evt_NCT02384239_v8_v9_a0da070bbb95

{
  "changed_paths": [
    "/protocolSection/statusModule/statusVerifiedDate",
    "/protocolSection/statusModule/startDateStruct/date",
    "/protocolSection/statusModule/lastUpdateSubmitDate",
    "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
    "/protocolSection/statusModule/resultsFirstSubmitDate",
    "/protocolSection/statusModule/resultsFirstSubmitQcDate",
    "/protocolSection/statusModule/resultsFirstPostDateStruct",
    "/protocolSection/sponsorCollaboratorsModule/collaborators",
    "/protocolSection/descriptionModule/briefSummary",
    "/protocolSection/descriptionModule/detailedDescription",
    "/protocolSection/armsInterventionsModule/armGroups/0/label",
    "/protocolSection/armsInterventionsModule/armGroups/0/description",
    "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/1",
    "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/2",
    "/protocolSection/armsInterventionsModule/armGroups/1/label",
    "/protocolSection/armsInterventionsModule/armGroups/1/description",
    "/protocolSection/armsInterventionsModule/armGroups/1/interventionNames/1",
    "/protocolSection/armsInterventionsModule/armGroups/1/interventionNames/2",
    "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/0",
    "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/1",
    "/protocolSection/armsInterventionsModule/interventions/0/description",
    "/protocolSection/armsInterventionsModule/interventions/1",
    "/protocolSection/armsInterventionsModule/interventions/2",
    "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
    "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
    "/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",
    "/protocolSection/outcomesModule/secondaryOutcomes/4",
    "/protocolSection/outcomesModule/secondaryOutcomes/5",
    "/annotationSection",
    "/hasResults",
    "/resultsSection",
    "/documentSection"
  ],
  "citation_text": "TrialDiff Evidence Record evt_NCT02384239_v8_v9_a0da070bbb95. ClinicalTrials.gov NCT02384239, versions 8-9. 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 8 to version 9 for NCT02384239.",
    "The JSON Patch for this comparison has hash 437a41d166c3290558adc37f01e3733284cc4d6931fbdf8059b2a3b9a70a02b8.",
    "The active deterministic rule set hash was fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621.",
    "The deterministic triage label was high; before timing adjustment it was high.",
    "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.",
    "A registry field under an arm or intervention module changed between ClinicalTrials.gov versions 8 and 9.",
    "The timing context for the from-version record was post_recruitment.",
    "The deterministic rules that fired were: arms_or_interventions_change.",
    "The changed JSON Pointer paths were: /protocolSection/statusModule/statusVerifiedDate, /protocolSection/statusModule/startDateStruct/date, /protocolSection/statusModule/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/statusModule/resultsFirstSubmitDate, /protocolSection/statusModule/resultsFirstSubmitQcDate, /protocolSection/statusModule/resultsFirstPostDateStruct, /protocolSection/sponsorCollaboratorsModule/collaborators, /protocolSection/descriptionModule/briefSummary, /protocolSection/descriptionModule/detailedDescription, /protocolSection/armsInterventionsModule/armGroups/0/label, /protocolSection/armsInterventionsModule/armGroups/0/description, /protocolSection/armsInterventionsModule/armGroups/0/interventionNames/1, /protocolSection/armsInterventionsModule/armGroups/0/interventionNames/2, /protocolSection/armsInterventionsModule/armGroups/1/label, /protocolSection/armsInterventionsModule/armGroups/1/description, /protocolSection/armsInterventionsModule/armGroups/1/interventionNames/1, /protocolSection/armsInterventionsModule/armGroups/1/interventionNames/2, /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/0, /protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/1, /protocolSection/armsInterventionsModule/interventions/0/description, /protocolSection/armsInterventionsModule/interventions/1, /protocolSection/armsInterventionsModule/interventions/2, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/secondaryOutcomes/1/measure, /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, /protocolSection/outcomesModule/secondaryOutcomes/4, /protocolSection/outcomesModule/secondaryOutcomes/5, /annotationSection, /hasResults, /resultsSection, /documentSection.",
    "The timeline value moved by 16 days.",
    "An outcome path changed between versions 8 and 9 in a patch that also carried a hasResults or resultsSection co-occurrence signal."
