Evidence Record
evt_NCT05243641_v13_v14_f14bc034bb4f
NCT05243641 · Neratinib and Capmatinib Combination (Phase Ib/II) in Metastatic Breast Cancer and Inflammatory Breast Cancer Patients With Abnormal HER-family and c-Met Pathway Activity as Measured by the CELsignia Signaling Analysis Test
Superseded Evidence Record
This page preserves the immutable v0.1.2 record. Its current successor is evt_NCT05243641_v13_v14_69f9005d9a48.
Severity is deterministic, reproducible, uncalibrated triage metadata, not validated review priority or proven wrongdoing. This page states what the registry evidence supports and what it does not support.
Triage severity
Triage: Low Category
Results Reconciliation
Versions
v13 to v14
Timing
Post Recruitment
Claims Supported
- TrialDiff compared ClinicalTrials.gov record version 13 to version 14 for NCT05243641.
- The JSON Patch for this comparison has hash 1fb4a12983cf170d07941ea54205c02175b6eef0e82d7e0a7fc5e6b16fe6b9d7.
- The active deterministic rule set hash was 318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86.
- The deterministic triage label was low; before timing adjustment it was low.
- The triage label is uncalibrated metadata, not a validated review-priority finding.
- The patch satisfied these deterministic event-class predicates: outcome_edit_cooccurs_with_results_posting.
- The timing context for the from-version record was post_recruitment.
- The changed JSON Pointer paths were: /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/statusModule/resultsFirstSubmitDate, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/0/description, /protocolSection/outcomesModule/primaryOutcomes/1/measure, /protocolSection/outcomesModule/primaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/1/description, /protocolSection/outcomesModule/secondaryOutcomes, /documentSection/largeDocumentModule/largeDocs/0, /hasResults, /resultsSection, /annotationSection.
- An outcome path changed between versions 13 and 14 in a patch that also carried a hasResults or resultsSection co-occurrence signal.
Claims Not Supported
- That the amendment was scientifically unjustified.
- That the change constitutes misconduct or wrongdoing.
- That sponsor intent can be inferred from this registry change.
- That the change caused or altered the trial's results.
- That the change was or was not disclosed in a manuscript.
- That TrialDiff determines regulatory compliance or non-compliance.
- That co-occurrence with results posting proves the outcome edit was harmless, administrative, or substantively benign.
- That event-class membership is a validated global review-priority ranking.
Neutral Review Question
What source document explains this registry amendment, and does it change interpretation of the trial record?
Citation
TrialDiff Evidence Record evt_NCT05243641_v13_v14_f14bc034bb4f. ClinicalTrials.gov NCT05243641, versions 13-14. Evidence version 1.
Event Classes
outcome_edit_cooccurs_with_results_posting Changed Paths
/protocolSection/statusModule/lastUpdateSubmitDate
/protocolSection/statusModule/lastUpdatePostDateStruct/date
/protocolSection/statusModule/resultsFirstSubmitDate
/protocolSection/outcomesModule/primaryOutcomes/0/measure
/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame
/protocolSection/outcomesModule/primaryOutcomes/0/description
/protocolSection/outcomesModule/primaryOutcomes/1/measure
/protocolSection/outcomesModule/primaryOutcomes/1/timeFrame
/protocolSection/outcomesModule/primaryOutcomes/1/description
/protocolSection/outcomesModule/secondaryOutcomes
/documentSection/largeDocumentModule/largeDocs/0
/hasResults
/resultsSection
/annotationSection
View the field-level diff for before/after values on each changed path.
Deterministic Rules
No deterministic rules recorded.
