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

Sponsor

National Institutes of Health Clinical Center (CC) (NIH)

Overall Status

Completed

CT.gov ID

NCT00387608

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Unspecified Adult Solid Tumor, Protocol Specific	Drug: veliparib Other: pharmacological study Procedure: biopsy	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

23 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 :

Jun 1, 2006

Actual Primary Completion Date :

Feb 1, 2008

Actual Study Completion Date :

Apr 1, 2009

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed malignancy, meeting 1 of the following criteria:
Solid tumor that is refractory to ≥ 1 line of standard treatment OR for which no standard therapy is available
Must have ≥ 1 lesion amenable to percutaneous biopsy (for solid tumor patients enrolled after the initial phase of the study)
Chronic lymphocytic leukemia (CLL) or follicular lymphoma with no current indication for standard therapy OR disease that has failed ≥ 1 line of standard therapy
No disease-associated symptoms requiring immediate therapy or other interventions
Must be willing to undergo tumor biopsies* after the initial phase of the study NOTE: *Patients with CLL undergo peripheral blood collection instead of biopsy
No primary brain tumors, brain metastases, or leptomeningeal disease

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
Life expectancy ≥ 3 months
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
Bilirubin < 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Creatinine < 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
INR ≤ 1.4
PTT ≤ 36 seconds
Calcium (corrected) normal
Magnesium < 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 30 days after study completion
No history of seizures
No evidence of bleeding diathesis
No uncontrolled intercurrent illness including, but not limited to, any of the following:
Ongoing or active infection
Symptomatic congestive heart failure
Unstable angina pectoris
Cardiac arrhythmias
No psychiatric illness or social situations that would limit study compliance