Evidence Record
evt_NCT03584009_v22_v23_c5cb4c8764cb
NCT03584009 · A Phase II Study Comparing The Efficacy Of Venetoclax + Fulvestrant Vs. Fulvestrant In Women With Estrogen Receptor-Positive, Her2-Negative Locally Advanced Or Metastatic Breast Cancer Who Experienced Disease Recurrence Or Progression During Or After CDK4/6 Inhibitor Therapy
Superseded Evidence Record
This page preserves the immutable v0.1.2 record. Its current successor is evt_NCT03584009_v22_v23_5f7befd0ee38.
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: High Category
Arm Intervention Change
Versions
v22 to v23
Timing
Post Recruitment
Claims Supported
- TrialDiff compared ClinicalTrials.gov record version 22 to version 23 for NCT03584009.
- The JSON Patch for this comparison has hash 1841dd9bd64477dede1bc17cb87ff3dfc6a1eb26339279cd35d368f6854ca820.
- The active deterministic rule set hash was 318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86.
- 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, secondary_outcome_removed_after_primary_completion.
- A registry field under an arm or intervention module changed between ClinicalTrials.gov versions 22 and 23.
- 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/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/statusModule/resultsFirstSubmitDate, /protocolSection/armsInterventionsModule/armGroups/0/description, /protocolSection/armsInterventionsModule/armGroups/1/description, /protocolSection/armsInterventionsModule/interventions/0/description, /protocolSection/armsInterventionsModule/interventions/1/description, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/0/description, /protocolSection/outcomesModule/primaryOutcomes/0/reviewUnit, /protocolSection/outcomesModule/secondaryOutcomes/0/description, /protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/1/description, /protocolSection/outcomesModule/secondaryOutcomes/1/reviewUnit, /protocolSection/outcomesModule/secondaryOutcomes/2/description, /protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/3/description, /protocolSection/outcomesModule/secondaryOutcomes/4/measure, /protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/4/description, /protocolSection/outcomesModule/secondaryOutcomes/5/measure, /protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/5/description, /protocolSection/outcomesModule/secondaryOutcomes/6/measure, /protocolSection/outcomesModule/secondaryOutcomes/6/description, /protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/7, /protocolSection/outcomesModule/secondaryOutcomes/7, /hasResults, /resultsSection, /annotationSection, /documentSection.
- An outcome path changed between versions 22 and 23 in a patch that also carried a hasResults or resultsSection co-occurrence signal.
- The JSON Patch removed a whole secondary outcome item after primary completion between versions 22 and 23; when a TO-version outcome list is available, reindex-only removals are excluded.
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_NCT03584009_v22_v23_c5cb4c8764cb. ClinicalTrials.gov NCT03584009, versions 22-23. Evidence version 1.
Event Classes
outcome_edit_cooccurs_with_results_postingsecondary_outcome_removed_after_primary_completion Changed Paths
/protocolSection/statusModule/statusVerifiedDate
/protocolSection/statusModule/lastUpdateSubmitDate
/protocolSection/statusModule/lastUpdatePostDateStruct/date
/protocolSection/statusModule/resultsFirstSubmitDate
/protocolSection/armsInterventionsModule/armGroups/0/description
/protocolSection/armsInterventionsModule/armGroups/1/description
/protocolSection/armsInterventionsModule/interventions/0/description
/protocolSection/armsInterventionsModule/interventions/1/description
/protocolSection/outcomesModule/primaryOutcomes/0/measure
/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame
/protocolSection/outcomesModule/primaryOutcomes/0/description
/protocolSection/outcomesModule/primaryOutcomes/0/reviewUnit
/protocolSection/outcomesModule/secondaryOutcomes/0/description
/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/1/description
/protocolSection/outcomesModule/secondaryOutcomes/1/reviewUnit
/protocolSection/outcomesModule/secondaryOutcomes/2/description
/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/3/description
/protocolSection/outcomesModule/secondaryOutcomes/4/measure
/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/4/description
/protocolSection/outcomesModule/secondaryOutcomes/5/measure
/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/5/description
/protocolSection/outcomesModule/secondaryOutcomes/6/measure
/protocolSection/outcomesModule/secondaryOutcomes/6/description
/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame
/protocolSection/outcomesModule/secondaryOutcomes/7
/protocolSection/outcomesModule/secondaryOutcomes/7
/hasResults
/resultsSection
/annotationSection
/documentSection
View the field-level diff for before/after values on each changed path.
