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

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Adult Solid Neoplasm; Bladder Carcinoma; Breast Carcinoma; Endometrial Carcinoma; Esophageal Carcinoma; Lung Carcinoma; Malignant Head and Neck Neoplasm; Melanoma; Ovarian Neoplasm; Renal Pelvis and Ureter Urothelial Carcinoma; Testicular Lymphoma; Ureter Carcinoma; Urethral Carcinoma

Intervention: Carboplatin (Drug); Laboratory Biomarker Analysis (Other); Paclitaxel (Drug); Pharmacological Study (Other); Veliparib (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Hussein Tawbi, Principal Investigator, Affiliation: University of Pittsburgh Cancer Institute (UPCI)


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 or by stopping them from dividing. Giving veliparib together with paclitaxel and carboplatin may kill more tumor cells.

Clinical Details

Official title: An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

MTD of veliparib in combination with carboplatin and paclitaxel, determined according to incidence of DLT as graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0

PK parameters of veliparib

Secondary outcome:

Incidence of stable disease as assessed by RECIST version 1.1

Incidence of toxicities as assessed by NCI CTCAE v4.0

Response rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Time to progression

Detailed 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 therapy, patients are followed up for 4 weeks.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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 and Contacts

City of Hope Comprehensive Cancer Center, Duarte, California 91010, United States; Recruiting
Vincent Chung, Phone: 626-471-9200, Email: VChung@coh.org
Vincent Chung, Principal Investigator

University of California Davis Comprehensive Cancer Center, Sacramento, California 95817, United States; Recruiting
Helen K. Chew, Phone: 916-734-3772, Email: helen.chew@ucdmc.ucdavis.edu
Helen K. Chew, Principal Investigator

City of Hope South Pasadena, South Pasadena, California 91030, United States; Recruiting
Stephen C. Koehler, Phone: 626-396-2900, Email: Skoehler@cohmg.com
Stephen C. Koehler, Principal Investigator

Moffitt Cancer Center, Tampa, Florida 33612, United States; Recruiting
Amit Mahipal, Phone: 813-745-5717, Email: amit.mahipal@moffitt.org
Amit Mahipal, Principal Investigator

Emory University/Winship Cancer Institute, Atlanta, Georgia 30322, United States; Recruiting
Suresh S. Ramalingam, Phone: 404-778-4381, Email: suresh.ramalingam@emory.edu
Suresh S. Ramalingam, Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, Maryland 21287, United States; Recruiting
Michael A. Carducci, Phone: 410-614-6321, Email: carducci@jhmi.edu
Michael A. Carducci, Principal Investigator

Dana-Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Geoffrey I. Shapiro, Phone: 617-632-4942, Email: geoffrey_shapiro@dfci.harvard.edu
Geoffrey I. Shapiro, Principal Investigator

Wayne State University/Karmanos Cancer Institute, Detroit, Michigan 48201, United States; Recruiting
Ulka N. Vaishampayan, Phone: 313-576-8718, Email: vaishamu@karmanos.org
Ulka N. Vaishampayan, Principal Investigator

Albert Einstein College of Medicine, Bronx, New York 10461, United States; Recruiting
Sanjay Goel, Phone: 718-904-2900, Email: sgoel@montefiore.org
Sanjay Goel, Principal Investigator

Montefiore Medical Center - Moses Campus, Bronx, New York 10467-2490, United States; Recruiting
Hussein A. Tawbi, Phone: 412-692-2608, Email: tawbih@upmc.edu
Hussein A. Tawbi, Principal Investigator

Memorial Sloan-Kettering Cancer Center, New York, New York 10065, United States; Recruiting
David M. Hyman, Phone: 646-888-4544, Email: hymand@mskcc.org
David M. Hyman, Principal Investigator

University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States; Recruiting
Elizabeth C. Dees, Phone: 919-843-7714, Email: claire_dees@med.unc.edu
Elizabeth C. Dees, Principal Investigator

Case Western Reserve University, Cleveland, Ohio 44106, United States; Recruiting
Afshin Dowlati, Phone: 216-844-1228, Email: axd44@case.edu
Afshin Dowlati, Principal Investigator

Penn State Milton S Hershey Medical Center, Hershey, Pennsylvania 17033-0850, United States; Recruiting
Chandra P. Belani, Phone: 717-531-1078, Email: cbelani@psu.edu
Chandra P. Belani, Principal Investigator

University of Pittsburgh Cancer Institute (UPCI), Pittsburgh, Pennsylvania 15232, United States; Recruiting
Hussein A. Tawbi, Phone: 412-623-3483, Email: tawbih@upmc.edu
Hussein A. Tawbi, Principal Investigator

University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, United States; Recruiting
Ticiana B. Leal, Phone: 608-263-6222, Email: tbleal@medicine.wisc.edu
Ticiana B. Leal, Principal Investigator

Additional Information

Starting date: June 2011
Last updated: May 6, 2015

Page last updated: August 23, 2015

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