  ],
  "classification": {
    "calibration_status": "uncalibrated",
    "categories": [
      "arm_intervention_change",
      "timeline_actual_date_correction",
      "results_reconciliation"
    ],
    "category": "arm_intervention_change",
    "deterministic_rules": [
      "arms_or_interventions_change"
    ],
    "event_class_rule_set_hash": "74a6f55a686c29aa023171acd6b43f27ea95f2b0af2d49094ac70287ba4e502c",
    "event_classes": [
      "outcome_edit_cooccurs_with_results_posting"
    ],
    "rule_set_hash": "fc87f4f0a74bc789dbe4ba85893c2c96f55db62c22970be4e991288104291621",
    "severity": "high",
    "severity_pre_timing": "high",
    "timing_context": "post_recruitment",
    "triage_label": "high",
    "triage_rule_set_hash": "af5e5835e00a5fcfe2a17fd02b5fc244c2564104f93f78a1d77d7889f12a178b",
    "value_signals": [
      {
        "category": "timeline_actual_date_correction",
        "date_struct": "startDateStruct",
        "delta_days": 16,
        "direction": "earlier",
        "new_precision": "day",
        "new_type": "ACTUAL",
        "new_value": "2015-10-19",
        "old_precision": "day",
        "old_type": "ACTUAL",
        "old_value": "2015-11-04",
        "path": "/protocolSection/statusModule/startDateStruct/date",
        "severity": "low",
        "signal": "timeline_actual_date_correction"
      },
      {
        "category": "results_reconciliation",
        "paths": [
          "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
          "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
          "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
          "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
          "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
          "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
          "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
          "/protocolSection/outcomesModule/secondaryOutcomes/3",
          "/protocolSection/outcomesModule/secondaryOutcomes/4",
          "/protocolSection/outcomesModule/secondaryOutcomes/5"
        ],
        "severity": "low",
        "signal": "results_reconciliation_outcome_suppression"
      }
    ]
  },
  "event_id": "evt_NCT02384239_v8_v9_a0da070bbb95",
  "evidence_version": 1,
  "patch": [
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/statusVerifiedDate",
      "value": "2022-02"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/startDateStruct/date",
      "value": "2015-10-19"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdateSubmitDate",
      "value": "2022-02-16"
    },
    {
      "op": "replace",
      "path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
      "value": "2022-03-16"
    },
    {
      "op": "add",
      "path": "/protocolSection/statusModule/resultsFirstSubmitDate",
      "value": "2022-01-24"
    },
    {
      "op": "add",
      "path": "/protocolSection/statusModule/resultsFirstSubmitQcDate",
      "value": "2022-02-16"
    },
    {
      "op": "add",
      "path": "/protocolSection/statusModule/resultsFirstPostDateStruct",
      "value": {
        "date": "2022-03-16",
        "type": "ACTUAL"
      }
    },
    {
      "op": "add",
      "path": "/protocolSection/sponsorCollaboratorsModule/collaborators",
      "value": [
        {
          "class": "OTHER",
          "name": "Translational Breast Cancer Research Consortium"
        },
        {
          "class": "OTHER",
          "name": "Dana-Farber Cancer Institute"
        }
      ]
    },
    {
      "op": "replace",
      "path": "/protocolSection/descriptionModule/briefSummary",
      "value": "This phase II trial studies the side effects of palbociclib when given together with fulvestrant or tamoxifen citrate in treating patients with hormone receptor positive breast cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic).\nPalbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.\nHormone therapy using fulvestrant or tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells.\nGiving palbociclib together with fulvestrant or tamoxifen citrate may work better in treating hormone receptor positive breast cancer."