Provenance
- Package generation
v0.1.2- Succeeded by
- evt_NCT05243641_v13_v14_69f9005d9a48
- Patch hash
1fb4a12983cf170d07941ea54205c02175b6eef0e82d7e0a7fc5e6b16fe6b9d7- Canonical hash
1029bed99f01dfae97139e6b75f9bf020bca60795215506debdd736f6fdf2dd8- Rule set hash
318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86- From snapshot
9d606583e01e984dc90a596f210bc12fb6c10be85c475a7f6abf54a296e21ea0- To snapshot
c9d4fa5594cbe378899b91730232a0761df597c4901e49e4db17f9b22946635a- Patch source
- ctgov_internal_history
- Generated at
- 2026-07-31T00:42:12.000Z
- Source URL
- Registry payload
Canonical JSON Preview
Stored payload{
"changed_paths": [
"/protocolSection/statusModule/lastUpdateSubmitDate",
"/protocolSection/statusModule/lastUpdatePostDateStruct/date",
"/protocolSection/statusModule/resultsFirstSubmitDate",
"/protocolSection/outcomesModule/primaryOutcomes/0/measure",
"/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/0/description",
"/protocolSection/outcomesModule/primaryOutcomes/1/measure",
"/protocolSection/outcomesModule/primaryOutcomes/1/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/1/description",
"/protocolSection/outcomesModule/secondaryOutcomes",
"/documentSection/largeDocumentModule/largeDocs/0",
"/hasResults",
"/resultsSection",
"/annotationSection"
],
"citation_text": "TrialDiff Evidence Record evt_NCT05243641_v13_v14_f14bc034bb4f. ClinicalTrials.gov NCT05243641, versions 13-14. Evidence version 1.",
"claims_not_supported": [
"That the amendment was scientifically unjustified.",
"That the change constitutes misconduct or wrongdoing.",
"That sponsor intent can be inferred from this registry change.",
"That the change caused or altered the trial's results.",
"That the change was or was not disclosed in a manuscript.",
"That TrialDiff determines regulatory compliance or non-compliance.",
"That co-occurrence with results posting proves the outcome edit was harmless, administrative, or substantively benign.",
"That event-class membership is a validated global review-priority ranking."
],
"claims_supported": [
"TrialDiff compared ClinicalTrials.gov record version 13 to version 14 for NCT05243641.",
"The JSON Patch for this comparison has hash 1fb4a12983cf170d07941ea54205c02175b6eef0e82d7e0a7fc5e6b16fe6b9d7.",
"The active deterministic rule set hash was 318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86.",
"The deterministic triage label was low; before timing adjustment it was low.",
"The triage label is uncalibrated metadata, not a validated review-priority finding.",
"The patch satisfied these deterministic event-class predicates: outcome_edit_cooccurs_with_results_posting.",
"The timing context for the from-version record was post_recruitment.",
"The changed JSON Pointer paths were: /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/statusModule/resultsFirstSubmitDate, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/0/description, /protocolSection/outcomesModule/primaryOutcomes/1/measure, /protocolSection/outcomesModule/primaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/1/description, /protocolSection/outcomesModule/secondaryOutcomes, /documentSection/largeDocumentModule/largeDocs/0, /hasResults, /resultsSection, /annotationSection.",
"An outcome path changed between versions 13 and 14 in a patch that also carried a hasResults or resultsSection co-occurrence signal."
],
"classification": {
"calibration_status": "uncalibrated",
"categories": [
"results_reconciliation"
],
"category": "results_reconciliation",
"deterministic_rules": [],
"event_class_rule_set_hash": "07957f8b90549d4f42387f51b471ecde9901b6db63bbc27b84c73631603407c0",
"event_classes": [
"outcome_edit_cooccurs_with_results_posting"
],
"rule_set_hash": "318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86",
"severity": "low",
"severity_pre_timing": "low",
"timing_context": "post_recruitment",
"triage_label": "low",
"triage_rule_set_hash": "af5e5835e00a5fcfe2a17fd02b5fc244c2564104f93f78a1d77d7889f12a178b",
"value_signals": [
{
"category": "results_reconciliation",
"paths": [
"/protocolSection/outcomesModule/primaryOutcomes/0/description",
"/protocolSection/outcomesModule/primaryOutcomes/0/measure",
"/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/1/description",
"/protocolSection/outcomesModule/primaryOutcomes/1/measure",
"/protocolSection/outcomesModule/primaryOutcomes/1/timeFrame"
],
"severity": "low",
"signal": "results_reconciliation_outcome_suppression"
}
]
},
"event_id": "evt_NCT05243641_v13_v14_f14bc034bb4f",
"evidence_version": 1,
"patch": [
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdateSubmitDate",
"value": "2025-01-28"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
"value": "2025-03-25"
},
{
"op": "add",
"path": "/protocolSection/statusModule/resultsFirstSubmitDate",
"value": "2025-01-28"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
"value": "To Determine Maximum Tolerated Dose for Use in the Phase II Portion of the Trial"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
"value": "Cycle1 and 2, total 56 days"
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/description",
"value": "This phase of the study uses the Bayesian Optimal Interval (BOIN) design with a 3+3 run-in to identify the maximum tolerable dose (MTD).\nPatients are treated in cohorts of 3 with a maximum of 27 participants.\nStarting with Neratinib PO dose level 1 (120 mg for Dose 1-7, then 160 mg) combined with Capmatinib PO level 1 (400 mg), with up to 12 patients per dose.\nThe target toxicity rate for the MTD is 25%."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/1/measure",
"value": "To Determine Overall Response Rate (ORR: CR+PR)"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/1/timeFrame",
"value": "Up to 3 years"
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/primaryOutcomes/1/description",
"value": "To assess the overall response rate (ORR) for patients treated at the MTD."
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/secondaryOutcomes",
"value": [
{
"description": "AEs (CTCAE version 5.0) ≥ grade 2 non-hematological and ≥ grade 3 hematological, occurring after the first protocol intervention observed.",
"measure": "To Further Characterize the Safety and Tolerability of Neratinib + Capmatinib",
"timeFrame": "Up to 3 years"
},
{
"description": "Clinical benefit rate (CBR) is defined as the rate of patients who achieved complete response, partial response and stable disease for ≥ 24 weeks.",
"measure": "To Determine Clinical Benefit Rate (CBR)",
"timeFrame": "Up to 3 years"
},
{
"description": "Duration of response (DOR) is defined as the period from the date of the first occurrence of a CR or PR until the first date that progressive disease or death is documented.",
"measure": "To Determine the Duration of Response (DOR)",
"timeFrame": "Up to 3 years"
},
{
"description": "PFS is defined as the time between date of treatment start to the date of documented disease progression or death, whichever occurs first",
"measure": "To Determine Progression Free Survival (PFS)",
"timeFrame": "Up to 3 years"
},
{
"description": "The proportion of patients in the study who are alive 2 years after enrollment on to the study",
"measure": "To Determine 2 Year Overall Survival (OS)",
"timeFrame": "2 years after enrollment"
}
]
},
{
"op": "add",
"path": "/documentSection/largeDocumentModule/largeDocs/0",
"value": {
"date": "2024-02-01",
"filename": "Prot_SAP_001.pdf",
"hasIcf": false,
"hasProtocol": true,
"hasSap": true,
"label": "Study Protocol and Statistical Analysis Plan",
"size": 2345255,
"typeAbbrev": "Prot_SAP",
"uploadDate": "2025-01-07T11:52"
}
},
{
"op": "replace",
"path": "/hasResults",
"value": true
},
{
"op": "add",
"path": "/resultsSection",
"value": {
"adverseEventsModule": {
"armsReviewUnit": {
"resetReasons": [
"The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided."
