ABT-888 in Patients With Refractory Solid Tumors or Hematologic Cancer

Phase 1

Completed

• Conditions: Leukemia; Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

• Registration Number: NCT00387608
• Lead Sponsor: National Institutes of Health Clinical Center (CC)

Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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.

Secondary

* 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 Timeline

• Study Start: 2006-06
• Study First Submitted: 2006-10-12
• Study First Submitted QC: 2006-10-12
• Study First Posted: 2006-10-13
• Primary Completion: 2008-02
• Study Completion: 2009-04
• Status Verified: 2012-03
• Last Update Submitted: 2012-03-14
• Last Update Posted: 2012-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in tumor poly (ADP-ribose) (PAR) levels from baseline to 3-6 hours after ABT-888 administration
Pharmacokinetics

Secondary Outcome Measures

Name	Time	Method
Safety of administering 1 dose of ABT-888
Changes in PAR levels in peripheral blood mononuclear cells from baseline to after ABT-888 administration

Trial Locations

Locations (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office; 🇺🇸 Bethesda, Maryland, United States