    },
    {
      "op": "add",
      "path": "/protocolSection/descriptionModule/detailedDescription",
      "value": "<p>Patients will be randomly allocated in a 1:1 ratio to take either 100 mg or 125 mg of palbociclib.\nRandomized treatment assignments will be made by permuted blocks, generated by our collaborating statistician at Dana-Farber Cancer Institute.</p><p>PRIMARY OBJECTIVES:</p><p>I. To evaluate the incidence of grade 3&#x2F;4 neutropenia in patients with hormone receptor positive (HR+) advanced breast cancer previously exposed to chemotherapy, treated with fulvestrant or tamoxifen (tamoxifen citrate) in combination with palbociclib at a dose of 100mg or 125mg.</p><p>SECONDARY OBJECTIVES:</p><p>I. To evaluate progression-free survival with 100 mg and 125 mg dosing of palbociclib.</p><p>II.\nTo evaluate inhibition of retinoblastoma (RB) phosphorylation in tumor and in skin at 100 mg and 125 mg dosing of palbociclib.</p><p>III.\nTo evaluate the correlation between inhibition of RB phosphorylation in skin and tumor.</p><p>IV.\nTo evaluate the correlation between inhibition of RB phosphorylation and progression-free survival (PFS).</p><p>V. To evaluate the objective response and clinical benefit rate of palbociclib given at 100 mg or 125 mg.</p><p>VI.\nTo evaluate the toxicity associated with palbociclib given at 100 mg and 125 mg in combination with fulvestrant or tamoxifen.</p><p>VII.\nTo evaluate markers of resistance to palbociclib and fulvestrant or tamoxifen in circulating plasma tumor deoxyribonucleic acid (DNA) (ptDNA).</p><p>OUTLINE: Patients are randomized to 1 of 2 treatment arms.</p><p>ARM I: Patients receive low-dose palbociclib orally (PO) on days 1-21.\nPatients also receive tamoxifen citrate PO on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1 and then on day 1 only in subsequent cycles.\nCycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</p><p>ARM II: Patients receive high-dose palbociclib PO on days 1-21.\nPatients also receive tamoxifen citrate PO on days 1-28 or fulvestrant IM on days 1 and 15 of cycle 1 and then on day 1 only in subsequent cycles.\nCycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</p>"
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/armGroups/0/label",
      "value": "Palbociclib 100mg and, fulvestrant or tamoxifen"
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/armGroups/0/description",
      "value": "Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)"
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/1",
      "value": "Drug: Tamoxifen"
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/armGroups/0/interventionNames/2",
      "value": "Drug: Fulvestrant"
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/armGroups/1/label",
      "value": "Palbociclib 125mg and, fulvestrant or tamoxifen"
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/armGroups/1/description",
      "value": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)"
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/armGroups/1/interventionNames/1",
      "value": "Drug: Tamoxifen"
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/armGroups/1/interventionNames/2",
      "value": "Drug: Fulvestrant"
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/0",
      "value": "Palbociclib 100mg and, fulvestrant or tamoxifen"
    },
    {
      "op": "replace",
      "path": "/protocolSection/armsInterventionsModule/interventions/0/armGroupLabels/1",
      "value": "Palbociclib 125mg and, fulvestrant or tamoxifen"
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/interventions/0/description",
      "value": "Given orally (PO)"
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/interventions/1",
      "value": {
        "armGroupLabels": [
          "Palbociclib 100mg and, fulvestrant or tamoxifen",
          "Palbociclib 125mg and, fulvestrant or tamoxifen"
        ],
        "description": "Given orally (PO)",
        "name": "Tamoxifen",
        "otherNames": [
          "Tamoxifen 20mg"
        ],
        "type": "DRUG"
      }
    },
    {
      "op": "add",
      "path": "/protocolSection/armsInterventionsModule/interventions/2",
      "value": {
        "armGroupLabels": [
          "Palbociclib 100mg and, fulvestrant or tamoxifen",
          "Palbociclib 125mg and, fulvestrant or tamoxifen"
        ],
        "description": "Given by intramuscular (IM) injection.",
        "name": "Fulvestrant",
        "otherNames": [
          "Faslodex"
        ],
        "type": "DRUG"
      }
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
      "value": "Percentage of Participants With Grade 3 or 4 Neutropenia"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/measure",
      "value": "Proportion of Participants With Demonstrated Clinical Benefit"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
      "value": "Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) at 24 weeks.\nOnly those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response."
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
      "value": "24 weeks"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/measure",
      "value": "Proportion of Participants With an Objective Response"
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
      "value": "Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) at 24 weeks.\nOnly those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response."