Deterministic Rules
arms_or_interventions_change Provenance
- Package generation
v0.1.2- Succeeded by
- evt_NCT03584009_v22_v23_5f7befd0ee38
- Patch hash
1841dd9bd64477dede1bc17cb87ff3dfc6a1eb26339279cd35d368f6854ca820- Canonical hash
f695917c86cc4619f1740fbf62e2029ad3f966588585996916907e04bf8348ab- Rule set hash
318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86- From snapshot
8b528fc806f8964cf3d27ab3e5e2e8b2edae9eb85843decc0b01e7f397eebb16- To snapshot
d90013009571884d9f307aed5af127502c4d2d0fc7770953e56dc5be29688f0e- 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/statusVerifiedDate",
"/protocolSection/statusModule/lastUpdateSubmitDate",
"/protocolSection/statusModule/lastUpdatePostDateStruct/date",
"/protocolSection/statusModule/resultsFirstSubmitDate",
"/protocolSection/armsInterventionsModule/armGroups/0/description",
"/protocolSection/armsInterventionsModule/armGroups/1/description",
"/protocolSection/armsInterventionsModule/interventions/0/description",
"/protocolSection/armsInterventionsModule/interventions/1/description",
"/protocolSection/outcomesModule/primaryOutcomes/0/measure",
"/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/primaryOutcomes/0/description",
"/protocolSection/outcomesModule/primaryOutcomes/0/reviewUnit",
"/protocolSection/outcomesModule/secondaryOutcomes/0/description",
"/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/1/description",
"/protocolSection/outcomesModule/secondaryOutcomes/1/reviewUnit",
"/protocolSection/outcomesModule/secondaryOutcomes/2/description",
"/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/3/description",
"/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/4/description",
"/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/5/description",
"/protocolSection/outcomesModule/secondaryOutcomes/6/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/6/description",
"/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/7",
"/protocolSection/outcomesModule/secondaryOutcomes/7",
"/hasResults",
"/resultsSection",
"/annotationSection",
"/documentSection"
],
"citation_text": "TrialDiff Evidence Record evt_NCT03584009_v22_v23_c5cb4c8764cb. ClinicalTrials.gov NCT03584009, versions 22-23. 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 22 to version 23 for NCT03584009.",
"The JSON Patch for this comparison has hash 1841dd9bd64477dede1bc17cb87ff3dfc6a1eb26339279cd35d368f6854ca820.",
"The active deterministic rule set hash was 318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86.",
"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, secondary_outcome_removed_after_primary_completion.",
"A registry field under an arm or intervention module changed between ClinicalTrials.gov versions 22 and 23.",
"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/lastUpdateSubmitDate, /protocolSection/statusModule/lastUpdatePostDateStruct/date, /protocolSection/statusModule/resultsFirstSubmitDate, /protocolSection/armsInterventionsModule/armGroups/0/description, /protocolSection/armsInterventionsModule/armGroups/1/description, /protocolSection/armsInterventionsModule/interventions/0/description, /protocolSection/armsInterventionsModule/interventions/1/description, /protocolSection/outcomesModule/primaryOutcomes/0/measure, /protocolSection/outcomesModule/primaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/primaryOutcomes/0/description, /protocolSection/outcomesModule/primaryOutcomes/0/reviewUnit, /protocolSection/outcomesModule/secondaryOutcomes/0/description, /protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/1/description, /protocolSection/outcomesModule/secondaryOutcomes/1/reviewUnit, /protocolSection/outcomesModule/secondaryOutcomes/2/description, /protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/3/description, /protocolSection/outcomesModule/secondaryOutcomes/4/measure, /protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/4/description, /protocolSection/outcomesModule/secondaryOutcomes/5/measure, /protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/5/description, /protocolSection/outcomesModule/secondaryOutcomes/6/measure, /protocolSection/outcomesModule/secondaryOutcomes/6/description, /protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame, /protocolSection/outcomesModule/secondaryOutcomes/7, /protocolSection/outcomesModule/secondaryOutcomes/7, /hasResults, /resultsSection, /annotationSection, /documentSection.",
"An outcome path changed between versions 22 and 23 in a patch that also carried a hasResults or resultsSection co-occurrence signal.",
"The JSON Patch removed a whole secondary outcome item after primary completion between versions 22 and 23; when a TO-version outcome list is available, reindex-only removals are excluded."