]
},
"description": "Death or life-threatening events that are unexpected, possibly, probably or definitely related to drug must be reported (initial or follow up) to the IND Office within 24 hours of knowledge of the event",
"eventGroups": [
{
"deathsNumAffected": 1,
"deathsNumAtRisk": 10,
"description": "Dose Escalation of Neratinib with Capmatinib uses a 3+3 design.\nMax 18 patients, treated in cohorts of 3, with safety data reviewed after each cohort's DLT period.",
"id": "EG000",
"otherNumAffected": 10,
"otherNumAtRisk": 10,
"seriousNumAffected": 2,
"seriousNumAtRisk": 10,
"title": "Phase Ib"
},
{
"deathsNumAffected": 0,
"deathsNumAtRisk": 0,
"description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used.",
"id": "EG001",
"otherNumAffected": 0,
"otherNumAtRisk": 0,
"seriousNumAffected": 0,
"seriousNumAtRisk": 0,
"title": "Phase II"
}
],
"frequencyThreshold": "4",
"otherEvents": [
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Gastrointestinal disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 4,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Abdominal Pain"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Investigations",
"stats": [
{
"groupId": "EG000",
"numAffected": 4,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Alanine Aminotransferase Increased"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Metabolism and nutrition disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 4,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Anorexia"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Musculoskeletal and connective tissue disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 4,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Arthralgia"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Gastrointestinal disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 6,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Constipation"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Metabolism and nutrition disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 6,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Dehydration"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Gastrointestinal disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 8,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Diarrhea"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Nervous system disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 6,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Dizziness"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "General disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 9,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Fatigue"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Nervous system disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 4,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Headache"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Metabolism and nutrition disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 5,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Hypoalbuminemia"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Musculoskeletal and connective tissue disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 4,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Myalgia"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Gastrointestinal disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 8,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Nausea"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Investigations",
"stats": [
{
"groupId": "EG000",
"numAffected": 4,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Platelet Count Decreased"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Investigations",
"stats": [
{
"groupId": "EG000",
"numAffected": 4,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Serum Amylase Increased"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Gastrointestinal disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 6,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Vomiting"
}
],
"reviewUnit": {
"resetReasons": [
"There does not appear to be sufficient information to understand the Time Frame."
]
},
"seriousEvents": [
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Respiratory, thoracic and mediastinal disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 1,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Pneumothorax"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Metabolism and nutrition disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 1,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Hypoalbuminemia"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "General disorders",
"stats": [
{
"groupId": "EG000",
"numAffected": 1,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Disease Progression"
},
{
"assessmentType": "NON_SYSTEMATIC_ASSESSMENT",
"organSystem": "Infections and infestations",
"stats": [
{
"groupId": "EG000",
"numAffected": 1,
"numAtRisk": 10
},
{
"groupId": "EG001",
"numAtRisk": 0
}
],
"term": "Lung Infection"
}
],
"timeFrame": "Serious adverse events will be captured from the time of the first protocol-specific intervention, until 30 days after the last dose, unless the participant withdraws consent. Serious adverse events must be followed until clinical recovery is complete and laboratory tests have returned to baseline, progression of the event has stabilized, or there has been acceptable resolution of the event."
