This is a Phase 1, dose escalation trial evaluating the tolerability, pharmacokinetics, and pharmacodynamics of ABT-767 in subjects with advanced Breast Cancer 1 or 2 gene (BRCA1 or BRCA2)-mutated solid tumors and high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
This is a Phase 1, dose escalation trial evaluating the tolerability, pharmacokinetics, and pharmacodynamics of ABT-767 in subjects with advanced BRCA1 or BRCA2-mutated solid tumors and high grade serous ovarian, fallopian tube, or primary peritoneal cancer. ABT-767 is a potent oral inhibitor of the enzymes poly (ADP-ribose) polymerase 1 and 2 (PARP-1 and PARP-2). Malignancies with deficiencies in homologous repair, such as BRCA-1 and BRCA-2 deficient tumors, are more dependent on PARP for deoxyribonucleic acid (DNA) repair than normal cells and, thus, are thought to be more sensitive to PARP inhibition. The study design is a single-arm dose escalation study to determine dose-limiting toxicities, maximum tolerated dose and the recommended Phase 2 dose (RPTD) of orally administered ABT-767 in subjects with BRCA mutations and malignancies. In order to further evaluate the safety and tolerability of ABT-767 at the RPTD, 20 additional subjects will be enrolled in an expanded safety cohort consisting of BRCA1- or BRCA2-mutated Breast cancer and Ovarian cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
93
ABT-767 once or twice daily for a 28 day cycle
Univ Med Center Groningen
Groningen, Netherlands
Univ Med Ctr, St. Radboud
Nijmegen, Netherlands
Erasmus Medisch Centrum
Rotterdam, Netherlands
Pharmacokinetic profile
Blood samples for pharmacokinetics of ABT-767 will be collected at designated time points
Time frame: Various time points from Cycle 1 Day -4 to Day 8
Safety (number of subjects with adverse events and/or dose limiting toxicities)
Adverse events, laboratory results, physical exams and vital signs will be evaluated throughout the study.
Time frame: Weekly for the first two months, every other week for the third month, and monthly there after. An expected average is 5 months.
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