],
"classification": {
"calibration_status": "uncalibrated",
"categories": [
"arm_intervention_change",
"results_reconciliation"
],
"category": "arm_intervention_change",
"deterministic_rules": [
"arms_or_interventions_change"
],
"event_class_rule_set_hash": "07957f8b90549d4f42387f51b471ecde9901b6db63bbc27b84c73631603407c0",
"event_classes": [
"outcome_edit_cooccurs_with_results_posting",
"secondary_outcome_removed_after_primary_completion"
],
"rule_set_hash": "318445b9ad266f51fd10ef378645c753ba7a098e3e4395c3c457750dc5f88d86",
"severity": "high",
"severity_pre_timing": "high",
"timing_context": "post_recruitment",
"triage_label": "high",
"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/reviewUnit",
"/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/0/description",
"/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/1/description",
"/protocolSection/outcomesModule/secondaryOutcomes/1/reviewUnit",
"/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/2/description",
"/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/3/description",
"/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/4/description",
"/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/5/description",
"/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/6/description",
"/protocolSection/outcomesModule/secondaryOutcomes/6/measure",
"/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
"/protocolSection/outcomesModule/secondaryOutcomes/7"
],
"severity": "low",
"signal": "results_reconciliation_outcome_suppression"
}
]
},
"event_id": "evt_NCT03584009_v22_v23_c5cb4c8764cb",
"evidence_version": 1,
"patch": [
{
"op": "replace",
"path": "/protocolSection/statusModule/statusVerifiedDate",
"value": "2021-07"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdateSubmitDate",
"value": "2021-07-20"
},
{
"op": "replace",
"path": "/protocolSection/statusModule/lastUpdatePostDateStruct/date",
"value": "2021-08-12"
},
{
"op": "add",
"path": "/protocolSection/statusModule/resultsFirstSubmitDate",
"value": "2021-07-20"
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/0/description",
"value": "Participants were administered Venetoclax 800mg orally once daily (QD) and Fulvestrant 500mg intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days)."
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/armGroups/1/description",
"value": "Participants were administered Fulvestrant 500mg only intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days)."
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/interventions/0/description",
"value": "Venetoclax was administered orally, 800-mg tablet beginning on Cycle 1 Day 1 until the 9th October 2020."
},
{
"op": "replace",
"path": "/protocolSection/armsInterventionsModule/interventions/1/description",
"value": "Fulvestrant was administered orally, 500 mg administered as two 250-mg intramuscular (IM) injections on Cycle 1 Days 1 and 15 and on Day 1 of each subsequent 28-day cycle"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/measure",
"value": "Clinical Benefit Defined as Complete Response (CR), Partial Response (PR) or Stable Disease (SD) Lasting >= 24 Weeks, as Determined by the Investigator According to RECIST v1.1"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/timeFrame",
"value": "Randomization through till 6 months after the last participant is enrolled into the study."
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/description",
"value": "Clinical Benefit was defined as Complete Response, Partial Response, or Stable Disease lasting more than equal to 24 weeks from randomization in participants with measurable disease at baseline, as determined by the investigator according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1.\nPer RECIST v1.1 for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the diameters of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Disease Progression (PD), taking as reference the smallest sum on study."
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/primaryOutcomes/0/reviewUnit",
"value": {
"resetReasons": [
"There does not appear to be sufficient information to understand the Time Frame."
]
}
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/0/description",
"value": "PFS was defined as the time from randomization to the first occurrence of disease progression (as determined by the investigator according to RECIST v1.1) or death from any cause, whichever occurs first."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/0/timeFrame",
"value": "Randomization through till 6 months after the last participant is enrolled into the study."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/1/timeFrame",
"value": "Randomization through till 6 months after the last participant is enrolled into the study."
