Raw JSON Patch
[
{
"op": "replace",
"path": "/protocolSection/statusModule/statusVerifiedDate",
"value": "2018-08"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/primaryCompletionDateStruct/date",
"value": "2019-12"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdateSubmitDate",
"value": "2018-08-31"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
"value": "2018-09-05"
},
{
"op": "add",
"path": "/protocolSection/sponsorCollaboratorsModule/collaborators",
"value": [
{
"name": "Bayer",
"class": "INDUSTRY"
}
]
},
{
"op": "replace",
"path": "/protocolSection/descriptionModule/detailedDescription",
"value": "<p>This is a Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3.\nPatients with NTRK1, NTRK2 or NTRK3 fusion-positive cancers will be identified through molecular assay.</p><p>Larotrectinib (LOXO-101) will be administered orally at 100mg twice daily (BID), with each cycle consisting of 28 days of dosing administered on a continuous basis.</p><p>The study will analyze 9 cohorts of patients with tumors bearing NTRK fusions, including non small cell lung cancer, thyroid cancer, sarcoma, colorectal cancer, salivary gland cancer, biliary cancer and primary CNS tumor, as well as a cohort that will enroll patients not included in the histologies listed above.\nCohort 9 will include patients who meet criteria for Cohorts 1 to 8, but with documented NTRK fusion from a laboratory where CLIA or equivalent certification cannot be confirmed by the Sponsor at the time of consent.</p>"
},
{
"op": "replace",
"path": "/protocolSection/designModule/enrollmentInfo/count",
"value": 176
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/0/description",
"value": "Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/0",
"value": "Drug: Larotrectinib LOXO-101"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/1/description",
"value": "Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/1/interventionNames/0",
"value": "Drug: Larotrectinib LOXO-101"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/2/description",
"value": "Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/2/interventionNames/0",
"value": "Drug: Larotrectinib LOXO-101"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/3/description",
"value": "Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/3/interventionNames/0",
"value": "Drug: Larotrectinib LOXO-101"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/4/description",
"value": "Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/4/interventionNames/0",
"value": "Drug: Larotrectinib LOXO-101"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/5/description",
"value": "Adult Solid Tumors Measurable Disease by RECIST 1.1 Oral larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/5/interventionNames/0",
"value": "Drug: Larotrectinib LOXO-101"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/6/description",
"value": "Brain Tumor Measurable by RANO Oral larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/6/interventionNames/0",
"value": "Drug: Larotrectinib LOXO-101"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/7/description",
"value": "Tumor Histology not in Cohorts 1-7 Evaluable but not Measurable Disease Oral larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/7/interventionNames/0",
"value": "Drug: Larotrectinib LOXO-101"
},
{
"op": "add",
"path": "/protocolSection/armsInterventionsModule/armGroups/8",
"value": {
"type": "OTHER",
"label": "Eligible for cohorts 1-8 but lab certification not confirmed",
"description": "Subjects eligible for Cohorts 1-8, but lab CLIA- or equivalent certification cannot be confirmed at time of Subjects eligible for Cohorts 1-8, but lab CLIA- or equivalent certification cannot be confirmed at time of consent Oral larotrectinib (LOXO-101)",
"interventionNames": [
"Drug: Larotrectinib LOXO-101"
]
}
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/interventions/0/name",
"value": "Larotrectinib LOXO-101"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/interventions/0/description",
"value": "Oral capsule of larotrectinib (LOXO-101) - 100mg BID"
},
{
"op": "add",
"path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/3",
"value": "Eligible for cohorts 1-8 but lab certification not confirmed"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
"value": "Overall Response Rate as determined by an independent radiology review committee and measured by the proportion of subjects with best overall confirmed response of complete response (CR) or partial response (PR) by RECISTv1.1 or RANO criteria"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
"value": "Overall Response Rate of confirmed CR or PR as determined by the treating investigator Overall Response Rate based on the treating Investigator's response assessment using RECISTv1.1 or RANO criteria, as appropriate to tumor type."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
"value": "To estimate the proportion of subjects that has any tumor regression as a best response."
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/description"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
"value": "Duration of Progression Free Survival following initiation of larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/description",
"value": "Number of months from initiation of larotrectinib (LOXO-101) to the earlier of disease progression or death due to any cause."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
"value": "Up to 30 months"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
"value": "Duration of overall survival (OS) following initiation of larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/description",
"value": "Number of months from the initiation of larotrectinib (LOXO-101) to the date of death due to any cause."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
"value": "Through study completion up to 42 months"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/6/measure",
"value": "To assess the safety profile and tolerability of larotrectinib (LOXO-101)."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
"value": "Through study completion up to 42 months"
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/6/description",
"value": "Incidence, duration, and severity of adverse events"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/7/measure",
"value": "Comparison of Progression Free Survival following initiation of larotrectinib (LOXO-101) to that following the line of therapy immediately preceding larotrectinib (LOXO-101) in each subject who has received prior therapy."
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/7/description",
"value": "Number of months from initiation of larotrectinib (LOXO-101) to the earlier of disease progression or death due to any cause"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/8/measure",
"value": "Evaluate the clinical benefit rate (CBR) based on the proportion of subjects with best overall response of CR, PR, or stable disease lasting 16 or more weeks following initiation of larotrectinib (LOXO-101)"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/9/measure",
"value": ""Evaluate the concordance of prior molecular profiling that detected an NTRK fusion within the subject's tumor with the diagnostic test being evaluated by the Sponsor""
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/10"
},
{
"op": "replace",
"path": "/protocolSection/eligibilityModule/eligibilityCriteria",
"value": "<p>Key Inclusion Criteria:</p><ol><li>Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories.\nSubjects who have NTRK gene fusion identified in a lab where certification of the lab cannot be confirmed by the Sponsor at the time of consent may enroll to Cohort 9.</li><li>Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy.</li><li><p>Adequate organ function as defined by the following criteria:</p><ul><li>Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) < 2.5 upper limit of normal (ULN), or AST and ALT < 5 ULN if liver function abnormalities are due to underlying malignancy.</li><li>Total bilirubin < 2.5 x ULN, except in the setting of biliary obstruction.\nSubjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible</li><li>Serum creatinine < 2.0 x ULN OR an estimated glomerular filtration rate ≥ 30 mL/minute using the Cockcroft-Gault formula</li><li>ECOG score < 3 (age >16 years) or Lansky Performance Score (LPS) >40% (age <16 years).\nIf enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) (age >16 years) or LPS (age <16 years) >50%</li><li>Archived tumor tissue.\nIf archival tissue is known to not be available, then an on-study tumor biopsy should be attempted if it can be safely performed.</li></ul></li></ol><p>Key Exclusion Criteria:</p><ol><li>Symptomatic or unstable brain metastases.\n(Note: Subjects with asymptomatic brain metastases are eligible to participate in the study).\nSubjects with primary CNS tumors are eligible.</li><li>Investigational agent or anticancer therapy within 2 weeks prior to the planned start of larotrectinib (LOXO-101) or 5 half-lives, whichever is shorter, and without recovery of clinically significant toxicities from that therapy.</li><li>Pregnancy or lactation.</li></ol>"
},
{
"op": "remove",
"path": "/protocolSection/contactsLocationsModule/locations/7"
},
{
"op": "remove",
"path": "/protocolSection/contactsLocationsModule/locations/7"
},
{
"op": "add",
"path": "/protocolSection/contactsLocationsModule/locations/23",
"value": {
"zip": "277-8577",
"city": "Kashiwa",
"state": "Chiba",
"status": "RECRUITING",
"country": "Japan",
"contacts": [
{
"name": "Makoto Tahara",
"role": "CONTACT"
}
],
"facility": "National Cancer Center Hospital East",
"geoPoint": {
"lat": 35.86224,
"lon": 139.97732
}
}
}
]