evt_NCT00128856_v2_v3_8ef69dd7738a

{
  "changed_paths": [
    "/protocolSection/statusModule/statusVerifiedDate",
    "/protocolSection/statusModule/lastUpdateSubmitDate",
    "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "/protocolSection/descriptionModule/briefSummary",
    "/protocolSection/armsInterventionsModule/armGroups/0/description",
    "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/0",
    "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/1",
    "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/2",
    "/protocolSection/armsInterventionsModule/interventions/0/name",
    "/protocolSection/armsInterventionsModule/interventions/0/otherNames/0",
    "/protocolSection/armsInterventionsModule/interventions/0/otherNames/1",
    "/protocolSection/armsInterventionsModule/interventions/1",
    "/protocolSection/armsInterventionsModule/interventions/2",
    "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
    "/protocolSection/outcomesModule/primaryOutcomes/0/description",
    "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/0/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/4/description",
    "/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
    "/protocolSection/outcomesModule/secondaryOutcomes/5",
    "/protocolSection/eligibilityModule/eligibilityCriteria",
    "/protocolSection/referencesModule/seeAlsoLinks/0/label"
  ],
  "citation_text": "TrialDiff Evidence Record evt_NCT00128856_v2_v3_8ef69dd7738a. ClinicalTrials.gov NCT00128856, versions 2-3. 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 2 to version 3 for NCT00128856.",
    "The JSON Patch for this comparison has hash 51476d808283d70fe5b01bb0c08edc7282a9e07b148688bca6f3dfb91a343ef9.",
    "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, secondary_outcome_removed_after_primary_completion.",
    "A registry field under the primary outcome module changed between ClinicalTrials.gov versions 2 and 3.",
    "The timing context for the from-version record was post_recruitment.",
    "The deterministic rules that fired were: arms_or_interventions_change, eligibility_criteria_change, primary_outcome_any_change, secondary_outcome_any_change.",
    "The changed JSON Pointer paths were: /protocolSection/statusModule/statusVerifiedDate, /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/descriptionModule/briefSummary, /protocolSection/armsInterventionsModule/armGroups/0/description, /protocolSection/armsInterventionsModule/armGroups/0/interventionNames/0, /protocolSection/armsInterventionsModule/armGroups/0/interventionNames/1, /protocolSection/armsInterventionsModule/armGroups/0/interventionNames/2, /protocolSection/armsInterventionsModule/interventions/0/name, /protocolSection/armsInterventionsModule/interventions/0/otherNames/0, /protocolSection/armsInterventionsModule/interventions/0/otherNames/1, /protocolSection/armsInterventionsModule/interventions/1, /protocolSection/armsInterventionsModule/interventions/2, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/primaryOutcomes/0/description, /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/0/measure, /protocolSection/outcomesModule/secondaryOutcomes/0/description, /protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/1/description, /protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/2/measure, /protocolSection/outcomesModule/secondaryOutcomes/2/description, /protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/4/measure, /protocolSection/outcomesModule/secondaryOutcomes/4/description, /protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/5, /protocolSection/eligibilityModule/eligibilityCriteria, /protocolSection/referencesModule/seeAlsoLinks/0/label.",
    "A primary outcome definition field changed after primary completion between versions 2 and 3, without a results-posting co-occurrence signal.",
    "The JSON Patch removed a whole secondary outcome item after primary completion between versions 2 and 3; when a TO-version outcome list is available, reindex-only removals are excluded."
  ],
  "classification": {
    "calibration_status": "uncalibrated",
    "categories": [
      "primary_outcome_change",
      "arm_intervention_change",
      "secondary_outcome_change",
      "eligibility_change"
    ],
    "category": "primary_outcome_change",
    "deterministic_rules": [
      "arms_or_interventions_change",
      "eligibility_criteria_change",
      "primary_outcome_any_change",
      "secondary_outcome_any_change"
    ],
    "event_class_rule_set_hash": "07957f8b90549d4f42387f51b471ecde9901b6db63bbc27b84c73631603407c0",
    "event_classes": [
      "primary_endpoint_changed_after_primary_completion_without_results_reconciliation",
      "secondary_outcome_removed_after_primary_completion"
    ],
    "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_NCT00128856_v2_v3_8ef69dd7738a",
  "evidence_version": 1,
  "patch": [
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/statusVerifiedDate",
      "value": "2018-12"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
      "value": "2018-12-13"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
      "value": "2018-12-14"
    },
    {
      "op": "replace",
      "path": "/protocolSection/descriptionModule/briefSummary",
      "value": "This is a multicenter, open-label, phase II trial to assess the efficacy of the GAT neoadjuvant regimen in patients with stage III breast cancer."
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/armGroups/0/description",
      "value": "Neoadjuvant chemotherapy consisted of adriamycine 40 mg/m2, administered on day 1 as an i.v.\ninfusion.\nPaclitaxel 150 mg/m2 was administered on day 2 as an i.v infusion followed by gemcitabine 2000 mg/m2 as an i.v.\ninfusion.\nThe three drugs were administered every two weeks for 6 cycles."