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/1/description",
"value": "OR was defined as Complete Response (CR) or Partial response (PR), in participants with measurable disease at baseline as determined by the investigator according to RECIST v1.1."
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/1/reviewUnit",
"value": {
"resetReasons": [
"There does not appear to be sufficient information to understand the Time Frame."
]
}
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/2/description",
"value": "DOR was defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression (as determined by the investigator according to RECIST v1.1) or death from any cause, whichever occurs first."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/2/timeFrame",
"value": "Time from first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, until 6 months after the last participant is enrolled into the study."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/timeFrame",
"value": "Randomization to death from any cause, through till the end of the study (2 years after the last participant is enrolled)."
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/3/description",
"value": "Overall Survival (OS) is defined as the time from randomization to death due to any cause.\nData collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/measure",
"value": "Percentage of Participants With Adverse Events (AEs)"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/timeFrame",
"value": "Baseline up until 28 days after the last dose of study drug (venetoclax or fulvestrant, whichever is later)."
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/4/description",
"value": "An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment.\nAn Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.\nPreexisting conditions which worsen during a study are also considered as Adverse Events.\nData collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/measure",
"value": "Plasma Concentrations of Venetoclax at Specified Timepoints"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/timeFrame",
"value": "At pre-defined intervals from Cycle 1, Day 1, through till the end of treatment (2 years after the last participant is enrolled)."
},
{
"op": "add",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/5/description",
"value": "The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received.\nDescriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.\nData collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/6/measure",
"value": "Plasma Concentrations of Fulvestrant at Specified Timepoints"
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/6/description",
"value": "The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received.\nDescriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.\nData collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date."
},
{
"op": "replace",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/6/timeFrame",
"value": "At pre-defined intervals from Cycle 1, Day 1, through till the end of treatment (2 years after the last participant is enrolled)."
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/7"
},
{
"op": "remove",
"path": "/protocolSection/outcomesModule/secondaryOutcomes/7"
},
{
"op": "replace",
"path": "/hasResults",
"value": true
},
{
"op": "add",
"path": "/resultsSection",
"value": {
"adverseEventsModule": {
"description": "The 1 additional death in the Venetoclax + Fulvestrant arm compared to in the Participant Flow section, relates to a participant who had withdrawn consent from the study and later died.\nTheir death was reported in public records (reported as a post study reporting death).",
"eventGroups": [
{
"deathsNumAffected": 19,
"deathsNumAtRisk": 50,
"description": "Participants were administered Venetoclax 800mg orally once daily (QD) and Fulvestrant 500mg intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "EG000",
"otherNumAffected": 45,
"otherNumAtRisk": 50,
"seriousNumAffected": 4,
"seriousNumAtRisk": 50,
"title": "Venetoclax + Fulvestrant"
},
{
"deathsNumAffected": 9,
"deathsNumAtRisk": 51,
"description": "Participants were administered Fulvestrant 500mg only intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "EG001",
"otherNumAffected": 34,
"otherNumAtRisk": 51,
"seriousNumAffected": 1,
"seriousNumAtRisk": 51,
"title": "Fulvestrant"
