A Study of ABT-888 in Combination With Temozolomide for Colorectal Cancer
People with colorectal cancer that cannot be cured by surgery are being asked to participate in this study.
The purpose of this study is to test the efficacy (effectiveness) of a new combination of drugs, ABT-888 and temozolomide for patients with colorectal cancer. Temozolomide acts by damaging deoxyribonucleic acid (DNA) in rapidly dividing cells, in other words, cancer cells. ABT-888 inhibits an enzyme called "PARP" which helps to fix damaged DNA. By inhibiting this enzyme, ABT-888 prevents cancer cells from repairing the damage caused by the temozolomide, and will hopefully increase the killing of cancer cells, and decrease the tumors in the body.
ABT-888 is an investigational or experimental anti-cancer agent that has not yet been approved by the Food and Drug Administration (FDA) for use in colorectal cancer.
This study will help find out what effects (good and bad) the combination of drugs, temozolomide and ABT-888 has on colorectal cancer.
This research is being done because it is not known if ABT-888 will increase the effectiveness of temozolomide for colorectal cancer.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of ABT-888, an Inhibitor of Poly(ADP-ribose) Polymerase (PARP) in Combination With Temozolomide in Patients With Heavily Pretreated, Metastatic Colorectal Cancer|
- Disease control rate defined as stable disease, partial response, or complete response according to the Response Evaluation Criteria in Solid Tumors (RECIST). [ Time Frame: 2 months ] [ Designated as safety issue: No ]
- Progression-free survival defines as the time in days from study study entry until progression or death [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Overall survival defined as the time in days from study entry until death [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Objective response rate defined as partial response or complete response according to RECIST criteria [ Time Frame: 2 months ] [ Designated as safety issue: No ]
- Safety as assessed by study drug exposure, adverse events,, serious adverse events, oncology-related events, deaths, and changes in laboratory determinations and vital sign parameters [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2009|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: ABT-888 and temozolomide
Temozolomide Days 1-5 and ABT-888 Days 1-7 of each 28-day cycle
Drug: Temozolomide and ABT-888
Temozolomide 150 mg/m2 once a day on Days 1-5 of each 28-day cycle ABT-888 40-mg orally BID on Days 1-7 of each 28-day cycle
We will initiate a single arm, open label Phase II study to test the clinical activity of ABT-888 and temozolomide in patients with metastatic colorectal cancer.
Treatment will continue weekly with restaging scans to be performed every 8 weeks. The trial will follow a Simon's two-stage optimal design. For the first stage, 21 patients will be accrued. If two (9.5%) or fewer of the 21 patients exhibit a partial or complete response with ABT-888 plus temozolomide, the agent will be rejected and the trial stopped. However, if at least 3 patients of the 21 (14%) exhibit a response in the first stage, then an additional 29 patients will be entered into the second stage, for a total of 50 patients in this phase II study. If 8 (16%) or more patients exhibit a response, then the treatment will be considered for further investigation. The sample sizes of 21 and 50 patients and the decision rules, in stages 1 and 2 respectively, are designed to differentiate a 25% overall response rate from a 10% overall response rate.
|United States, District of Columbia|
|Georgetown University Medical Center|
|Washington, District of Columbia, United States, 20008|
|Principal Investigator:||Michael J Pishvaian, MD, PhD||Georgetown University|