},
"baselineCharacteristicsModule": {
"denoms": [
{
"counts": [
{
"groupId": "BG000",
"value": "10"
},
{
"groupId": "BG001",
"value": "0"
},
{
"groupId": "BG002",
"value": "10"
}
],
"units": "Participants"
}
],
"groups": [
{
"description": "Dose Escalation of Neratinib with Capmatinib uses a 3+3 design.\nMax 18 patients, treated in cohorts of 3, with safety data reviewed after each cohort's DLT period.",
"id": "BG000",
"title": "Phase Ib"
},
{
"description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used.",
"id": "BG001",
"title": "Phase II"
},
{
"description": "Total of all reporting groups",
"id": "BG002",
"title": "Total"
}
],
"measures": [
{
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "BG000",
"lowerLimit": "39",
"upperLimit": "62",
"value": "44.5"
},
{
"groupId": "BG002",
"lowerLimit": "39",
"upperLimit": "62",
"value": "44.5"
}
]
}
]
}
],
"dispersionType": "FULL_RANGE",
"paramType": "MEDIAN",
"title": "Age, Continuous",
"unitOfMeasure": "Years"
},
{
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "BG000",
"value": "10"
},
{
"groupId": "BG002",
"value": "10"
}
],
"title": "Female"
},
{
"measurements": [
{
"groupId": "BG000",
"value": "0"
},
{
"groupId": "BG002",
"value": "0"
}
],
"title": "Male"
}
]
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"title": "Sex: Female, Male",
"unitOfMeasure": "Participants"
},
{
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "BG000",
"value": "2"
},
{
"groupId": "BG002",
"value": "2"
}
],
"title": "Hispanic or Latino"
},
{
"measurements": [
{
"groupId": "BG000",
"value": "8"
},
{
"groupId": "BG002",
"value": "8"
}
],
"title": "Not Hispanic or Latino"
},
{
"measurements": [
{
"groupId": "BG000",
"value": "0"
},
{
"groupId": "BG002",
"value": "0"
}
],
"title": "Unknown or Not Reported"
}
]
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"title": "Ethnicity (NIH/OMB)",
"unitOfMeasure": "Participants"
},
{
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "BG000",
"value": "0"
},
{
"groupId": "BG002",
"value": "0"
}
],
"title": "American Indian or Alaska Native"
},
{
"measurements": [
{
"groupId": "BG000",
"value": "0"
},
{
"groupId": "BG002",
"value": "0"
}
],
"title": "Asian"
},
{
"measurements": [
{
"groupId": "BG000",
"value": "0"
},
{
"groupId": "BG002",
"value": "0"
}
],
"title": "Native Hawaiian or Other Pacific Islander"
},
{
"measurements": [
{
"groupId": "BG000",
"value": "4"
},
{
"groupId": "BG002",
"value": "4"
}
],
"title": "Black or African American"
},
{
"measurements": [
{
"groupId": "BG000",
"value": "5"
},
{
"groupId": "BG002",
"value": "5"
}
],
"title": "White"
},
{
"measurements": [
{
"groupId": "BG000",
"value": "1"
},
{
"groupId": "BG002",
"value": "1"
}
],
"title": "More than one race"
},
{
"measurements": [
{
"groupId": "BG000",
"value": "0"
},
{
"groupId": "BG002",
"value": "0"
}
],
"title": "Unknown or Not Reported"
}
]
}
],
"paramType": "COUNT_OF_PARTICIPANTS",
"title": "Race (NIH/OMB)",
"unitOfMeasure": "Participants"
},
{
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "BG000",
"value": "10"
},
{
"groupId": "BG002",
"value": "10"
}
]
}
],
"title": "United States"
}
],
"paramType": "NUMBER",
"title": "Region of Enrollment",
"unitOfMeasure": "participants"
}
],
"populationDescription": "Baseline analysis population included all participants treated.\nThe study was terminated during phase Ib, resulting in no patient enrollment for phase II.",
"reviewUnit": {
"resetReasons": [
"The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided."
]
}
},
"moreInfoModule": {
"certainAgreement": {
"piSponsorEmployee": true
},
"pointOfContact": {
"email": "rlayman@mdanderson.org",
"organization": "M D Anderson Cancer Center",
"phone": "713) 745-8401",
"title": "Rachel M. Layman, MD"
}
},
"outcomeMeasuresModule": {
"outcomeMeasures": [
{
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"value": "9"
}
]
}
]
}
],
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "10"
}
],
"units": "Participants"
}
],
"description": "This phase of the study uses the Bayesian Optimal Interval (BOIN) design with a 3+3 run-in to identify the maximum tolerable dose (MTD).\nPatients are treated in cohorts of 3 with a maximum of 27 participants.\nStarting with Neratinib PO dose level 1 (120 mg for Dose 1-7, then 160 mg) combined with Capmatinib PO level 1 (400 mg), with up to 12 patients per dose.\nThe target toxicity rate for the MTD is 25%.",
"groups": [
{
"description": "Dose Escalation of Neratinib with Capmatinib uses a 3+3 design.\nMax 18 patients, treated in cohorts of 3, with safety data reviewed after each cohort's DLT period.",
"id": "OG000",
"title": "Phase Ib"
}
],
"measureCategoriesReviewUnit": {
"resetReasons": [
"The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided."