    },
    {
      "op": "replace",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
      "value": "24 weeks"
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/3",
      "value": {
        "description": "Median change in percent positive cells of Ki-67 from baseline will be reported with IQR",
        "measure": "Median Change in Percent Positive Cells From Baseline of Ki-67",
        "timeFrame": "Up to 24 months"
      }
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/4",
      "value": {
        "description": "Median change in percent positive cells of Total-Rb from baseline will be reported with interquartile range (IQR)",
        "measure": "Median Change in Percent Positive Cells From Baseline of Total-Rb",
        "timeFrame": "Up to 24 months"
      }
    },
    {
      "op": "add",
      "path": "/protocolSection/outcomesModule/secondaryOutcomes/5",
      "value": {
        "description": "Median change in percent positive cells of pS780-Rb from baseline will be reported with IQR",
        "measure": "Median Change in Percent Positive Cells From Baseline of pS780-Rb",
        "timeFrame": "Up to 24 months"
      }
    },
    {
      "op": "remove",
      "path": "/annotationSection"
    },
    {
      "op": "replace",
      "path": "/hasResults",
      "value": true
    },
    {
      "op": "add",
      "path": "/resultsSection",
      "value": {
        "adverseEventsModule": {
          "eventGroups": [
            {
              "deathsNumAffected": 3,
              "deathsNumAtRisk": 36,
              "description": "Palbociclib dose 100mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
              "id": "EG000",
              "otherNumAffected": 7,
              "otherNumAtRisk": 36,
              "seriousNumAffected": 5,
              "seriousNumAtRisk": 36,
              "title": "Palbociclib 100mg"
            },
            {
              "deathsNumAffected": 1,
              "deathsNumAtRisk": 34,
              "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
              "id": "EG001",
              "otherNumAffected": 9,
              "otherNumAtRisk": 34,
              "seriousNumAffected": 2,
              "seriousNumAtRisk": 34,
              "title": "Palbociclib 125mg"
            }
          ],
          "frequencyThreshold": "5",
          "otherEvents": [
            {
              "assessmentType": "SYSTEMATIC_ASSESSMENT",
              "organSystem": "Investigations",
              "sourceVocabulary": "CTCAE (4.0)",
              "stats": [
                {
                  "groupId": "EG000",
                  "numAffected": 5,
                  "numAtRisk": 36,
                  "numEvents": 12
                },
                {
                  "groupId": "EG001",
                  "numAffected": 9,
                  "numAtRisk": 34,
                  "numEvents": 19
                }
              ],
              "term": "Neutrophil count decreased"
            },
            {
              "assessmentType": "SYSTEMATIC_ASSESSMENT",
              "organSystem": "Vascular disorders",
              "sourceVocabulary": "CTCAE (4.0)",
              "stats": [
                {
                  "groupId": "EG000",
                  "numAffected": 2,
                  "numAtRisk": 36,
                  "numEvents": 2
                },
                {
                  "groupId": "EG001",
                  "numAffected": 0,
                  "numAtRisk": 34,
                  "numEvents": 0
                }
              ],
              "term": "Hypertension"
            }
          ],
          "seriousEvents": [
            {
              "assessmentType": "SYSTEMATIC_ASSESSMENT",
              "organSystem": "Gastrointestinal disorders",
              "sourceVocabulary": "CTCAE (4.0)",
              "stats": [
                {
                  "groupId": "EG000",
                  "numAffected": 1,
                  "numAtRisk": 36,
                  "numEvents": 1
                },
                {
                  "groupId": "EG001",
                  "numAffected": 1,
                  "numAtRisk": 34,
                  "numEvents": 1
                }
              ],
              "term": "Gastrointestinal disorders - Other"
            },
            {
              "assessmentType": "SYSTEMATIC_ASSESSMENT",
              "organSystem": "Infections and infestations",
              "sourceVocabulary": "CTCAE (4.0)",
              "stats": [
                {
                  "groupId": "EG000",
                  "numAffected": 1,
                  "numAtRisk": 36,
                  "numEvents": 1
                },
                {
                  "groupId": "EG001",
                  "numAffected": 0,
                  "numAtRisk": 34,
                  "numEvents": 0
                }
              ],
              "term": "Infections and infestations - Other"
            },
            {
              "assessmentType": "SYSTEMATIC_ASSESSMENT",
              "organSystem": "Metabolism and nutrition disorders",
              "sourceVocabulary": "CTCAE (4.0)",
              "stats": [
                {
                  "groupId": "EG000",
                  "numAffected": 0,
                  "numAtRisk": 36,
                  "numEvents": 0
                },
                {
                  "groupId": "EG001",
                  "numAffected": 1,
                  "numAtRisk": 34,
                  "numEvents": 1
                }
              ],
              "term": "Dehydration"
            },
            {
              "assessmentType": "SYSTEMATIC_ASSESSMENT",
              "organSystem": "Respiratory, thoracic and mediastinal disorders",
              "sourceVocabulary": "CTCAE (4.0)",
              "stats": [
                {
                  "groupId": "EG000",
                  "numAffected": 2,
                  "numAtRisk": 36,
                  "numEvents": 2
                },
                {
                  "groupId": "EG001",
                  "numAffected": 0,
                  "numAtRisk": 34,
                  "numEvents": 0
                }
              ],
              "term": "Pleural effusion"
            },
            {
              "assessmentType": "SYSTEMATIC_ASSESSMENT",
              "organSystem": "Respiratory, thoracic and mediastinal disorders",
              "sourceVocabulary": "CTCAE (4.0)",
              "stats": [
                {
                  "groupId": "EG000",
                  "numAffected": 1,
                  "numAtRisk": 36,
                  "numEvents": 1
                },
                {
                  "groupId": "EG001",
                  "numAffected": 0,
                  "numAtRisk": 34,
                  "numEvents": 0
                }
              ],
              "term": "Respiratory, thoracic and mediastinal disorders - Other"
            }
          ],
          "timeFrame": "Up to 24 months"