}
],
"frequencyThreshold": "5",
"otherEvents": [
{
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"organSystem": "Blood and lymphatic system disorders",
"sourceVocabulary": "MedDRA 23.0",
"stats": [
{
"groupId": "EG000",
"numAffected": 2,
"numAtRisk": 50,
"numEvents": 2
},
{
"groupId": "EG001",
"numAffected": 3,
"numAtRisk": 51,
"numEvents": 3
}
],
"term": "Anaemia"
},
{
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"organSystem": "Blood and lymphatic system disorders",
"sourceVocabulary": "MedDRA 23.0",
"stats": [
{
"groupId": "EG000",
"numAffected": 3,
"numAtRisk": 50,
"numEvents": 3
},
{
"groupId": "EG001",
"numAffected": 1,
"numAtRisk": 51,
"numEvents": 1
}
],
"term": "Leukopenia"
},
{
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"organSystem": "Blood and lymphatic system disorders",
"sourceVocabulary": "MedDRA 23.0",
"stats": [
{
"groupId": "EG000",
"numAffected": 7,
"numAtRisk": 50,
"numEvents": 7
},
{
"groupId": "EG001",
"numAffected": 0,
"numAtRisk": 51,
"numEvents": 0
}
],
"term": "Lymphopenia"
},
{
"assessmentType": "SYSTEMATIC_ASSESSMENT",
"organSystem": "Blood and lymphatic system disorders",
"sourceVocabulary": "MedDRA 23.0",
"stats": [
{
"groupId": "EG000",
"numAffected": 8,
"numAtRisk": 50,
"numEvents": 11
},
{
"groupId": "EG001",
"numAffected": 0,
"numAtRisk": 51,
"numEvents": 0
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"statisticalMethod": "Cochran-Mantel-Haenszel"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"lowerLimit": "4.44",
"upperLimit": "23.87",
"value": "11.8"
},
{
"groupId": "OG001",
"lowerLimit": "5.70",
"upperLimit": "26.26",
"value": "13.7"
}
]
}
]
}
],
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "51"
},
{
"groupId": "OG001",
"value": "51"
}
],
"units": "Participants"
}
],
"description": "Clinical Benefit was defined as Complete Response, Partial Response, or Stable Disease lasting more than equal to 24 weeks from randomization in participants with measurable disease at baseline, as determined by the investigator according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1.\nPer RECIST v1.1 for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the diameters of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Disease Progression (PD), taking as reference the smallest sum on study.",
"dispersionType": "95% Confidence Interval",
"groups": [
{
"description": "Participants were administered Venetoclax 800mg orally once daily (QD) and Fulvestrant 500mg intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "OG000",
"title": "Venetoclax + Fulvestrant"
},
{
"description": "Participants were administered Fulvestrant 500mg only intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "OG001",
"title": "Fulvestrant"
}
],
"paramType": "NUMBER",
"populationDescription": "The Baseline Measurable Disease Population represented all randomized participants with measurable disease at baseline.",
"reportingStatus": "POSTED",
"reviewUnit": {
"resetReasons": [
"There does not appear to be sufficient information to understand the Time Frame."
]
},
"timeFrame": "Randomization through till 6 months after the last participant is enrolled into the study.",
"title": "Clinical Benefit Defined as Complete Response (CR), Partial Response (PR) or Stable Disease (SD) Lasting >= 24 Weeks, as Determined by the Investigator According to RECIST v1.1",
"type": "PRIMARY",
"unitOfMeasure": "Percentage of Participants"
},
{
"analyses": [
{
"ciLowerLimit": "0.61",
"ciNumSides": "TWO_SIDED",
"ciPctValue": "95",
"ciUpperLimit": "1.45",
"groupIds": [
"OG000",
"OG001"
],
"nonInferiorityType": "SUPERIORITY",
"pValue": "0.7853",
"pValueComment": "P-value is based on Stratified Analysis (Stratified by BCL2 status (High vs Low) and Lines of Therapy (2 vs 1)).",
"paramType": "Hazard Ratio (HR)",
"paramValue": "0.94",
"statisticalMethod": "Regression, Cox"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"lowerLimit": "1.94",
"upperLimit": "3.71",
"value": "2.69"
},
{
"groupId": "OG001",
"lowerLimit": "1.84",
"upperLimit": "3.55",
"value": "1.94"
}
]
}
]
}
],
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "51"
},
{
"groupId": "OG001",
"value": "52"
}
],
"units": "Participants"
}
],
"description": "PFS was defined as the time from randomization to the first occurrence of disease progression (as determined by the investigator according to RECIST v1.1) or death from any cause, whichever occurs first.",
