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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00387608
First received: October 12, 2006
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Change in tumor poly (ADP-ribose) (PAR) levels from baseline to 3-6 hours after ABT-888 administration [ Designated as safety issue: No ]
  • Pharmacokinetics [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of administering 1 dose of ABT-888 [ Designated as safety issue: Yes ]
  • Changes in PAR levels in peripheral blood mononuclear cells from baseline to after ABT-888 administration [ Designated as safety issue: No ]

Estimated Enrollment: 23
Study Start Date: June 2006
Study Completion Date: April 2009
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00387608

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Principal Investigator: Shivaani Kummar, MD NCI - Medical Oncology Branch
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00387608     History of Changes
Obsolete Identifiers: NCT00347633
Other Study ID Numbers: 060172, 06-C-0172, NCI-P6890, CDR0000487701
Study First Received: October 12, 2006
Last Updated: March 14, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
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

Additional relevant MeSH terms:
Leukemia
Lymphoma
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2014