ABT-888 in Patients With Refractory Solid Tumors or Hematologic Cancer
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| ClinicalTrials.gov Identifier: NCT00387608 |
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Recruitment Status :
Completed
First Posted : October 13, 2006
Last Update Posted : March 15, 2012
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Leukemia Lymphoma Unspecified Adult Solid Tumor, Protocol Specific | Drug: veliparib Other: pharmacological study Procedure: biopsy | Phase 1 |
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 Type : | Interventional (Clinical Trial) |
| Estimated 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 : | 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
- Pharmacokinetics
- Safety of administering 1 dose of ABT-888
- Changes in PAR levels in peripheral blood mononuclear cells from baseline to after ABT-888 administration
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Histologically confirmed malignancy, meeting 1 of the following criteria:
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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
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- 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
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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
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 |
| ClinicalTrials.gov Identifier: | NCT00387608 |
| Obsolete Identifiers: | NCT00347633 |
| Other Study ID Numbers: |
060172 06-C-0172 NCI-P6890 CDR0000487701 |
| First Posted: | October 13, 2006 Key Record Dates |
| Last Update Posted: | March 15, 2012 |
| Last Verified: | March 2012 |
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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 |
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Lymphoma Leukemia Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders |
Immune System Diseases Veliparib Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |