ABT-888 as Monotherapy and in Combination With Mitomycin C in Patients With Solid Tumors With Deficiency in Homologous Recombination Repair
I. To screen cancer patients across different histological sites to identify those with
functional defects in the Fanconi anemia (FA) pathway in their tumors.
II. To establish the safety and practicality of treating patients with FA-deficient tumors
with the PARP inhibitor ABT-888 as protracted monotherapy.
III. To establish the safety and practicality of treating patients with FA-deficient tumors
with the combination of mitomycin C and ABT-888.
IV. To select a dose of ABT-888 protracted monotherapy and a dose-schedule of the
combination of mitomycin C and ABT-888 in patients with FA deficient tumors for phase 2
I. To evaluate for germ line FA-repair deficiency and BRCA mutations in peripheral blood
mononuclear cell (PBMC) in patients receiving ABT-888 treatment.
II. To evaluate in PBMC samples for foci produced by the histone variant gamma-H2AX in
patients receiving Mitomycin C with or without ABT-888 in order to assess any possible
effect of ABT-888 in the cellular sensing and processing of Mitomycin C-induced DNA double
III. Quantify the number of patients with antitumor responses.
OUTLINE: This is a dose-escalation study of ABT-888. Patients are assigned to 1 of 2
GROUP I: Patients receive ABT-888 orally (PO) twice daily (BID) in the absence of disease
progression or unacceptable toxicity.
GROUP II: Patients receive ABT-888 PO BID on days 1-7, 1-14, 1-21, or 1-28. Patients also
receive mitomycin C intravenously (IV) over 10-20 minutes on day 1. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity. Blood and tissue
samples are collected periodically for further laboratory analysis, including BRCA mutation
analysis and H2AX and FancD2 activation analysis.
After completion of study treatment, patients are followed up for 12 weeks.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility of screening for Fanconi anemia (FA) deficiency across different tumor types, and that patients deficient in this pathway (no FancD2 foci formation in their tumors) exist in adequate number to justify further trials
Up to 3 years
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|
|Lombardi Comprehensive Cancer Center at Georgetown University||Washington, District of Columbia 20057|