        },
        "baselineCharacteristicsModule": {
          "denoms": [
            {
              "counts": [
                {
                  "groupId": "BG000",
                  "value": "36"
                },
                {
                  "groupId": "BG001",
                  "value": "34"
                },
                {
                  "groupId": "BG002",
                  "value": "70"
                }
              ],
              "units": "Participants"
            }
          ],
          "groups": [
            {
              "description": "Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
              "id": "BG000",
              "title": "Palbociclib 100mg"
            },
            {
              "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
              "id": "BG001",
              "title": "Palbociclib 125mg"
            },
            {
              "description": "Total of all reporting groups",
              "id": "BG002",
              "title": "Total"
            }
          ],
          "measures": [
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "1"
                        },
                        {
                          "groupId": "BG001",
                          "value": "0"
                        },
                        {
                          "groupId": "BG002",
                          "value": "1"
                        }
                      ]
                    }
                  ],
                  "title": "30-39 years old"
                },
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "5"
                        },
                        {
                          "groupId": "BG001",
                          "value": "7"
                        },
                        {
                          "groupId": "BG002",
                          "value": "12"
                        }
                      ]
                    }
                  ],
                  "title": "40-49 years old"
                },
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "11"
                        },
                        {
                          "groupId": "BG001",
                          "value": "15"
                        },
                        {
                          "groupId": "BG002",
                          "value": "26"
                        }
                      ]
                    }
                  ],
                  "title": "50-59 years old"
                },
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "12"
                        },
                        {
                          "groupId": "BG001",
                          "value": "5"
                        },
                        {
                          "groupId": "BG002",
                          "value": "17"
                        }
                      ]
                    }
                  ],
                  "title": "60-69 years old"
                },
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "5"
                        },
                        {
                          "groupId": "BG001",
                          "value": "6"
                        },
                        {
                          "groupId": "BG002",
                          "value": "11"
                        }
                      ]
                    }
                  ],
                  "title": "70-79 years old"
                },
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "2"
                        },
                        {
                          "groupId": "BG001",
                          "value": "1"
                        },
                        {
                          "groupId": "BG002",
                          "value": "3"
                        }
                      ]
                    }
                  ],
                  "title": "80-89 years old"
                }
              ],
              "paramType": "COUNT_OF_PARTICIPANTS",
              "title": "Age, Customized",
              "unitOfMeasure": "Participants"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "36"
                        },
                        {
                          "groupId": "BG001",
                          "value": "33"
                        },
                        {
                          "groupId": "BG002",
                          "value": "69"
                        }
                      ],
                      "title": "Female"
                    },
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "0"
                        },
                        {
                          "groupId": "BG001",
                          "value": "1"
                        },
                        {
                          "groupId": "BG002",
                          "value": "1"
                        }
                      ],
                      "title": "Male"
                    }
                  ]
                }
              ],
              "paramType": "COUNT_OF_PARTICIPANTS",
              "title": "Sex: Female, Male",
              "unitOfMeasure": "Participants"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "1"
                        },
                        {
                          "groupId": "BG001",
                          "value": "0"
                        },
                        {
                          "groupId": "BG002",
                          "value": "1"
                        }
                      ],
                      "title": "Hispanic or Latino"
                    },
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "33"
                        },
                        {
                          "groupId": "BG001",
                          "value": "33"
                        },
                        {
                          "groupId": "BG002",
                          "value": "66"
                        }
                      ],
                      "title": "Not Hispanic or Latino"
                    },
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "2"
                        },
                        {
                          "groupId": "BG001",
                          "value": "1"
                        },
                        {
                          "groupId": "BG002",
                          "value": "3"
                        }
                      ],
                      "title": "Unknown or Not Reported"
                    }
                  ]
                }
              ],
              "paramType": "COUNT_OF_PARTICIPANTS",
              "title": "Ethnicity (NIH&#x2F;OMB)",
              "unitOfMeasure": "Participants"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "0"
                        },
                        {
                          "groupId": "BG001",
