
{
"id": "OG001",
"title": "Endoxifen Low",
"description": "Patients with endoxifen at 3 months lower than or equal to median (15.5 ng/ml)"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "13.8",
"groupId": "OG000",
"lowerLimit": "6.5",
"upperLimit": "16.6"
},
{
"value": "11.1",
"groupId": "OG001",
"lowerLimit": "5.3",
"upperLimit": "19.3"
}
]
}
]
}
],
"paramType": "MEDIAN",
"timeFrame": "Assessed every 3 months for 2 years, then every 6 months up to 5 years",
"description": "<p>This is a landmark progression-free survival analysis at 3 months post registration.\nOnly patients who were progression-free and alive at 3 months were included.</p><p>Progression-free survival in this analysis is defined as the time from 3 months post registration to progression or death, whichever occurs first.\nResponse Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to evaluate progression.\nProgression is defined as appearance of one or more new lesions or unequivocal progression of existing non-target lesions or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).\nIn addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</p>",
"unitOfMeasure": "months",
"dispersionType": "95% Confidence Interval",
"reportingStatus": "POSTED",
"populationDescription": "Eligible and treated patients who had endoxifen level assessed at 3 months and were progression-free and alive at 3 months from registration"
}
]
},
"participantFlowModule": {
"groups": [
{
"id": "FG000",
"title": "Tamoxifen",
"description": "Patients receive oral tamoxifen citrate at 20 mg once daily on days 1-28.\nTreatment repeats every 28 days in the absence of disease progression or unacceptable toxicities."
}
],
"periods": [
{
"title": "Overall Study",
"milestones": [
{
"type": "STARTED",
"achievements": [
{
"groupId": "FG000",
"numSubjects": "124"
}
]
},
{
"type": "Treated",
"achievements": [
{
"groupId": "FG000",
"numSubjects": "122"
}
]
},
{
"type": "Eligible and Treated",
"achievements": [
{
"groupId": "FG000",
"numSubjects": "113"
}
]
},
{
"type": "Eligible and Treated and Had CYP2D6 Score",
"achievements": [
{
"groupId": "FG000",
"numSubjects": "85"
}
]
},
{
"type": "Eligible and Treated and Had Cycle 3 Edoxifen Evaluation",
"achievements": [
{
"groupId": "FG000",
"numSubjects": "63"
}
]
},
{
"type": "Eligible and Treated Patients With 3-month Endoxifen and Were Progression-free and Alive at 3 Months",
"achievements": [
{
"groupId": "FG000",
"numSubjects": "43"
}
]
},
{
"type": "COMPLETED",
"achievements": [
{
"groupId": "FG000",
"numSubjects": "1"
}
]
},
{
"type": "NOT COMPLETED",
"achievements": [
{
"groupId": "FG000",
"numSubjects": "123"
}
]
}
],
"dropWithdraws": [
{
"type": "Disease progression",
"reasons": [
{
"groupId": "FG000",
"numSubjects": "77"
}
]
},
{
"type": "Adverse Event",
"reasons": [
{
"groupId": "FG000",
"numSubjects": "11"
}
]
},
{
"type": "Death",
"reasons": [
{
"groupId": "FG000",
"numSubjects": "1"
}
]
},
{
"type": "Withdrawal by Subject",
"reasons": [
{
"groupId": "FG000",
"numSubjects": "7"
}
]
},
{
"type": "Physician Decision",
"reasons": [
{
"groupId": "FG000",
"numSubjects": "3"
}
]
},
{
"type": "Alternative therapy",
"reasons": [
{
"groupId": "FG000",
"numSubjects": "9"
}
]
},
{
"type": "No documentation that patient went off treatment",
"reasons": [
{
"groupId": "FG000",
"numSubjects": "4"
}
]
},
{
"type": "Ineligible",
"reasons": [
{
"groupId": "FG000",
"numSubjects": "9"
}
]
},
{
"type": "Ineligible and never start treatment",
"reasons": [
{
"groupId": "FG000",
"numSubjects": "2"
}
]
}
]
}
],
"recruitmentDetails": "The study was activated on September 21, 2010 and closed on October 22, 2015 for a total of 124 patients enrolled."
