Veliparib With Carboplatin and Paclitaxel and as Continuation Maintenance Therapy in Adults With Newly Diagnosed Stage III or IV, High-grade Serous, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
- Histologic diagnosis of International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, with the appropriate tissue available for histologic evaluation.
- High-grade serous adenocarcinoma
- Willing to undergo testing for gBRCA.
- Adequate hematologic, renal, and hepatic function.
- Neuropathy (sensory and motor) less than or equal to Grade 1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Participants who undergo primary cytoreductive surgery must be entered between 1 and 12 weeks after surgery. Participants undergoing interval surgery must have a tumor sample confirming the histological diagnosis prior to enrollment.
- Participants with measurable disease or non-measurable disease are eligible. Participants may or may not have cancer-related symptoms.
- Participant has one of the following available for pharmacodynamic analyses including somatic BRCA testing: Archived diagnostic formalin-fixed paraffin embedded (FFPE) tumor tissue; or tumor tissue biopsy collected prior to Cycle 1 Day 1.
- Endometrioid adenocarcinoma, carcinosarcoma, undifferentiated carcinoma, mixed epithelial adenocarcinoma, adenocarcinoma not otherwise specified, mucinous adenocarcinoma, clear cell adenocarcinoma, low-grade serous adenocarcinoma, or malignant Brenner's tumor.
- Participants with synchronous primary endometrial cancer, or a past history of endometrial cancer unless all of the following conditions are met: endometrial cancer stage not greater than IA, no vascular or lymphatic invasion, no poorly differentiated subtypes including serous, clear cell, or other FIGO grade 3 lesions.
- Participants with any evidence of other invasive malignancy being present within the last 3 years (with the exception of non-melanoma skin cancer). Participants are also excluded if their previous cancer treatment contraindicates this protocol's therapy.
- Received prior radiotherapy to any portion of the abdominal cavity or pelvis.
- Received prior chemotherapy for any abdominal or pelvic tumor.
- Clinically significant uncontrolled condition(s).
- 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.
- History or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) within 6 months of Cycle 1 Day
Salt Lake City
Participants were randomized in a 1:1:1 ratio to one of three arms. Randomization in the
entire population was stratified according to the timing of surgery and residual disease
status (any residual disease after primary surgery vs. no residual disease after primary
surgery vs. interval surgery) and the paclitaxel schedule (weekly vs. every 3 -weeks), stage
of disease (III vs. IV), geographic region (Japan vs. North America and rest of world [ROW]),
and germline breast cancer susceptibility gene (BRCA) mutation status (positive versus
negative or Unknown).
Cytoreductive surgery could be performed before randomization and the initiation of study
treatment (primary) or after 3 cycles of study treatment (interval). The weekly or
every-3-week paclitaxel schedule and the choice of primary or interval cytoreductive surgery
were determined at the discretion of the investigator.
The primary objective was evaluated in the BRCA-deficient cohort, participants with
homologous recombination deficiency (HRD), and the intention-to-treat (ITT) population. These
populations were sequentially inclusive, with the HRD population including the BRCA-deficient
population, and the ITT population including the HRD and BRCA-deficient populations. The
BRCA-deficient population was defined as participants with either a germline (gBRCA) and/or
tissue-based (tBRCA) deleterious or suspected deleterious mutation in BRCA1 or BRCA2
confirmed by centralized testing. The HRD population was defined as participants with HRD
tumors based on HRD score or presence of a deleterious or suspected deleterious mutation in
BRCA1 or BRCA2 as determined by centralized testing.
Trial Phase Phase III
Trial Type Treatment
- Primary ID M13-694
- Secondary IDs NCI-2015-01623, 2014‐005070‐11, 2014-005070-11
- Clinicaltrials.gov ID NCT02470585