Study Evaluating Efficacy And Tolerability Of Veliparib in Combination With Temozolomide (TMZ) or In Combination With Carboplatin and Paclitaxel Versus Placebo in Participants With Breast Cancer Gene (BRCA)1 and BRCA2 Mutation and Metastatic Breast Cancer

Phase 2

Completed

• Conditions: Metastatic Breast Cancer
• Interventions: Drug: Placebo; Drug: Veliparib; Drug: Carboplatin; Drug: Temozolomide; Drug: Paclitaxel

• Registration Number: NCT01506609
• Lead Sponsor: AbbVie

Brief Summary

The primary objective of the study is to assess the progression-free survival (PFS) of oral veliparib in combination with TMZ or in combination with carboplatin and paclitaxel compared to placebo plus carboplatin and paclitaxel in subjects with BRCA1 or BRCA2 mutation and locally recurrent or metastatic breast cancer.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-01-06
• Study First Submitted QC: 2012-01-09
• Study First Posted: 2012-01-10
• Study Start: 2012-01-23
• Primary Completion: 2018-12-13
• Disposition First Submitted: 2019-11-12
• Disposition First Submitted QC: 2019-11-12
• Disposition First Posted: 2019-11-15
• Study Completion: 2020-09-02
• Status Verified: 2021-09
• Results First Submitted: 2021-09-27
• Results First Submitted QC: 2021-09-27
• Last Update Submitted: 2021-09-27
• Results First Posted: 2021-10-25
• Last Update Posted: 2021-10-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 294

Inclusion Criteria

• Histologically or cytologically confirmed breast cancer that is either locally recurrent or metastatic.
• Locally recurrent disease must not be amenable to surgical resection or radiation with curative intent.
• Must have a documented deleterious Breast Cancer Gene BRCA1 or BRCA2 germline mutation.
• If Human Epidermal Growth Factor Receptor (HER2) positive, subjects must have received and progressed on at least one prior standard HER2 directed therapy or the subject must be ineligible to receive anti-HER2 therapy.
• Measurable or non-measurable (but radiologically evaluable) disease by RECIST (Response Evaluation Criteria in Solid Tumors) criteria 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
• Subject must have adequate bone marrow, renal and hepatic function.
• Subject must not be pregnant or plan to conceive a child.

Exclusion Criteria

• Received anticancer agent(s) or an investigational agent within 21 days prior to C1D1, or radiotherapy within 28 days prior Cycle 1 Day 1.
• More than 2 prior lines of cytotoxic chemotherapy.
• Prior treatment of breast cancer with temozolomide, a platinum agent, or a Poly (ADP ribose) Polymerase (PARP) inhibitor.
• Prior taxane therapy for metastatic breast cancer.
• A history of or evidence of brain metastases or leptomeningeal disease.
• A history of uncontrolled seizure disorder.
• Pre-existing neuropathy from any cause in excess of Grade 1.
• Known history of allergic reaction to cremophor/paclitaxel.
• Clinical significant uncontrolled conditions, active infection, myocardial infarction, stroke, or transient ischemic attack, psychiatric illness/social situations that would limit compliance.
• Pregnant or breastfeeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo with Carboplatin and Paclitaxel	Placebo	Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle.
Placebo with Carboplatin and Paclitaxel	Carboplatin	Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle.
Veliparib with Temozolomide	Veliparib	Veliparib 40 mg twice daily (BID) Days 1 through 7 plus TMZ 150 to 200 mg/m\^2 QD Days 1 through 5 in each 28-day cycle.
Veliparib with Temozolomide	Temozolomide	Veliparib 40 mg twice daily (BID) Days 1 through 7 plus TMZ 150 to 200 mg/m\^2 QD Days 1 through 5 in each 28-day cycle.
Placebo with Carboplatin and Paclitaxel	Paclitaxel	Placebo BID Days 1 through 7 plus carboplatin target area under the curve (mg•min/mL) (AUC) 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle.
Veliparib with Carboplatin and Paclitaxel	Veliparib	Veliparib 80 mg BID Days 1 through 7 plus carboplatin target AUC 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle.
Veliparib with Carboplatin and Paclitaxel	Carboplatin	Veliparib 80 mg BID Days 1 through 7 plus carboplatin target AUC 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle.
Veliparib with Carboplatin and Paclitaxel	Paclitaxel	Veliparib 80 mg BID Days 1 through 7 plus carboplatin target AUC 6 administered on Day 3 of each 21-day cycle and paclitaxel 175 mg/m\^2 administered on Day 3 of each 21-day cycle.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for PFS was 34 months.	PFS is defined as the number of months from the date the participant was randomized to the date of radiographic progression as determined by the central imaging center, or to the date of all cause deaths within 63 days of last tumor assessment if disease progression was not reached.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From Cycle 1 Day 1 until participant's death or 3 years post discontinuation (data cutoff date: 04 March 2016); maximum duration of follow up for OS was 72 months.	Time to death for a given participant was defined as the number of months from the day the participant is randomized to the date of the participant's death. All events of death were included, regardless of whether the event occurs while the participant was still taking study drug, or after the participant discontinued study drug. If a participant had not died, then the data will be censored at the date when the participant was last known to be alive.
Clinical Benefit Rate (CBR) at Week 18	Week 18	CBR: percentage of participants who were progression-free at 18 weeks, defined as complete response (CR), partial response (PR), stable disease (SD) or non-CR/non-disease progression (PD) per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1.; CR: The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 0 mm. PR: \>= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters (SOD). PD: \>= 20% increase in the SOD of target lesions, taking as reference the smallest SOD recorded since the treatment started (baseline or after) or the appearance of \>=1 new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD since the treatment started (baseline or after).
Objective Response Rate (ORR)	Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for ORR was 34 months.	The objective response rate, defined as percentage of participants with a confirmed CR or PR based on RECIST 1.1 criteria. CR: The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 0 mm. PR: \>= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline SODs.
Change From Baseline at Week 18 in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Subscale Score	Baseline, Week 18	EORTC QLQ-CIPN20 sensory subscale score was calculated following the standard scoring algorithm, transformed to a 0 (low quality of life) to 100 (best quality of life) scale. A positive change from baseline indicates improvement.

Trial Locations

Locations (120)

University of Alabama at Birmingham - Main /ID# 62994; 🇺🇸 Birmingham, Alabama, United States

Banner MD Anderson Cancer Ctr /ID# 118695; 🇺🇸 Gilbert, Arizona, United States

University of Arkansas for Medical Sciences /ID# 60750; 🇺🇸 Little Rock, Arkansas, United States

Moore UC San Diego Cancer Center /ID# 60754; 🇺🇸 La Jolla, California, United States

The Angeles Clinic and Researc /ID# 60743; 🇺🇸 Los Angeles, California, United States

Stanford University School of Med /ID# 65488; 🇺🇸 Stanford, California, United States

Cedars-Sinai Medical Center - West Hollywood /ID# 60760; 🇺🇸 West Hollywood, California, United States

Univ of Colorado Cancer Center /ID# 60751; 🇺🇸 Aurora, Colorado, United States

Lynn Cancer Institute, Boca /ID# 60749; 🇺🇸 Boca Raton, Florida, United States

Holy Cross Hospital /ID# 62995; 🇺🇸 Fort Lauderdale, Florida, United States

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