},
"baselineCharacteristicsModule": {
"denoms": [
{
"units": "Participants",
"counts": [
{
"value": "113",
"groupId": "BG000"
}
]
}
],
"groups": [
{
"id": "BG000",
"title": "Tamoxifen",
"description": "Patients receive oral tamoxifen citrate at 20 mg once daily on days 1-28.\nTreatment repeats every 28 days in the absence of disease progression or unacceptable toxicities."
}
],
"measures": [
{
"title": "Age, Continuous",
"classes": [
{
"categories": [
{
"measurements": [
{
"value": "62",
"groupId": "BG000",
"lowerLimit": "36",
"upperLimit": "94"
}
]
}
]
}
],
"paramType": "MEDIAN",
"unitOfMeasure": "years",
"dispersionType": "FULL_RANGE"
},
{
"title": "Sex: Female, Male",
"classes": [
{
"categories": [
{
"title": "Female",
"measurements": [
{
"value": "111",
"groupId": "BG000"
}
]
},
{
"title": "Male",
"measurements": [
{
"value": "2",
"groupId": "BG000"
}
]
}
]
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"unitOfMeasure": "Participants"
},
{
"title": "Ethnicity (NIH/OMB)",
"classes": [
{
"categories": [
{
"title": "Hispanic or Latino",
"measurements": [
{
"value": "33",
"groupId": "BG000"
}
]
},
{
"title": "Not Hispanic or Latino",
"measurements": [
{
"value": "77",
"groupId": "BG000"
}
]
},
{
"title": "Unknown or Not Reported",
"measurements": [
{
"value": "3",
"groupId": "BG000"
}
]
}
]
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"unitOfMeasure": "Participants"
},
{
"title": "Race (NIH/OMB)",
"classes": [
{
"categories": [
{
"title": "American Indian or Alaska Native",
"measurements": [
{
"value": "0",
"groupId": "BG000"
}
]
},
{
"title": "Asian",
"measurements": [
{
"value": "7",
"groupId": "BG000"
}
]
},
{
"title": "Native Hawaiian or Other Pacific Islander",
"measurements": [
{
"value": "0",
"groupId": "BG000"
}
]
},
{
"title": "Black or African American",
"measurements": [
{
"value": "6",
"groupId": "BG000"
}
]
},
{
"title": "White",
"measurements": [
{
"value": "97",
"groupId": "BG000"
}
]
},
{
"title": "More than one race",
"measurements": [
{
"value": "0",
"groupId": "BG000"
}
]
},
{
"title": "Unknown or Not Reported",
"measurements": [
{
"value": "3",
"groupId": "BG000"
}
]
}
]
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"unitOfMeasure": "Participants"
},
{
"title": "CYP2D6 phenotype",
"classes": [
{
"categories": [
{
"title": "Poor metabolizer",
"measurements": [
{
"value": "2",
"groupId": "BG000"
}
]
},
{
"title": "Intermediate metabolizer",
"measurements": [
{
"value": "27",
"groupId": "BG000"
}
]
},
{
"title": "Normal metabolizer",
"measurements": [
{
"value": "50",
"groupId": "BG000"
}
]
},
{
"title": "Ultra-rapid metabolizer",
"measurements": [
{
"value": "6",
"groupId": "BG000"
}
]
},
{
"title": "Missing",
"measurements": [
{
"value": "28",
"groupId": "BG000"
}
]
}
]
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"unitOfMeasure": "Participants"
}
],
"populationDescription": "Eligible and treated patients are included in this analysis.\nThis is the primary analysis population."
}
}
},
{
"op": "add",
"path": "/documentSection",
"value": {
"largeDocumentModule": {
"largeDocs": [
{
"date": "2014-05-01",
"size": 608025,
"label": "Study Protocol and Statistical Analysis Plan",
"hasIcf": false,
"hasSap": true,
"filename": "Prot_SAP_000.pdf",
"typeAbbrev": "Prot_SAP",
"uploadDate": "2022-08-25T16:19",
"hasProtocol": true
}
]
}
}
}
]