                          "value": "0"
                        },
                        {
                          "groupId": "BG002",
                          "value": "0"
                        }
                      ],
                      "title": "American Indian or Alaska Native"
                    },
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "1"
                        },
                        {
                          "groupId": "BG001",
                          "value": "2"
                        },
                        {
                          "groupId": "BG002",
                          "value": "3"
                        }
                      ],
                      "title": "Asian"
                    },
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "0"
                        },
                        {
                          "groupId": "BG001",
                          "value": "1"
                        },
                        {
                          "groupId": "BG002",
                          "value": "1"
                        }
                      ],
                      "title": "Native Hawaiian or Other Pacific Islander"
                    },
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "2"
                        },
                        {
                          "groupId": "BG001",
                          "value": "1"
                        },
                        {
                          "groupId": "BG002",
                          "value": "3"
                        }
                      ],
                      "title": "Black or African American"
                    },
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "28"
                        },
                        {
                          "groupId": "BG001",
                          "value": "26"
                        },
                        {
                          "groupId": "BG002",
                          "value": "54"
                        }
                      ],
                      "title": "White"
                    },
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "0"
                        },
                        {
                          "groupId": "BG001",
                          "value": "0"
                        },
                        {
                          "groupId": "BG002",
                          "value": "0"
                        }
                      ],
                      "title": "More than one race"
                    },
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "5"
                        },
                        {
                          "groupId": "BG001",
                          "value": "4"
                        },
                        {
                          "groupId": "BG002",
                          "value": "9"
                        }
                      ],
                      "title": "Unknown or Not Reported"
                    }
                  ]
                }
              ],
              "paramType": "COUNT_OF_PARTICIPANTS",
              "title": "Race (NIH&#x2F;OMB)",
              "unitOfMeasure": "Participants"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "BG000",
                          "value": "36"
                        },
                        {
                          "groupId": "BG001",
                          "value": "34"
                        },
                        {
                          "groupId": "BG002",
                          "value": "70"
                        }
                      ]
                    }
                  ],
                  "title": "United States"
                }
              ],
              "paramType": "NUMBER",
              "title": "Region of Enrollment",
              "unitOfMeasure": "participants"
            }
          ]
        },
        "moreInfoModule": {
          "certainAgreement": {
            "piSponsorEmployee": true
          },
          "pointOfContact": {
            "email": "Hope.Rugo@ucsf.edu",
            "organization": "University of California, San Francisco",
            "phone": "(415) 353-7618",
            "title": "Dr. Hope Rugo, MD"
          }
        },
        "outcomeMeasuresModule": {
          "outcomeMeasures": [
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "OG000",
                          "value": "19.4"
                        },
                        {
                          "groupId": "OG001",
                          "value": "20.5"
                        }
                      ]
                    }
                  ]
                }
              ],
              "denoms": [
                {
                  "counts": [
                    {
                      "groupId": "OG000",
                      "value": "36"
                    },
                    {
                      "groupId": "OG001",
                      "value": "34"
                    }
                  ],
                  "units": "Participants"
                }
              ],
              "description": "Grade 3&#x2F;4 neutropenia as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03 in patients with prior exposure to 1-3 lines of chemotherapy for metastatic breast cancer",
              "groups": [
                {
                  "description": "Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG000",
                  "title": "Palbociclib 100mg"
                },
                {
                  "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG001",
                  "title": "Palbociclib 125mg"
                }
              ],
              "paramType": "NUMBER",
              "reportingStatus": "POSTED",
              "timeFrame": "Up to 24 months",
              "title": "Percentage of Participants With Grade 3 or 4 Neutropenia",
              "type": "PRIMARY",
              "unitOfMeasure": "percentage of participants"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "OG000",
                          "lowerLimit": "2.33",
                          "upperLimit": "12.2",
                          "value": "6.53"
                        },
                        {
                          "groupId": "OG001",
                          "lowerLimit": "3.56",
                          "upperLimit": "19.7",
                          "value": "9.4"
                        }
                      ]
                    }
                  ]
                }
              ],
              "denoms": [
                {
                  "counts": [
                    {
                      "groupId": "OG000",
                      "value": "36"
                    },
                    {
                      "groupId": "OG001",
                      "value": "34"
                    }