"dispersionType": "95% Confidence Interval",
"groups": [
{
"description": "Participants were administered Venetoclax 800mg orally once daily (QD) and Fulvestrant 500mg intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "OG000",
"title": "Venetoclax + Fulvestrant"
},
{
"description": "Participants were administered Fulvestrant 500mg only intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "OG001",
"title": "Fulvestrant"
}
],
"paramType": "MEDIAN",
"populationDescription": "The Intent-To-Treat (ITT) population was defined as all randomized participants whether or not they were assigned to the arm where the study treatment was administered.",
"reportingStatus": "POSTED",
"timeFrame": "Randomization through till 6 months after the last participant is enrolled into the study.",
"title": "Progression Free Survival (PFS)",
"type": "SECONDARY",
"unitOfMeasure": "Months"
},
{
"analyses": [
{
"ciLowerLimit": "-12.29",
"ciNumSides": "TWO_SIDED",
"ciPctValue": "95",
"ciUpperLimit": "8.37",
"groupIds": [
"OG000",
"OG001"
],
"nonInferiorityType": "SUPERIORITY",
"pValue": "0.5978",
"pValueComment": "P-value is based on Stratified Analysis (Stratified by BCL2 status (High vs Low) and Lines of Therapy (2 vs 1)).",
"paramType": "Risk Difference (RD)",
"paramValue": "-1.96",
"statisticalMethod": "Cochran-Mantel-Haenszel"
}
],
"classes": [
{
"categories": [
{
"measurements": [
{
"groupId": "OG000",
"lowerLimit": "0.48",
"upperLimit": "13.46",
"value": "3.9"
},
{
"groupId": "OG001",
"lowerLimit": "1.23",
"upperLimit": "16.24",
"value": "5.9"
}
]
}
]
}
],
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "51"
},
{
"groupId": "OG001",
"value": "51"
}
],
"units": "Participants"
}
],
"description": "OR was defined as Complete Response (CR) or Partial response (PR), in participants with measurable disease at baseline as determined by the investigator according to RECIST v1.1.",
"dispersionType": "95% Confidence Interval",
"groups": [
{
"description": "Participants were administered Venetoclax 800mg orally once daily (QD) and Fulvestrant 500mg intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "OG000",
"title": "Venetoclax + Fulvestrant"
},
{
"description": "Participants were administered Fulvestrant 500mg only intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "OG001",
"title": "Fulvestrant"
}
],
"paramType": "NUMBER",
"populationDescription": "The Baseline Measurable Disease Population represented all randomized participants with measurable disease at baseline.",
"reportingStatus": "POSTED",
"reviewUnit": {
"resetReasons": [
"There does not appear to be sufficient information to understand the Time Frame."
]
},
"timeFrame": "Randomization through till 6 months after the last participant is enrolled into the study.",
"title": "Objective Response (OR)",
"type": "SECONDARY",
"unitOfMeasure": "Percentage of Participants"
},
{
"classes": [
{
"categories": [
{
"measurements": [
{
"comment": "0 participants had a documented objective response (i.e.\nCR or PR) so Median, Lower and Upper Limit values could not be estimated.",
"groupId": "OG000",
"lowerLimit": "NA",
"upperLimit": "NA",
"value": "NA"
},
{
"comment": "Insufficient number of participants meant that Upper Limit value could not be estimated.",
"groupId": "OG001",
"lowerLimit": "1.94",
"upperLimit": "NA",
"value": "3.61"
}
]
}
]
}
],
"denoms": [
{
"counts": [
{
"groupId": "OG000",
"value": "2"
},
{
"groupId": "OG001",
"value": "3"
}
],
"units": "Participants"
}
],
"description": "DOR was defined as the time from the first occurrence of a documented objective response to the time of the first documented disease progression (as determined by the investigator according to RECIST v1.1) or death from any cause, whichever occurs first.",
"dispersionType": "95% Confidence Interval",
"groups": [
{
"description": "Participants were administered Venetoclax 800mg orally once daily (QD) and Fulvestrant 500mg intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "OG000",
"title": "Venetoclax + Fulvestrant"
},
{
"description": "Participants were administered Fulvestrant 500mg only intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "OG001",
"title": "Fulvestrant"
}
],
"measureCategoriesReviewUnit": {
"resetReasons": [
"The explanation provided is not sufficient to understand why one or more values are not available."
