Veliparib, Paclitaxel, and Carboplatin in Treating Patients with Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery and Liver or Kidney Dysfunction

Status: Temporarily Closed to Accrual

Description

This phase I trial studies the side effects and the best dose of veliparib when given together with paclitaxel and carboplatin in treating patients with solid tumors that are metastatic or cannot be removed by surgery and liver or kidney dysfunction. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib together with paclitaxel and carboplatin may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Patients must have histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, for which standard curative or palliative measures do not exist or are no longer effective, and for which there is expectation of response to the combination of carboplatin/paclitaxel (i.e., lung, ovarian, breast, melanoma, head and neck, endometrial, urothelial, testicular, esophageal, carcinoma of unknown primary); for indications not listed, eligibility based on disease must be verified by the principal investigator before they are considered
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 12 weeks
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8.0 g/dL
  • Patients with all degrees of renal dysfunction are allowed including patients on hemodialysis; patients with mild to severe hepatic dysfunction are allowed as defined below:
  • Total bilirubin =< 5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 10 x ULN
  • For patients with a recently placed biliary stent, patients should have consistent results within a hepatic group from two laboratory readings within 3 days apart, taken at least 10 days following biliary stent placement; for patients with a biliary stent placed over 2 months ago, no obstruction or blockage can have occurred within the last 2 months
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those whose adverse event due to agents administered more than 4 weeks earlier have not resolved or stabilized; patients who have been administered ABT-888 as part of a single or combination, phase 0 or I study, should not necessarily be excluded from participating in this study solely because of receiving prior ABT-888
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or other agents used in study
  • Peripheral neuropathy of severity greater than grade 1
  • Inability to take oral medications on a continuous basis
  • Evidence of bleeding diathesis
  • Patients with central nervous system (CNS) metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for at least 3 months and must be off steroid treatment prior to study enrollment
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ABT-888; these potential risks may also apply to other agents used in this study
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; however, HIV-positive patients without an acquired immune deficiency syndrome (AIDS)-defining diagnosis who are not receiving agents with the potential for pharmacokinetic (PK) interactions with ABT-888 may be eligible
  • Patients with both hepatic and renal dysfunction will also be excluded
  • Patients who received and progressed on the combination of carboplatin/paclitaxel will not be eligible
  • Active seizure or history of seizure disorder

Locations & Contacts

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Temporarily closed to accrual
Contact: Vincent Chung
Phone: 800-826-4673
Email: becomingapatient@coh.org
Sacramento
University of California Davis Comprehensive Cancer Center
Status: Temporarily closed to accrual
Contact: Helen K. Chew
Phone: 916-734-3089
South Pasadena
City of Hope South Pasadena
Status: Temporarily closed to accrual
Contact: Stephen C. Koehler
Phone: 800-826-4673
Email: becomingapatient@coh.org

Florida

Tampa
Moffitt Cancer Center
Status: Temporarily closed to accrual
Contact: Amit Mahipal
Phone: 800-456-7121
Email: canceranswers@moffitt.org

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Temporarily closed to accrual
Contact: Suresh Sakkarai Ramalingam
Phone: 404-778-1868

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Temporarily closed to accrual
Contact: Michael Anthony Carducci
Phone: 410-955-8804
Email: jhcccro@jhmi.edu

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: Temporarily closed to accrual
Contact: Geoffrey Ira Shapiro
Phone: 877-442-3324

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Temporarily closed to accrual
Contact: Ulka N. Vaishampayan
Phone: 313-576-9790
Email: ctoadmin@karmanos.org

New Jersey

New Brunswick
Rutgers Cancer Institute of New Jersey
Status: Temporarily closed to accrual
Contact: Nancy Chan
Phone: 732-235-8675

New York

Bronx
Montefiore Medical Center - Moses Campus
Status: Active
Contact: Hussein Abdul-Hassan Tawbi
Phone: 412-647-8073
Montefiore Medical Center-Weiler Hospital
Status: Temporarily closed to accrual
Contact: Sanjay Goel
Phone: 718-379-6866
Email: aaraiza@montefiore.org
New York
Memorial Sloan Kettering Cancer Center
Status: Temporarily closed to accrual
Contact: David Michael Hyman
Phone: 212-639-7592

Ohio

Cleveland
Case Western Reserve University
Status: Temporarily closed to accrual
Contact: Afshin Dowlati
Phone: 800-641-2422
Email: CTUReferral@UHhospitals.org

Pennsylvania

Hershey
Penn State Milton S Hershey Medical Center
Status: Temporarily closed to accrual
Contact: Chandra P. Belani
Phone: 717-531-3779
Email: CTO@hmc.psu.edu
Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Temporarily closed to accrual
Contact: Hussein Abdul-Hassan Tawbi
Phone: 412-647-8073

Texas

Houston
M D Anderson Cancer Center
Status: Temporarily closed to accrual
Contact: Hussein Abdul-Hassan Tawbi
Phone: 877-312-3961

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Temporarily closed to accrual
Contact: Ticiana A. Leal
Phone: 800-622-8922

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the pharmacokinetics and pharmacodynamics of ABT-888 (veliparib) in patients with varying degrees of renal or hepatic dysfunction.

II. To determine the maximum tolerated dose (MTD) of ABT-888 in combination with carboplatin and paclitaxel for patients with varying degrees of liver or kidney dysfunction.

III. To provide dosing recommendations for ABT-888 in combination with carboplatin and paclitaxel based on degree of hepatic and renal impairment.

SECONDARY OBJECTIVES:

I. To define the dose-limiting toxicity (DLT) and other toxicities associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction.

II. To evaluate the pharmacokinetic parameters of ABT-888, carboplatin, and paclitaxel when administered as a combination in patients with varying degrees of renal or hepatic dysfunction.

III. To evaluate the pharmacodynamic measurement of poly-ADP-ribosylated (PAR) and platinum adducts in tumor cells associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction.

OUTLINE: This is a dose-escalation study of veliparib.

Patients receive veliparib* orally (PO) twice daily (BID) on days 1-7 and paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

NOTE: * All patients receive a single dose of veliparib PO on day -6 before course 1 (except patients with very severe renal dysfunction who receive veliparib on day -5 or -6 to coincide with a dialysis day).

After completion of study treatment, patients are followed up for 4 weeks.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
University of Pittsburgh Cancer Institute (UPCI)

Principal Investigator
Hussein Abdul-Hassan Tawbi

Trial IDs

Primary ID 8808
Secondary IDs NCI-2011-02500, UPCI 10-115, CDR0000700997, UPCI-10-115
Clinicaltrials.gov ID NCT01366144