                  ],
                  "units": "Participants"
                }
              ],
              "description": "PFS defined as the interval from study entry to the first documented evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter (SLD) of target lesions, taking as reference the smallest sum SLD recorded since the treatment started and minimum 5 mm increase over the nadir, or the appearance of one or more new lesions.\nPatients who remain progression-free at the time of analysis will be censored at their last date of follow-up.",
              "dispersionType": "95% Confidence Interval",
              "groups": [
                {
                  "description": "Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG000",
                  "title": "Palbociclib 100mg"
                },
                {
                  "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG001",
                  "title": "Palbociclib 125mg"
                }
              ],
              "paramType": "MEDIAN",
              "reportingStatus": "POSTED",
              "timeFrame": "Up to 24 months",
              "title": "Progression-free Survival (PFS)",
              "type": "SECONDARY",
              "unitOfMeasure": "months"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "OG000",
                          "value": "0.67"
                        },
                        {
                          "groupId": "OG001",
                          "value": "0.75"
                        }
                      ]
                    }
                  ]
                }
              ],
              "denoms": [
                {
                  "counts": [
                    {
                      "groupId": "OG000",
                      "value": "36"
                    },
                    {
                      "groupId": "OG001",
                      "value": "32"
                    }
                  ],
                  "units": "Participants"
                }
              ],
              "description": "Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) at 24 weeks.\nOnly those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.",
              "groups": [
                {
                  "description": "Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG000",
                  "title": "Palbociclib 100mg"
                },
                {
                  "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG001",
                  "title": "Palbociclib 125mg"
                }
              ],
              "paramType": "NUMBER",
              "populationDescription": "Two participants in the 125mg group did not have an evaluable disease assessment 24 weeks",
              "reportingStatus": "POSTED",
              "timeFrame": "24 weeks",
              "title": "Proportion of Participants With Demonstrated Clinical Benefit",
              "type": "SECONDARY",
              "unitOfMeasure": "proportion of participants"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "OG000",
                          "value": "0.1111"
                        },
                        {
                          "groupId": "OG001",
                          "value": "0.0625"
                        }
                      ]
                    }
                  ]
                }
              ],
              "denoms": [
                {
                  "counts": [
                    {
                      "groupId": "OG000",
                      "value": "36"
                    },
                    {
                      "groupId": "OG001",
                      "value": "32"
                    }
                  ],
                  "units": "Participants"
                }
              ],
              "description": "Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) at 24 weeks.\nOnly those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.",
              "groups": [
                {
                  "description": "Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG000",
                  "title": "Palbociclib 100mg"
                },
                {
                  "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG001",
                  "title": "Palbociclib 125mg"
                }
              ],
              "paramType": "NUMBER",
              "populationDescription": "Two participants in the 125mg group did not have an evaluable disease assessment 24 weeks",
              "reportingStatus": "POSTED",
              "timeFrame": "24 weeks",
              "title": "Proportion of Participants With an Objective Response",
              "type": "SECONDARY",
              "unitOfMeasure": "proportion of participants"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "OG000",
                          "lowerLimit": "-22",
                          "upperLimit": "0",
                          "value": "-8"
                        },
                        {
                          "groupId": "OG001",
                          "lowerLimit": "-19",
                          "upperLimit": "-1",
                          "value": "-6"
                        }
                      ]
                    }
                  ]
                }
              ],
              "denoms": [
                {
                  "counts": [
                    {
                      "groupId": "OG000",
                      "value": "36"
                    },
                    {
                      "groupId": "OG001",
                      "value": "34"
                    }
                  ],
                  "units": "Participants"
                }
              ],
              "description": "Median change in percent positive cells of Ki-67 from baseline will be reported with IQR",
              "dispersionType": "Inter-Quartile Range",
              "groups": [
                {
                  "description": "Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG000",
                  "title": "Palbociclib 100mg"
                },
                {
                  "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG001",
                  "title": "Palbociclib 125mg"
                }
              ],
              "paramType": "MEDIAN",
              "reportingStatus": "POSTED",
              "timeFrame": "Up to 24 months",
              "title": "Median Change in Percent Positive Cells From Baseline of Ki-67",
              "type": "SECONDARY",
              "unitOfMeasure": "change in percent positive cells"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "OG000",
                          "lowerLimit": "-25",
                          "upperLimit": "30",
                          "value": "4"
                        },
                        {
                          "groupId": "OG001",
                          "lowerLimit": "-15",