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/0",
      "value": "Drug: Gemcitabine"
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/1",
      "value": "Drug: Adriamycine"
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/2",
      "value": "Drug: Paclitaxel"
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/interventions/0/name",
      "value": "Gemcitabine"
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/interventions/0/otherNames/0",
      "value": "Gemzar"
    },
    {
      "op": "remove",
      "path": "/protocolSection/armsInterventionsModule/interventions/0/otherNames/1"
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/interventions/1",
      "value": {
        "armGroupLabels": [
          "Gemcitabine + Adriamycine + Paclitaxel"
        ],
        "name": "Adriamycine",
        "otherNames": [
          "doxorubicin"
        ],
        "type": "DRUG"
      }
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/interventions/2",
      "value": {
        "armGroupLabels": [
          "Gemcitabine + Adriamycine + Paclitaxel"
        ],
        "name": "Paclitaxel",
        "otherNames": [
          "Taxol"
        ],
        "type": "DRUG"
      }
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
      "value": "Pathological complete response (pCR) rate"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/description",
      "value": "pCR is defined as no invasive cells identifiable in breast sections at surgery.\nResponse will be measured by physical exam and breast imaging before surgery and will be evaluated according to the World Health Organization (WHO) criteria.\nPathological response after surgery, will be based on the proportion of remaining tumor and post-chemotherapy changes, evaluating separately the response in the breast and in the axilla lymph nodes."
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
      "value": "Up to week 15"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/measure",
      "value": "Overall response rate (ORR)"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/description",
      "value": "Tumor response is defined as the percentage of patients with a complete or partial response out of the patients who had measurable disease at baseline."
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
      "value": "Up to week 12"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
      "value": "To determine the percentage of conservative surgery rate versus other surgery"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
      "value": "Up to week 15"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
      "value": "The Number of Participants Who Experienced Adverse Events (AE)"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
      "value": "According to the Common Terminology Criteria for Adverse Events (CTCAE) version 2.0"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
      "value": "Through study treatment up to surgery"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
      "value": "Up to 5 years since surgery"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
      "value": "Tissue molecular markers and their correlation with response"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/4/description",
      "value": "Evaluation of changes in the tumor marker profile before and after treatment in tumor samples obtained before and after chemotherapy treatment."
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
      "value": "Up to week 15"
    },
    {
      "op": "remove",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/5"
    },
    {
      "op": "replace",
      "path": "/protocolSection/eligibilityModule/eligibilityCriteria",
      "value": "<p>Inclusion Criteria:</p><ul><li>Stage III breast cancer disease, with histological confirmation by true-cut or open-biopsy.</li><li>Ages between 18 and 75 years old.\nPatients older than 70 must have an adequate quality of life to be eligible.</li><li>Patients cannot have received previous treatment with chemotherapy, hormone therapy, radiotherapy or immune therapy.</li><li>Performance status of 0,1, 2 Eastern Cooperative Oncology Group (ECOG).</li><li>At least a 6 month life expectancy.</li><li>Neutrophils &gt; 1500; platelets &gt; 100000; haemoglobin &gt; 10 mg&#x2F;dL.</li><li>Adequate renal and hepatic functions, with serum creatinine &lt; 1.2 mg&#x2F;dl and total bilirubin &lt; 2 mg&#x2F;dl.</li><li>Adequate contraceptive methods during the study and up to 3 months after.</li><li>Adequate cardiac function assessed by physical exam, electrocardiogram and left ventricular ejection fraction &gt; 55%.</li></ul><p>Exclusion Criteria:</p><ul><li>Inflammatory carcinoma or stage I, II or IV breast cancer disease.</li><li>Males.</li><li>Active infection.</li><li>Other neoplasms except for basal skin carcinoma or cervical in situ carcinoma adequately treated.\nOther previous neoplasms are allowed if diagnosed and treated more than 5 years before study registration.</li><li>Concomitant serious disease provoking organ failure (heart, renal, hepatic, respiratory).</li><li>Pre-existing motor or sensorial neuropathy &gt; grade 1.</li><li>Inability for treatment compliance.</li><li>History of hypersensitivity to compounds such as cremophor, cyclosporine or vitamin K.</li><li>History of arrhythmias or congestive heart failure, even when controlled; or active cardiac blocking of second or third grade.</li><li>History of myocardial infarction in the previous 6 months.</li><li>Hypertension not controlled.</li><li>Pregnant or lactating women.</li></ul>"
    },
    {
      "op": "replace",
      "path": "/protocolSection/referencesModule/seeAlsoLinks/0/label",
      "value": "Description Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group"
    }
  ],
  "provenance": {
    "from_snapshot_hash": "760ce615ba133d181ac175f8d61006e9a664152d60908829283bf834f776ca20",
    "materiality_event_hash": "919b50f0f3f5887f2dadea467c94f93a3d8f0b4a89cf0be171cc29c3bd7a2936",
    "patch_hash": "51476d808283d70fe5b01bb0c08edc7282a9e07b148688bca6f3dfb91a343ef9",
    "patch_raw_hash": "1f2fcba2c6da3227859b70886e0361fa29a1caed86363a36a5f84c187cf2353c",
    "patch_source": "ctgov_internal_history",
    "patch_source_url": "https://clinicaltrials.gov/api/int/studies/NCT00128856/history/2?patchToVersion=3",
    "to_snapshot_hash": "d30ca9d431eb564fc86ba20f4696766a5b004a683ba9b70a7d2d7becaa60d5ee"
  },
  "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/NCT00128856",
    "nct_id": "NCT00128856"
  },
  "versions": {
    "from_version": 2,
    "submitted_date": "2018-12-13",
    "to_version": 3
  }
}