ABT-888 and Cyclophosphamide in Treating Patients With Solid Tumors or Lymphoma That Did Not Respond to Previous Therapy
Recruitment status was Active, not recruiting
RATIONALE: ABT-888 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving ABT-888 together with cyclophosphamide may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of ABT-888 when given together with cyclophosphamide in treating patients with solid tumors or lymphoma that did not respond to previous therapy.
Unspecified Adult Solid Tumor, Protocol Specific
Other: immunologic technique
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
|Study Design:||Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of ABT-888 in Combination With Metronomic Cyclophosphamide in Adults With Refractory Solid Tumors and Lymphomas|
- Maximum tolerated dose of ABT-888 when administered in combination with metronomic cyclophosphamide [ Designated as safety issue: Yes ]
- Safety [ Designated as safety issue: Yes ]
- Pharmacokinetics of ABT-888 [ Designated as safety issue: No ]
- Clinical response [ Designated as safety issue: No ]
- Level of PARP inhibition [ Designated as safety issue: No ]
- Amount of γ-H2AX induction [ Designated as safety issue: No ]
|Study Start Date:||December 2008|
- Establish the safety and tolerability of ABT-888 when administered in combination with metronomic cyclophosphamide in patients with refractory solid tumors or lymphoma.
- Establish the maximum tolerated dose of ABT-888 when administered in combination with metronomic cyclophosphamide in these patients.
- Evaluate the pharmacokinetics of ABT-888 when administered in combination with metronomic cyclophosphamide in these patients.
- Evaluate the antitumor response in these patients.
- Determine the effects of treatment on the level of PARP inhibition and γ-H2AX in blood and tumor samples from these patients.
OUTLINE: This is a multicenter, dose-escalation study of ABT-888.
Patients receive oral ABT-888 once daily for 7-21 days and oral cyclophosphamide once daily for 14 or 21 days. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Plasma samples are collected periodically for pharmacodynamic and pharmacokinetic analysis. Samples are analyzed for PAR concentration by immunoassay, γ-H2AX levels by immunocytochemistry, quantification of the γ-H2AX marker and co-localization markers via quantitative immunofluorescence analysis, and ABT-888 concentration by liquid chromatography/mass spectrometry.
After completion of study therapy, patients are followed for 30 days.
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010-3000|
|USC/Norris Comprehensive Cancer Center and Hospital|
|Los Angeles, California, United States, 90033|
|City of Hope Medical Group|
|Pasadena, California, United States, 91105|
|University of California Davis Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|United States, Pennsylvania|
|Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|UPMC Cancer Center at Magee-Womens Hospital|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Shivaani Kummar, MD||National Cancer Institute (NCI)|