Veliparib With or Without Mitomycin C in Treating Patients With Metastatic, Unresectable, or Recurrent Solid Tumors

Solid Neoplasm Clinical Trial

Official title: ABT-888 as Monotherapy and in Combination With Mitomycin C in Patients With Solid Tumors With Deficiency in Homologous Recombination Repair

Status Completed

Clinical Trial Summary

This phase I trial studies the side effects and best dose of veliparib when given with or without mitomycin C in treating patients with solid tumors that have spread to other places in the body, cannot be removed by surgery or have come back. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib together with mitomycin C may kill more tumor cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

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 poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor ABT-888 (veliparib) as protracted monotherapy.

III. To establish the safety and practicality of treating patients with FA deficient tumors with the combination of mitomycin C (MMC) 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 trials.

SECONDARY OBJECTIVES:

I. To evaluate for germ-line FA repair deficiency and BRCA mutations in peripheral blood mononuclear (PBMC) in patients receiving ABT-888 treatment.

II. To evaluate in PBMC samples for foci produced by the histone variant gamma-H2A histone family, member X (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 deoxyribonucleic acid (DNA) double strand breaks.

III. Quantify the number of patients with antitumor responses.

OUTLINE: This is a dose-escalation study of veliparib. Patients are assigned to 1 of 2 treatment arms.

ARM I: Patients receive veliparib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive veliparib PO BID on days 1-7, 1-14, or 1-21. 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.

After completion of study treatment, patients are followed up for 12 weeks. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Solid Neoplasm

• NCT number: NCT01017640
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 1
• Start date: October 2009