]
},
"paramType": "COUNT_OF_PARTICIPANTS",
"reportingStatus": "POSTED",
"timeFrame": "Cycle1 and 2, total 56 days",
"title": "To Determine Maximum Tolerated Dose for Use in the Phase II Portion of the Trial",
"type": "PRIMARY",
"unitOfMeasure": "Participants"
},
{
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "0"
}
],
"units": "Participants"
}
],
"description": "To assess the overall response rate (ORR) for patients treated at the MTD.",
"groups": [
{
"description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used.",
"id": "OG000",
"title": "Phase II"
}
],
"measureCategoriesReviewUnit": {
"resetReasons": [
"Required information appears to be missing."
]
},
"populationDescription": "No outcome measures were analyzed because Phase II was not conducted.",
"reportingStatus": "POSTED",
"timeFrame": "Up to 3 years",
"title": "To Determine Overall Response Rate (ORR: CR+PR)",
"type": "PRIMARY"
},
{
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "0"
}
],
"units": "Participants"
}
],
"description": "AEs (CTCAE version 5.0) ≥ grade 2 non-hematological and ≥ grade 3 hematological, occurring after the first protocol intervention observed.",
"groups": [
{
"description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used.",
"id": "OG000",
"title": "Phase II"
}
],
"measureCategoriesReviewUnit": {
"resetReasons": [
"Required information appears to be missing."
]
},
"populationDescription": "No outcome measures were analyzed because Phase II was not conducted.",
"reportingStatus": "POSTED",
"timeFrame": "Up to 3 years",
"title": "To Further Characterize the Safety and Tolerability of Neratinib + Capmatinib",
"type": "SECONDARY"
},
{
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "0"
}
],
"units": "Participants"
}
],
"description": "Clinical benefit rate (CBR) is defined as the rate of patients who achieved complete response, partial response and stable disease for ≥ 24 weeks.",
"groups": [
{
"description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used.",
"id": "OG000",
"title": "Phase II"
}
],
"measureCategoriesReviewUnit": {
"resetReasons": [
"Required information appears to be missing."
]
},
"populationDescription": "No outcome measures were analyzed because Phase II was not conducted.",
"reportingStatus": "POSTED",
"timeFrame": "Up to 3 years",
"title": "To Determine Clinical Benefit Rate (CBR)",
"type": "SECONDARY"
},
{
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "0"
}
],
"units": "Participants"
}
],
"description": "Duration of response (DOR) is defined as the period from the date of the first occurrence of a CR or PR until the first date that progressive disease or death is documented.",
"groups": [
{
"description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used.",
"id": "OG000",
"title": "Phase II"
}
],
"measureCategoriesReviewUnit": {
"resetReasons": [
"Required information appears to be missing."
]
},
"populationDescription": "No outcome measures were analyzed because Phase II was not conducted.",
"reportingStatus": "POSTED",
"timeFrame": "Up to 3 years",
"title": "To Determine the Duration of Response (DOR)",
"type": "SECONDARY"
},
{
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "0"
}
],
"units": "Participants"
}
],
"description": "PFS is defined as the time between date of treatment start to the date of documented disease progression or death, whichever occurs first",
"groups": [
{
"description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used.",
"id": "OG000",
"title": "Phase II"
}
],
"measureCategoriesReviewUnit": {
"resetReasons": [
"Required information appears to be missing."