                          "upperLimit": "29",
                          "value": "5"
                        }
                      ]
                    }
                  ]
                }
              ],
              "denoms": [
                {
                  "counts": [
                    {
                      "groupId": "OG000",
                      "value": "36"
                    },
                    {
                      "groupId": "OG001",
                      "value": "34"
                    }
                  ],
                  "units": "Participants"
                }
              ],
              "description": "Median change in percent positive cells of Total-Rb from baseline will be reported with interquartile range (IQR)",
              "dispersionType": "Inter-Quartile Range",
              "groups": [
                {
                  "description": "Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG000",
                  "title": "Palbociclib 100mg"
                },
                {
                  "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG001",
                  "title": "Palbociclib 125mg"
                }
              ],
              "paramType": "MEDIAN",
              "reportingStatus": "POSTED",
              "timeFrame": "Up to 24 months",
              "title": "Median Change in Percent Positive Cells From Baseline of Total-Rb",
              "type": "SECONDARY",
              "unitOfMeasure": "change in percent positive cells"
            },
            {
              "classes": [
                {
                  "categories": [
                    {
                      "measurements": [
                        {
                          "groupId": "OG000",
                          "lowerLimit": "-32",
                          "upperLimit": "4",
                          "value": "-3"
                        },
                        {
                          "groupId": "OG001",
                          "lowerLimit": "-14",
                          "upperLimit": "12",
                          "value": "-6"
                        }
                      ]
                    }
                  ]
                }
              ],
              "denoms": [
                {
                  "counts": [
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                      "groupId": "OG000",
                      "value": "36"
                    },
                    {
                      "groupId": "OG001",
                      "value": "34"
                    }
                  ],
                  "units": "Participants"
                }
              ],
              "description": "Median change in percent positive cells of pS780-Rb from baseline will be reported with IQR",
              "dispersionType": "Inter-Quartile Range",
              "groups": [
                {
                  "description": "Treatment arm palbociclib dose 100mg + fulvestrant or tamoxifen",
                  "id": "OG000",
                  "title": "Palbociclib 100mg"
                },
                {
                  "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
                  "id": "OG001",
                  "title": "Palbociclib 125mg"
                }
              ],
              "paramType": "MEDIAN",
              "reportingStatus": "POSTED",
              "timeFrame": "Up to 24 months",
              "title": "Median Change in Percent Positive Cells From Baseline of pS780-Rb",
              "type": "SECONDARY",
              "unitOfMeasure": "change in percent positive cells"
            }
          ]
        },
        "participantFlowModule": {
          "groups": [
            {
              "description": "Palbociclib dose 100mg, and either fulvestrant (500 mg intramuscular injection (IM) on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
              "id": "FG000",
              "title": "Palbociclib 100mg"
            },
            {
              "description": "Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)",
              "id": "FG001",
              "title": "Palbociclib 125mg"
            }
          ],
          "periods": [
            {
              "milestones": [
                {
                  "achievements": [
                    {
                      "groupId": "FG000",
                      "numSubjects": "36"
                    },
                    {
                      "groupId": "FG001",
                      "numSubjects": "34"
                    }
                  ],
                  "type": "STARTED"
                },
                {
                  "achievements": [
                    {
                      "groupId": "FG000",
                      "numSubjects": "36"
                    },
                    {
                      "groupId": "FG001",
                      "numSubjects": "34"
                    }
                  ],
                  "type": "COMPLETED"
                },
                {
                  "achievements": [
                    {
                      "groupId": "FG000",
                      "numSubjects": "0"
                    },
                    {
                      "groupId": "FG001",
                      "numSubjects": "0"
                    }
                  ],
                  "type": "NOT COMPLETED"
                }
              ],
              "title": "Overall Study"
            }
          ]
        }
      }
    },
    {
      "op": "add",
      "path": "/documentSection",
      "value": {
        "largeDocumentModule": {
          "largeDocs": [
            {
              "date": "2017-03-01",
              "filename": "Prot_SAP_000.pdf",
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              "hasProtocol": true,
              "hasSap": true,
              "label": "Study Protocol and Statistical Analysis Plan",
              "size": 12917068,
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              "uploadDate": "2021-11-22T21:31"
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  "provenance": {
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    "materiality_event_hash": "c5de097b2b917f30c1fc0a5422faa591a482dcda730b587f034ddb3a88230584",
    "patch_hash": "437a41d166c3290558adc37f01e3733284cc4d6931fbdf8059b2a3b9a70a02b8",
    "patch_raw_hash": "e978abf3ba96a5240a3359f327dd63a34418690bb9d0e971aacc1d0f835e6d97",
    "patch_source": "ctgov_internal_history",
    "patch_source_url": "https://clinicaltrials.gov/api/int/studies/NCT02384239/history/8?patchToVersion=9",
    "to_snapshot_hash": null
  },
  "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/NCT02384239",
    "nct_id": "NCT02384239"
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  "versions": {
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    "submitted_date": "2022-02-16",
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