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.
* 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
63
Capsules (30-40 mg) taken orally twice a day on days 1-7 of each 28 day cycle
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
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Objective Response Rate (ORR) of ABT-888 and Temozolomide (TMZ) in Metastatic Breast Cancer
Objective response rate (ORR) is defined as the percentage of enrolled patients who have a partial or complete response per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 guidelines. A partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A complete response is defined as disappearance of all target lesions, with any pathological lymph nodes (whether target or non-target) reduced in short axis to \<10 mm.
Time frame: 2 years
Progression Free Survival
Progression free survival is defined as the length of time from enrollment until disease progression, death, or date of last patient contact. Progressive disease was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progressive disease is defined as at least a 20% increase (at least 5 mm) in the sum of the LD of target lesions in comparison with the lowest sum achieved on study or the appearance of one or more new lesions, and/or unequivocal progression of non-target lesions.
Time frame: 5 years
Clinical Benefit Rate
Clinical benefit rate (CBR) is defined as the percentage of patients who achieve a partial or complete response or stable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. A partial response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A complete response is defined as disappearance of all target lesions, with any pathological lymph nodes (whether target or non-target) reduced in short axis to \<10 mm. Progressive disease is defined as at least a 20% increase (at least 5 mm) in the sum of the LD of target lesions in comparison with the lowest sum achieved on study or the appearance of one or more new lesions, and/or unequivocal progression of non-target lesions.
Time frame: Four months
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