evt_NCT02154529_v21_v22_92760ebc54f9

{
  "changed_paths": [
    "/protocolSection/statusModule/statusVerifiedDate",
    "/protocolSection/statusModule/whyStopped",
    "/protocolSection/statusModule/lastUpdateSubmitDate",
    "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "/protocolSection/designModule/designInfo/interventionModel",
    "/protocolSection/designModule/designInfo/interventionModelDescription",
    "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/3/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/4",
    "/protocolSection/outcomesModule/secondaryOutcomes/5",
    "/protocolSection/outcomesModule/otherOutcomes/0/description",
    "/protocolSection/outcomesModule/otherOutcomes/1",
    "/annotationSection"
  ],
  "citation_text": "TrialDiff Evidence Record evt_NCT02154529_v21_v22_92760ebc54f9. ClinicalTrials.gov NCT02154529, versions 21-22. 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 the outcome change was inconsistent with the protocol or statistical analysis plan.",
    "That event-class membership is a validated global review-priority ranking."
  ],
  "claims_supported": [
    "TrialDiff compared ClinicalTrials.gov record version 21 to version 22 for NCT02154529.",
    "The JSON Patch for this comparison has hash e8aa192373735988fd69d034c2d56cdd203f1e2dd600eef148b39a60c1cef4ec.",
    "The active deterministic rule set hash was 318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86.",
    "The deterministic triage label was critical; before timing adjustment it was critical.",
    "The triage label is uncalibrated metadata, not a validated review-priority finding.",
    "The patch satisfied these deterministic event-class predicates: primary_endpoint_changed_after_primary_completion_without_results_reconciliation.",
    "A registry field under the primary outcome module changed between ClinicalTrials.gov versions 21 and 22.",
    "The timing context for the from-version record was post_recruitment.",
    "The deterministic rules that fired were: design_info_change, primary_outcome_any_change, secondary_outcome_any_change, why_stopped_change.",
    "The changed JSON Pointer paths were: /protocolSection/statusModule/statusVerifiedDate, /protocolSection/statusModule/whyStopped, /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/designModule/designInfo/interventionModel, /protocolSection/designModule/designInfo/interventionModelDescription, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/secondaryOutcomes/0/measure, /protocolSection/outcomesModule/secondaryOutcomes/1/measure, /protocolSection/outcomesModule/secondaryOutcomes/1/description, /protocolSection/outcomesModule/secondaryOutcomes/2/measure, /protocolSection/outcomesModule/secondaryOutcomes/2/description, /protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/3/measure, /protocolSection/outcomesModule/secondaryOutcomes/3/description, /protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/4, /protocolSection/outcomesModule/secondaryOutcomes/5, /protocolSection/outcomesModule/otherOutcomes/0/description, /protocolSection/outcomesModule/otherOutcomes/1, /annotationSection.",
    "A primary outcome definition field changed after primary completion between versions 21 and 22, without a results-posting co-occurrence signal.",
    "The changed paths include the ClinicalTrials.gov whyStopped field, a stopped-trial explanation field relevant to 42 CFR 11.64 when applicable."
  ],
  "classification": {
    "calibration_status": "uncalibrated",
    "categories": [
      "primary_outcome_change",
      "design_change",
      "status_termination",
      "secondary_outcome_change"
    ],
    "category": "primary_outcome_change",
    "deterministic_rules": [
      "design_info_change",
      "primary_outcome_any_change",
      "secondary_outcome_any_change",
      "why_stopped_change"
    ],
    "event_class_rule_set_hash": "07957f8b90549d4f42387f51b471ecde9901b6db63bbc27b84c73631603407c0",
    "event_classes": [
      "primary_endpoint_changed_after_primary_completion_without_results_reconciliation"
    ],
    "rule_set_hash": "318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86",
    "severity": "critical",
    "severity_pre_timing": "critical",
    "timing_context": "post_recruitment",
    "triage_label": "critical",
    "triage_rule_set_hash": "af5e5835e00a5fcfe2a17fd02b5fc244c2564104f93f78a1d77d7889f12a178b",
    "value_signals": []
  },
  "event_id": "evt_NCT02154529_v21_v22_92760ebc54f9",
  "evidence_version": 1,
  "patch": [
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/statusVerifiedDate",
      "value": "2021-05"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/whyStopped",
      "value": "Sponsor closed the study due to lack of response."
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
      "value": "2021-05-07"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
      "value": "2021-05-12"
    },
    {
      "op": "replace",
      "path": "/protocolSection/designModule/designInfo/interventionModel",
      "value": "PARALLEL"
    },
    {
      "op": "add",
      "path": "/protocolSection/designModule/designInfo/interventionModelDescription",
      "value": "Part 1 is a phase 1b ascending dose-finding study for establishing the maximum tolerated dose (MTD) of tesevatinib (with trastuzumab).\nPart 2 is a phase 2a expansion study with subjects assigned to 1 of 3 parallel groups who were administered the MTD of tesevatinib (with trastuzumab)."
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
      "value": "Safety: Number of Subjects Experiencing Adverse Events as a Measure of Safety and Tolerability and MTD"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
      "value": "Efficacy: Response Rate"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
      "value": "Efficacy: Median Progression-Free Survival"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
      "value": "To determine the median progression-free survival (PFS) and the percentage of subjects without disease progression after 2, 4, and 6 months of dosing."
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
      "value": "Efficacy: Median Overall Survival"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
      "value": "To determine the median overall survival (OS)."
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
      "value": "30 months"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/measure",
      "value": "Pharmacokinetics: Cmax"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/description",
      "value": "To evaluate the following pharmacokinetic parameter maximum concentration (Cmax) for the combination of tesevatinib and trastuzumab.\nPlasma concentrations of tesevatinib and serum concentrations of trastuzumab will be summarized by dose, sample collection day, and sample collection time for each drug."
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
      "value": "27 months"
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/4",
      "value": {
        "description": "To evaluate the following PK parameter time of maximum concentration (Tmax) for the combination of tesevatinib and trastuzumab.\nPlasma concentrations of tesevatinib and serum concentrations of trastuzumab will be summarized by dose, sample collection day, and sample collection time for each drug.",
        "measure": "Pharmacokinetics: Tmax",
        "timeFrame": "27 months"
      }
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/5",
      "value": {
        "description": "To evaluate the following PK parameter area under concentration curve from 0 to 24 hours (AUC[0-24hr]) for the combination of tesevatinib and trastuzumab.\nPlasma concentrations of tesevatinib and serum concentrations of trastuzumab will be summarized by dose, sample collection day, and sample collection time for each drug.",
        "measure": "Pharmacokinetics: AUC(0-24)",
        "timeFrame": "27 months"
      }
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/otherOutcomes/0/description",
      "value": "Efficacy: To evaluate changes in neurologic symptoms in subjects with leptomeningeal metastases.\nThis outcome measure is specific to subjects with leptomeningeal metastases (Phase 2a, Group 3)."
    },
    {
      "op": "remove",
      "path": "/protocolSection/outcomesModule/otherOutcomes/1"
    },
    {
      "op": "add",
      "path": "/annotationSection",
      "value": {
        "annotationModule": {
          "unpostedAnnotation": {
            "unpostedEvents": [
              {
                "date": "2022-01-04",
                "type": "RELEASE"
              },
              {
                "date": "2022-02-01",
                "type": "RESET"
              }
            ],
            "unpostedResponsibleParty": "Kadmon Corporation, LLC"
          }
        }
      }
    }
  ],
  "provenance": {
    "from_snapshot_hash": "6d8554cf25e88ac3132a505f4ac72783294f1e09209af7a754383010e6f597b2",
    "materiality_event_hash": "f503bf9f7dad17f1dc0421b1e5ec08e1bec83357227807bd64248ca017ab73b5",
    "patch_hash": "e8aa192373735988fd69d034c2d56cdd203f1e2dd600eef148b39a60c1cef4ec",
    "patch_raw_hash": "eff1129c61422ecd4f5295f33e4e49facf0cd19738f338f888f3538c89780bea",
    "patch_source": "ctgov_internal_history",
    "patch_source_url": "https://clinicaltrials.gov/api/int/studies/NCT02154529/history/21?patchToVersion=22",
    "to_snapshot_hash": "8f9847ffe93d262a32e48a63afae14d55fac5b1dd7b79038ff99e18063384baa"
  },
  "review_question": "What did the primary outcome field say before and after the amendment, and is there a public protocol, statistical analysis plan, or manuscript explaining the change?",
  "schema": "trialdiff.evidence_record",
  "trial": {
    "clinicaltrials_gov_url": "https://clinicaltrials.gov/study/NCT02154529",
    "nct_id": "NCT02154529"
  },
  "versions": {
    "from_version": 21,
    "submitted_date": "2021-05-07",
    "to_version": 22
  }
}