Clinical trial NCT01009788
Conditions: Breast Cancer Metastatic Breast Cancer BRCA1 Gene Mutation brca2 Gene Mutation
Keywords: ABT-888 temozolomide TMZ
Sponsor: Steven J Isakoff, MD, PhD
Start date: 2009-11-01; Completion date: 2015-09-01
Enrollment: 63 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this research study is to find out if the combination of ABT-888 and temozolomide is safe and effective in treating patients with metastatic breast cancer. ABT-888 works by obstructing a DNA enzyme called poly (ADP-ribose) polymerase (PARP) which helps repair cancer cells damaged by chemotherapy. By blocking the PARP enzyme, the cancer cells are unable to repair themselves and as a result die. The other drug in this study is temozolomide. Temozolomide is designed to damage DNA in order to prevent cancer cells from reproducing. Because PARP inhibitors, such as ABT-888, prevent cancer cells from repairing their own DNA, they enhance the potential of chemotherapy therapy like temozolomide to induce cell death. The combination of ABT-888 and temozolomide has been used in a clinical trial for treatment of other cancers and information for this research study suggests that the combination may help to inhibit growth in breast cancer.

ONLY THE EXPANSION COHORT BELOW IS RECRUITING:

BRCA CARRIER EXPANSION COHORT: The purpose of the expansion cohort is to further evaluate the activity and safety of this combination in BRCA mutation carriers with metastatic breast cancer.

Detailed description:
* Each treatment cycle lasts 28 days. Participants will be given a supply of ABT-88 in the form of capsules which they will take twice daily on days 1-7 of each cycle. Temozolomide is also in capsule form and will be taken once daily on days 1-5 of each cycle.
* Participants will come into the clinic on day 1 of each cycle and will have the following tests and procedures performed: physical examination, vital signs and blood tests.
* On day 15 of cycles 1 and 2 and day 22 of each cycle, participants will have blood work done.
* An assessment fo the tumor by CT scan of the participants chest, abdomen and pelvis will be done every 2 cycles.

Arms: arm 1: Primary cohort included patients unselected for BRCA1/2 mutations or breast cancer subtype.

Combination therapy with temozolomide and veliparib (28 day cycle) Veliparib 30-40 mg orally twice/day days 1-7 Temozolomide 150 mg/m\^2 orally once daily days 1-5, increased to 200 mg/m\^2 starting cycle 2 as tolerated arm 2: Expansion cohort included patients with BRCA1/2 deleterious mutations.

Combination therapy with temozolomide and veliparib (28 day cycle) Veliparib 30 mg orally twice/day days 1-7 Temozolomide 150 mg/m\^2 orally once daily days 1-5, increased to 200 mg/m\^2 starting cycle 2 as tolerated
Interventions: intervention 1: ABT-888 intervention 2: temozolomide
Intervention descriptions: intervention 1: Capsules (30-40 mg) taken orally twice a day on days 1-7 of each 28 day cycle intervention 2: Capsules (150 mg/m\^2 initially, and 200 mg/m\^2 starting cycle 2 if tolerated) taken orally once a day on days 1 through 5 of a 28 day cycle

Protocol documents:
Prot_SAP_000.pdf: