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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 0 Pharmacokinetic, Pharmacodynamic Study of ABT-888, an Inhibitor of Poly (ADP-ribose) Polymerase (PARP), in Refractory Solid Tumors and Lymphoid Malignancies

Conditions
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Leukemia, Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: veliparib
* Other: pharmacological study
* Procedure: biopsy


Participation Criteria
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Eligibility Criteria
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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 PRIOR CONCURRENT THERAPY: At least 2 weeks since prior radiation therapy or surgery and recovered At least 2 weeks since other prior therapy and recovered No concurrent antiretroviral therapy for HIV-positive patients No concurrent lung, liver, or mediastinal lymph node biopsies No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: veliparib|nan|
|Other: pharmacological study|nan|
|Procedure: biopsy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tumor poly (ADP-ribose) (PAR) levels from baseline to 3-6 hours after ABT-888 administration |  |  | 
| Pharmacokinetics |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of administering 1 dose of ABT-888 |  |  | 
| Changes in PAR levels in peripheral blood mononuclear cells from baseline to after ABT-888 administration |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific, refractory chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma