Breast Cancer Clinical Trial

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

Summary

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.

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Full Description

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.

View Eligibility Criteria

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

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

94

Study ID:

NCT01366144

Recruitment Status:

Active, not recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 17 Locations for this study

See Locations Near You

City of Hope Comprehensive Cancer Center
Duarte California, 91010, United States
University of California Davis Comprehensive Cancer Center
Sacramento California, 95817, United States
City of Hope South Pasadena
South Pasadena California, 91030, United States
Moffitt Cancer Center
Tampa Florida, 33612, United States
Emory University Hospital/Winship Cancer Institute
Atlanta Georgia, 30322, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit Michigan, 48201, United States
Rutgers Cancer Institute of New Jersey
New Brunswick New Jersey, 08903, United States
Montefiore Medical Center-Weiler Hospital
Bronx New York, 10461, United States
Montefiore Medical Center - Moses Campus
Bronx New York, 10467, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States
Case Western Reserve University
Cleveland Ohio, 44106, United States
Penn State Milton S Hershey Medical Center
Hershey Pennsylvania, 17033, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston Texas, 77030, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison Wisconsin, 53792, United States

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

94

Study ID:

NCT01366144

Recruitment Status:

Active, not recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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