ABT-888 Plus Metronomic Cyclophosphamide to Treat Cancer

Summary

Background: * Cyclophosphamide (CP) is a drug approved by the Food and Drug Administration for the treatment of certain cancers. It works by causing DNA damage, resulting in cell death, including cancer cells. * ABT-888 is an experimental drug that has been given to a small number of patients. It works by preventing DNA repair in tumor cells. Objectives: * To test the safety of the combination of ABT-888 and CP, and to determine the dose of each drug that can be given together to patients with cancer. * To see how the body handles ABT-888 when given together with CP * To evaluate the anti-tumor response of the drug combination. Eligibility: * Adults with solid tumors or lymphoid cancers (lymphoma and chronic lymphocytic leukemia) whose disease does not respond to standard treatments. Design: * Patients take ABT-888 by mouth once a day for 7, 14 or 21 days, depending on the dose level assigned to the individual patient. * Patients take CP by mouth once a day every day in 21-day cycles. (Some patients take CP for 14 days only.) * Patients undergo tests and procedures periodically during the study, including: * Clinic visit and physical examination at the beginning of each cycle * Blood and urine tests, electrocardiogram, measurement of vital signs * CT scans, MRI scans or ultrasound tests to check the response of the tumor to treatment * Tumor biopsies (optional) * Bone marrow aspiration and biopsy

Timeline

Start

2008-12-03

Primary completion

2012-07-03

Completion

2012-07-03

Publications

• Background Alderson T. New targets for cancer chemotherapy--poly(ADP-ribosylation) processing and polyisoprene metabolism. Biol Rev Camb Philos Soc. 1990 Nov;65(4):623-41. doi: 10.1111/j.1469-185x.1990.tb01240.x. No abstract available.
• Background Ame JC, Rolli V, Schreiber V, Niedergang C, Apiou F, Decker P, Muller S, Hoger T, Menissier-de Murcia J, de Murcia G. PARP-2, A novel mammalian DNA damage-dependent poly(ADP-ribose) polymerase. J Biol Chem. 1999 Jun 18;274(25):17860-8. doi: 10.1074/jbc.274.25.17860.
• Background Ame JC, Spenlehauer C, de Murcia G. The PARP superfamily. Bioessays. 2004 Aug;26(8):882-93. doi: 10.1002/bies.20085.

Drugs

Indications