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 (VELIA)

AbbVie

Status and phase: Terminated; Phase 3

Conditions: Ovarian Neoplasm; Ovarian Cancer

Treatments: Drug: Carboplatin; Other: Placebo to Veliparib; Drug: Paclitaxel; Drug: Veliparib

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT02470585

2014-005070-11 (EudraCT Number)

M13-694

Details and patient eligibility

About

The primary objective of the study was to evaluate whether progression-free survival (PFS) was prolonged with the addition of veliparib to standard platinum-based chemotherapy (carboplatin/paclitaxel [C/P]) and continued as maintenance therapy compared with chemotherapy alone.

Full description

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.

Enrollment: 1,140 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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.
2. High-grade serous adenocarcinoma
3. Willing to undergo testing for gBRCA.
4. Adequate hematologic, renal, and hepatic function.
5. Neuropathy (sensory and motor) less than or equal to Grade 1.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
7. 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.
8. Participants with measurable disease or non-measurable disease are eligible. Participants may or may not have cancer-related symptoms.
9. 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.

Exclusion criteria

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.
2. 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.
3. 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.
4. Received prior radiotherapy to any portion of the abdominal cavity or pelvis.
5. Received prior chemotherapy for any abdominal or pelvic tumor.
6. Clinically significant uncontrolled condition(s).
7. 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.
8. 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 1.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,140 participants in 3 patient groups

Placebo + Carboplatin + Paclitaxel -> Placebo

Active Comparator group

Description:

Participants will receive placebo to veliparib orally twice a day in combination with carboplatin/paclitaxel for six 21-day cycles followed by placebo monotherapy continuous dosing for an additional thirty 21-day cycles.

Treatment:

Drug: Paclitaxel

Other: Placebo to Veliparib

Drug: Carboplatin

Veliparib + Carboplatin + Paclitaxel -> Placebo

Experimental group

Description:

Participants will receive 150 mg veliparib orally twice a day in combination with carboplatin/paclitaxel for six 21-day cycles followed by placebo monotherapy continuous dosing for an additional thirty 21-day cycles.

Treatment:

Drug: Veliparib

Drug: Paclitaxel

Other: Placebo to Veliparib

Drug: Carboplatin

Veliparib + Carboplatin + Paclitaxel -> Veliparib

Experimental group

Description:

Participants will receive 150 mg veliparib orally twice a day in combination with carboplatin/paclitaxel for six 21-day cycles followed by 300/400 mg veliparib monotherapy orally twice a day for an additional thirty 21-day cycles.

Treatment:

Drug: Veliparib

Drug: Paclitaxel

Drug: Carboplatin