]
},
"paramType": "MEDIAN",
"populationDescription": "Only participants with a documented objective response were analysed for this Outcome Measure.",
"reportingStatus": "POSTED",
"timeFrame": "Time from first occurrence of a documented objective response to the time of the first documented disease progression or death from any cause, whichever occurs first, until 6 months after the last participant is enrolled into the study.",
"title": "Duration of Response (DOR)",
"type": "SECONDARY",
"unitOfMeasure": "Months"
},
{
"anticipatedPostingDate": "2022-05",
"denomUnitsSelected": "Participants",
"description": "Overall Survival (OS) is defined as the time from randomization to death due to any cause.\nData collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Randomization to death from any cause, through till the end of the study (2 years after the last participant is enrolled).",
"title": "Overall Survival (OS)",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2022-05",
"denomUnitsSelected": "Participants",
"description": "An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment.\nAn Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.\nPreexisting conditions which worsen during a study are also considered as Adverse Events.\nData collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.",
"reportingStatus": "NOT_POSTED",
"timeFrame": "Baseline up until 28 days after the last dose of study drug (venetoclax or fulvestrant, whichever is later).",
"title": "Percentage of Participants With Adverse Events (AEs)",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2022-05",
"denomUnitsSelected": "Participants",
"description": "The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received.\nDescriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.\nData collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.",
"reportingStatus": "NOT_POSTED",
"timeFrame": "At pre-defined intervals from Cycle 1, Day 1, through till the end of treatment (2 years after the last participant is enrolled).",
"title": "Plasma Concentrations of Venetoclax at Specified Timepoints",
"type": "SECONDARY"
},
{
"anticipatedPostingDate": "2022-05",
"denomUnitsSelected": "Participants",
"description": "The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received.\nDescriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.\nData collection is still ongoing and the results will be disclosed within 1 year from the Study Completion Date.",
"reportingStatus": "NOT_POSTED",
"timeFrame": "At pre-defined intervals from Cycle 1, Day 1, through till the end of treatment (2 years after the last participant is enrolled).",
"title": "Plasma Concentrations of Fulvestrant at Specified Timepoints",
"type": "SECONDARY"
}
]
},
"participantFlowModule": {
"groups": [
{
"description": "Participants were administered Venetoclax 800mg orally once daily (QD) and Fulvestrant 500mg intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "FG000",
"title": "Venetoclax + Fulvestrant"
},
{
"description": "Participants were administered Fulvestrant 500mg only intramuscularly (IM) on Day 1 and 15 of Cycle 1 and Day 1 of subsequent cycles (Cycle length = 28 days).",
"id": "FG001",
"title": "Fulvestrant"
}
],
"periods": [
{
"dropWithdraws": [
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "18"
},
{
"groupId": "FG001",
"numSubjects": "9"
}
],
"type": "Death"
},
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "0"
},
{
"groupId": "FG001",
"numSubjects": "1"
}
],
"type": "Lost to Follow-up"
},
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "1"
},
{
"groupId": "FG001",
"numSubjects": "1"
}
],
"type": "Physician Decision"
},
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "3"
},
{
"groupId": "FG001",
"numSubjects": "1"
}
],
"type": "Withdrawal by Subject"
},
{
"reasons": [
{
"groupId": "FG000",
"numSubjects": "29"
},
{
"groupId": "FG001",
"numSubjects": "40"
}
],
"type": "Ongoing in study"
}
],
"milestones": [
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "51"
},
{
"groupId": "FG001",
"numSubjects": "52"
}
],
"type": "STARTED"
},
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "0"
},
{
"groupId": "FG001",
"numSubjects": "0"
}
],
"type": "COMPLETED"
},
{
"achievements": [
{
"groupId": "FG000",
"numSubjects": "51"
},
{
"groupId": "FG001",
"numSubjects": "52"
}
],
"type": "NOT COMPLETED"
}
],
"title": "Overall Study"
}
],
"preAssignmentDetails": "A total of 103 participants were randomized in this study.\nOf these, 101 participants received at least one dose of any study drug.",
"recruitmentDetails": "The study was conducted at 38 centers in 5 countries."
}
}
},
{
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"annotationModule": {
"unpostedAnnotation": {
"unpostedEvents": [
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"date": "2021-08-11",
"type": "RESET"
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],
"unpostedResponsibleParty": "Hoffmann-La Roche"
}
}
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{
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"path": "/documentSection",
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"largeDocumentModule": {
"largeDocs": [
{
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"filename": "Prot_SAP_000.pdf",
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"hasSap": true,
"label": "Study Protocol and Statistical Analysis Plan",
"size": 2182942,
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"uploadDate": "2021-07-20T05:12"
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"review_question": "What source document explains this registry amendment, and does it change interpretation of the trial record?",
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