| ID | Type | Description | Link |
|---|---|---|---|
| 06-C-0172 | |||
| NCI-P6890 | |||
| CDR0000487701 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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.
OBJECTIVES:
Primary
Secondary
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.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| veliparib | Drug | |||
| pharmacological study | Other | |||
| biopsy | Procedure |
| Measure | Description | Time Frame |
|---|---|---|
| Change in tumor poly (ADP-ribose) (PAR) levels from baseline to 3-6 hours after ABT-888 administration | ||
| Pharmacokinetics |
| 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 |
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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
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:
No psychiatric illness or social situations that would limit study compliance
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Shivaani Kummar, MD | NCI - Medical Oncology Branch | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda | Maryland | 20892-1182 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19364967 | Result | Kummar S, Kinders R, Gutierrez ME, Rubinstein L, Parchment RE, Phillips LR, Ji J, Monks A, Low JA, Chen A, Murgo AJ, Collins J, Steinberg SM, Eliopoulos H, Giranda VL, Gordon G, Helman L, Wiltrout R, Tomaszewski JE, Doroshow JH. Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies. J Clin Oncol. 2009 Jun 1;27(16):2705-11. doi: 10.1200/JCO.2008.19.7681. Epub 2009 Apr 13. |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D008224 | Lymphoma, Follicular |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C521013 | veliparib |
| D001706 | Biopsy |
| ID | Term |
|---|---|
| D003581 | Cytodiagnosis |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008228 | Lymphoma, Non-Hodgkin |
| D003933 | Diagnosis |
| D013048 | Specimen Handling |
| D003949 | Diagnostic Techniques, Surgical |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |