Phase II ABT-888 With Cyclophosphamide

Summary

Background: \- The experimental cancer treatment drug ABT-888 (Veliparib) works by preventing deoxyribonucleic acid (DNA) repair in tumor cells. Cyclophosphamide is a cancer treatment drug that works by causing DNA damage in cells, including cancer cells, resulting in cell death. However, because cyclophosphamide has strong and unpleasant side effects, researchers are interested in finding drugs that can be given in combination with cyclophosphamide that will allow a lower dose of cyclophosphamide to be given with similar effects. The combination of ABT-88 and cyclophosphamide may be an effective treatment for some types of cancer, such as certain kinds of breast or ovarian cancer and non-Hodgkin's lymphoma that often do not respond to standard therapies. Objectives: \- To evaluate the safety and effectiveness of ABT-888 and cyclophosphamide in ovarian and breast cancer and in non-Hodgkin's lymphoma that have not responded to standard treatments. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with (1) (Breast cancer 1/2) BRCA1/2 ovarian cancer, primary peritoneal or ovarian high-grade carcinoma, or fallopian tube cancer; (2) triple-negative breast cancer (not responsive to hormone-related therapy); or (3) low grade non-Hodgkin's lymphoma. Design: * Participants will be screened with a full medical history and physical examination, blood and urine tests, and tumor imaging studies. Participants will be divided into two groups with different treatment subgroups. * Group 1: Participants who have BRCA-positive ovarian cancer, primary peritoneal or ovarian high-grade serous carcinoma, or fallopian tube cancer * Participants will receive either the combination of ABT-888 and cyclophosphamide, or cyclophosphamide alone. * Participants will take the study drug by mouth once a day for 21-day cycles of treatment, and will keep a diary to record drug doses and any side effects. * Participants will have clinic visits with blood and urine tests, imaging studies, and other examinations on days 1, 2, 7, and 14 of cycle 1, and on the first day of all other cycles. * Group 2: Participants who have triple-negative breast cancer or non-Hodgkin's lymphoma * Participants will receive either the combination of ABT-888 and cyclophosphamide, or cyclophosphamide alone. * Participants will take the study drug by mouth once a day for 21-day cycles of treatment, and will keep a diary to record drug doses and any side effects. * Participants will have clinic visits with blood and urine tests, imaging studies, and other examinations on days 1, 2, 7, and 14 of cycle 1, and on the first day of all other cycles. * Participants receiving only cyclophosphamide who show signs of disease progression after tumor imaging studies can receive the combination of ABT-888 with cyclophosphamide. * Treatment will continue as long as participants tolerate the drugs and the disease does not progress.

Timeline

Start

2011-01-12

Primary completion

2014-12-31

Completion

2016-12-15

Publications

• Background Donawho CK, Luo Y, Luo Y, Penning TD, Bauch JL, Bouska JJ, Bontcheva-Diaz VD, Cox BF, DeWeese TL, Dillehay LE, Ferguson DC, Ghoreishi-Haack NS, Grimm DR, Guan R, Han EK, Holley-Shanks RR, Hristov B, Idler KB, Jarvis K, Johnson EF, Kleinberg LR, Klinghofer V, Lasko LM, Liu X, Marsh KC, McGonigal TP, Meulbroek JA, Olson AM, Palma JP, Rodriguez LE, Shi Y, Stavropoulos JA, Tsurutani AC, Zhu GD, Rosenberg SH, Giranda VL, Frost DJ. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007 May 1;13(9):2728-37. doi: 10.1158/1078-0432.CCR-06-3039.
• Background Shiobara M, Miyazaki M, Ito H, Togawa A, Nakajima N, Nomura F, Morinaga N, Noda M. Enhanced polyadenosine diphosphate-ribosylation in cirrhotic liver and carcinoma tissues in patients with hepatocellular carcinoma. J Gastroenterol Hepatol. 2001 Mar;16(3):338-44. doi: 10.1046/j.1440-1746.2001.02378.x.
• Background Tomoda T, Kurashige T, Moriki T, Yamamoto H, Fujimoto S, Taniguchi T. Enhanced expression of poly(ADP-ribose) synthetase gene in malignant lymphoma. Am J Hematol. 1991 Aug;37(4):223-7. doi: 10.1002/ajh.2830370402.
• Results Kummar S, Oza AM, Fleming GF, Sullivan DM, Gandara DR, Naughton MJ, Villalona-Calero MA, Morgan RJ Jr, Szabo PM, Youn A, Chen AP, Ji J, Allen DE, Lih CJ, Mehaffey MG, Walsh WD, McGregor PM 3rd, Steinberg SM, Williams PM, Kinders RJ, Conley BA, Simon RM, Doroshow JH. Randomized Trial of Oral Cyclophosphamide and Veliparib in High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers, or BRCA-Mutant Ovarian Cancer. Clin Cancer Res. 2015 Apr 1;21(7):1574-82. doi: 10.1158/1078-0432.CCR-14-2565. Epub 2015 Jan 14.
• Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.

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Indications