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

AbbVie294 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

294

Conditions

Metastatic Breast Cancer

Interventions

PlaceboDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

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

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

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.

Time frame: 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.

Secondary Outcomes

Overall Survival (OS)

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.

Time frame: 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.

Clinical Benefit Rate (CBR) at 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).

Time frame: Week 18

Objective Response Rate (ORR)

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.

Time frame: 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.

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

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.

Time frame: Baseline, Week 18