A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2-Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer
A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2-Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer
The primary objective of the study is to assess the progression-free survival (PFS) of veliparib in combination with carboplatin and paclitaxel (C/P) compared to placebo plus C/P in participants with a Breast Cancer Gene 1 or 2 (BRCA1; BRCA2) mutation in Human Epidermal Growth Factor Receptor 2 (HER2)-negative metastatic or locally advanced unresectable breast cancer. The secondary objectives of the study are to assess overall survival (OS), clinical benefit rate (CBR) through the end of Week 24, objective response rate (ORR) and PFS on subsequent therapy (PFS2) in participants treated with veliparib in combination with C/P versus placebo in combination with C/P.
This is a Phase 3, randomized, double-blind, multinational, multicenter study to evaluate the efficacy and tolerability of veliparib in combination with C/P compared to placebo in combination with C/P in participants with a BRCA1 or BRCA2 mutation, as documented by the Sponsor core laboratory, with HER2-negative metastatic or locally advanced unresectable breast cancer who received no more than 2 prior lines of cytotoxic therapy for metastatic disease. For the purposes of eligibility, HER2-negative status was based on the most recent tumor biopsy. Participants were randomized in a 2:1 ratio, with a total of approximately 500 participants planned to be randomized. Veliparib 120 mg/placebo twice a day (BID) was dosed Days -2 through 5 with carboplatin target area under the concentration-time curve (AUC) 6 administered on Day 1 and paclitaxel 80 mg/m2 administered weekly on Days 1, 8, and 15 of each 21-day cycle.
Safety and efficacy data through the prespecified primary analysis cutoff date of 05 April 2019 are included in the interim analysis.
Inclusion Criteria:
Exclusion Criteria:
More than two prior lines of cytotoxic chemotherapy (e.g., gemcitabine, doxorubicin, capecitabine) for metastatic disease.
Progressed or recurred within 12 months of completing platinum therapy or received > 1 prior line of platinum therapy for breast cancer in any setting (adjuvant, neoadjuvant, or metastatic).
Prior therapy with Poly(ADP-ribose)-Polymerase (PARP) inhibitors.
Prior taxane therapy administered for the treatment of metastatic breast cancer with the below exceptions.
Known history of allergic reaction to cremophor-paclitaxel, carboplatin, Azo-Colourant Tartrazine (also known as FD&C Yellow 5 or E102), Azo-Colourant Orange Yellow-S (also known as FD&C Yellow 6 or E110) or known contraindications to any study supplied drug.
Active CNS metastases or leptomeningeal disease.
Fresno, California 93720, United States
Hershey, Pennsylvania 17033, United States
Berazategui, Buenos Aires 1884, Argentina
Minsk, 223040, Belarus
Bogota, Cundinamarca 110221, Colombia
Bogota, Cundinamarca 110231, Colombia
Montería, Departamento de Córdoba 230002, Colombia
Copenhagen Ø, Capital Region 2100, Denmark
Saint-Herblain, Loire-Atlantique 44805, France
Kaunas, 50161, Lithuania
Rzeszów, Podkarpackie Voivodeship 35-021, Poland
Lodz, Łódź Voivodeship 93-513, Poland
Vila Nova de Gaia, Porto District 4434-502, Portugal
Lisbon, 1649-035, Portugal
Bloemfontein, Free State 9301, South Africa
Seoul, Seoul Teugbyeolsi 03722, South Korea
Ankara, 06200, Turkey (Türkiye)
Dnipro, 49102, Ukraine
Poltava, 36011, Ukraine
Zaporizhia, 69040, Ukraine
Hull, East Riding Of Yorkshire HU3 2JZ, United Kingdom
Nottingham, Nottinghamshire NG5 1PB, United Kingdom