ABT-888 in Patients With Refractory Solid Tumors or Hematologic Cancer
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|ClinicalTrials.gov Identifier: NCT00387608|
Recruitment Status : Completed
First Posted : October 13, 2006
Last Update Posted : March 15, 2012
RATIONALE: ABT-888 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Collecting and storing samples of blood from patients with cancer to study in the laboratory may help doctors learn more about the ways a patient's body handles the drug.
PURPOSE: This early phase I trial is studying the side effects and best dose of ABT-888 in patients with refractory solid tumors or hematologic cancer.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Lymphoma Unspecified Adult Solid Tumor, Protocol Specific||Drug: veliparib Other: pharmacological study Procedure: biopsy||Phase 1|
- Determine the dose-range at which ABT-888 inhibits poly (ADP-ribose) polymerase (PARP) in tumor samples and in peripheral blood mononuclear cells (PBMCs) in patients with refractory solid tumors or lymphoid malignancies.
- Determine the pharmacokinetics of ABT-888.
- Determine the time course of PARP inhibition in PBMCs by ABT-888.
- Determine the safety of administering 1 dose of ABT-888 in these patients.
OUTLINE: This is a dose-finding study.
Patients receive oral ABT-888 once on day 1.
Cohorts of 3 patients receive escalating doses of ABT-888 until significant tumor poly (ADP-ribose) polymerase (PARP) inhibition is observed in 3 of 3 patients at 2 dose levels. Significant PARP inhibition is defined as ≥ 0.69 reduction on the log scale in poly (ADP-ribose) level from baseline to 3-6 hours after ABT-888 administration (with 90% confidence that it is not due to chance variation).
Patients undergo peripheral blood collection at baseline and periodically after ABT-888 administration for PARP inhibition, pharmacokinetic, and pharmacodynamic studies. Once significant PARP inhibition is observed in 1 of 3 patients, subsequently enrolled patients also undergo tumor biopsy* at baseline and 3-6 hours or 21-27 hours after ABT-888 administration to determine PARP inhibition in tumor tissue.
NOTE: *Patients with chronic lymphocytic leukemia undergo peripheral blood collection instead of biopsy.
After completion of ABT-888 administration, patients are followed for 7 days.
PROJECTED ACCRUAL: A total of 23 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||23 participants|
|Masking:||None (Open Label)|
|Official Title:||A Phase 0 Pharmacokinetic, Pharmacodynamic Study of ABT-888, an Inhibitor of Poly (ADP-ribose) Polymerase (PARP), in Refractory Solid Tumors and Lymphoid Malignancies|
|Study Start Date :||June 2006|
|Actual Primary Completion Date :||February 2008|
|Actual Study Completion Date :||April 2009|
- Change in tumor poly (ADP-ribose) (PAR) levels from baseline to 3-6 hours after ABT-888 administration
- Safety of administering 1 dose of ABT-888
- Changes in PAR levels in peripheral blood mononuclear cells from baseline to after ABT-888 administration
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00387608
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|Principal Investigator:||Shivaani Kummar, MD||NCI - Medical Oncology Branch|