]
},
"populationDescription": "No outcome measures were analyzed because Phase II was not conducted.",
"reportingStatus": "POSTED",
"timeFrame": "Up to 3 years",
"title": "To Determine Progression Free Survival (PFS)",
"type": "SECONDARY"
},
{
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "0"
}
],
"units": "Participants"
}
],
"description": "The proportion of patients in the study who are alive 2 years after enrollment on to the study",
"groups": [
{
"description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used.",
"id": "OG000",
"title": "Phase II"
}
],
"measureCategoriesReviewUnit": {
"resetReasons": [
"Required information appears to be missing."
]
},
"populationDescription": "No outcome measures were analyzed because Phase II was not conducted.",
"reportingStatus": "POSTED",
"timeFrame": "2 years after enrollment",
"title": "To Determine 2 Year Overall Survival (OS)",
"type": "SECONDARY"
}
]
},
"participantFlowModule": {
"groups": [
{
"description": "Dose Escalation of Neratinib with Capmatinib uses a 3+3 design.\nMax 18 patients, treated in cohorts of 3, with safety data reviewed after each cohort's DLT period.",
"id": "FG000",
"title": "Phase Ib"
},
{
"description": "Subjects receive neratinib and capmatinib.\nThe MTD determined during Phase Ib will be used.",
"id": "FG001",
"title": "Phase II"
}
],
"periods": [
{
"dropWithdraws": [
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "4"
},
{
"groupId": "FG001",
"numSubjects": "0"
}
],
"type": "Adverse Event"
},
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "6"
},
{
"groupId": "FG001",
"numSubjects": "0"
}
],
"type": "Disease progression"
}
],
"milestones": [
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "10"
},
{
"groupId": "FG001",
"numSubjects": "0"
}
],
"type": "STARTED"
},
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "0"
},
{
"groupId": "FG001",
"numSubjects": "0"
}
],
"type": "COMPLETED"
},
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "10"
},
{
"groupId": "FG001",
"numSubjects": "0"
}
],
"type": "NOT COMPLETED"
}
],
"reviewUnit": {
"resetReasons": [
"The participant flow appears to include insufficient information to understand the arms/groups to which participants were assigned, the intervention strategy used in each arm/group, or how participants progressed in the study."
]
},
"title": "Overall Study"
}
],
"preAssignmentDetails": "11 patients were accrued and assessed for eligibility and 10 patients were assigned to the cohort.",
"recruitmentDetails": "August 2022~ June 2023.\nAll recruitment was done at The University of Texas MD Anderson Cancer Center."
}
}
},
{
"op": "add",
"path": "/annotationSection",
"value": {
"annotationModule": {
"unpostedAnnotation": {
"unpostedEvents": [
{
"date": "2025-02-19",
"type": "RESET"
}
],
"unpostedResponsibleParty": "M.D. Anderson Cancer Center"
}
}
}
}
],
"provenance": {
"from_snapshot_hash": "9d606583e01e984dc90a596f210bc12fb6c10be85c475a7f6abf54a296e21ea0",
"materiality_event_hash": "7176558609d328a04299c218c37e641071a003d92984237f8920c0d41d4184bf",
"patch_hash": "1fb4a12983cf170d07941ea54205c02175b6eef0e82d7e0a7fc5e6b16fe6b9d7",
"patch_raw_hash": "37ab616ced0cf478454e57b54ce2785c8cee2f3cdb940b94ffdec0dc88b8acce",
"patch_source": "ctgov_internal_history",
"patch_source_url": "https://clinicaltrials.gov/api/int/studies/NCT05243641/history/13?patchToVersion=14",
"to_snapshot_hash": "c9d4fa5594cbe378899b91730232a0761df597c4901e49e4db17f9b22946635a"
},
"review_question": "What source document explains this registry amendment, and does it change interpretation of the trial record?",
"schema": "trialdiff.evidence_record",
"trial": {
"clinicaltrials_gov_url": "https://clinicaltrials.gov/study/NCT05243641",
"nct_id": "NCT05243641"
},
"versions": {
"from_version": 13,
"submitted_date": "2025-01-28",
"to_version": 14
}
}