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

This study is currently recruiting participants.
Verified December 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01366144
First received: June 2, 2011
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

This phase I trial studies 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.


Condition Intervention Phase
Extensive Stage Small Cell Lung Cancer
Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor
Recurrent Breast Cancer
Recurrent Melanoma
Recurrent Non-small Cell Lung Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Ovarian Germ Cell Tumor
Recurrent Small Cell Lung Cancer
Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor
Stage IV Breast Cancer
Stage IV Melanoma
Stage IV Non-small Cell Lung Cancer
Stage IV Ovarian Epithelial Cancer
Stage IV Ovarian Germ Cell Tumor
Unspecified Adult Solid Tumor, Protocol Specific
Drug: veliparib
Drug: paclitaxel
Drug: carboplatin
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD of veliparib in combination with carboplatin and paclitaxel using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to day 21 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics and pharmacodynamics of veliparib in patients with varying degrees of renal or hepatic dysfunction [ Time Frame: Day -6 and 3 (of course 1 after veliparib dosing) ] [ Designated as safety issue: No ]
    The effect of dysfunction on pharmacokinetics will be explored by comparing each pharmacokinetic parameter across all cohorts using one-way analysis (ANOVA) or Kruskal-Wallis test. The level of each protein will be compared between responders and non-responders using the Wilcoxon signed rank test.


Secondary Outcome Measures:
  • DLT and other toxicities as assessed by NCI CTCAE v4.0 [ Time Frame: Up to day 21 ] [ Designated as safety issue: Yes ]
  • Response and incidence of stable disease of patients with varying degrees of renal or hepatic dysfunction proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Responses and incidence of stable disease will be tabulated by disease diagnosis and by dose level. We will also report 95% confidence limits on the response rates.

  • Time to progression of patients with varying degrees of renal or hepatic dysfunction [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 276
Study Start Date: June 2011
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (veliparib, paclitaxel, carboplatin)

Patients receive veliparib* PO BID on days 1-7 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 3. Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Blood and hair follicle samples are collected at baseline, on days -5 or -6, and on day 3 of course 1 for pharmacokinetic and pharmacodynamic studies. Tumor tissue biopsies may also be collected at baseline and on day 3.

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).

Drug: veliparib
Given PO
Other Name: ABT-888
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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 of 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 multicenter, dose-escalation study of veliparib. Patients are stratified according to degree of renal dysfunction (normal vs moderate vs severe vs very severe) or hepatic dysfunction (mild vs mild with transaminase elevation vs moderately severe vs severe).

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. Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Blood and hair follicle samples are collected at baseline, on days -5 or -6, and on day 3 of course 1 for pharmacokinetic and pharmacodynamic studies. Tumor tissue biopsies may also be collected at baseline and on day 3.

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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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); or 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 (ANC) >= 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) AND 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01366144

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Vincent Chung    626-471-9200    VChung@coh.org   
Principal Investigator: Vincent Chung         
UC Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Helen K. Chew    916-734-3772    helen.chew@ucdmc.ucdavis.edu   
Principal Investigator: Helen K. Chew         
City of Hope- South Pasadena Cancer Center Recruiting
South Pasadena, California, United States, 91030
Contact: Stephen C. Koehler    626-396-2900    Skoehler@cohmg.com   
Principal Investigator: Stephen C. Koehler         
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Amit Mahipal    813-745-5717    amit.mahipal@moffitt.org   
Principal Investigator: Amit Mahipal         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Suresh S. Ramalingam    404-778-4381    suresh.ramalingam@emory.edu   
Principal Investigator: Suresh S. Ramalingam         
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287-8936
Contact: Michael A. Carducci       carducci@jhmi.edu   
Principal Investigator: Michael A. Carducci         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Geoffrey I. Shapiro    617-632-4942    geoffrey_shapiro@dfci.harvard.edu   
Principal Investigator: Geoffrey I. Shapiro         
United States, Michigan
Wayne State University Recruiting
Detroit, Michigan, United States, 48202
Contact: Patricia M. LoRusso    313-576-8716    lorussop@karmanos.org   
Principal Investigator: Patricia M. LoRusso         
United States, New York
Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Sanjay Goel    718-904-2900    sgoel@montefiore.org   
Principal Investigator: Sanjay Goel         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: David M. Hyman    646-888-4544    hymand@mskcc.org   
Principal Investigator: David M. Hyman         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: E. Claire Dees    919-843-7714    claire_dees@med.unc.edu   
Principal Investigator: E. Claire Dees         
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Afshin Dowlati    216-844-1228    axd44@case.edu   
Principal Investigator: Afshin Dowlati         
United States, Pennsylvania
Penn State Milton S Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Chandra P. Belani    717-531-1078    cbelani@psu.edu   
Principal Investigator: Chandra P. Belani         
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Hussein A. Tawbi    412-648-6466    tawbhx@upmc.edu   
Principal Investigator: Hussein A. Tawbi         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Daniel L. Mulkerin    608-265-9771    dm2@medicine.wisc.edu   
Principal Investigator: Daniel L. Mulkerin         
Sponsors and Collaborators
Investigators
Principal Investigator: Hussein Tawbi University of Pittsburgh
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01366144     History of Changes
Other Study ID Numbers: NCI-2011-02500, NCI-2011-02500, CDR0000700997, UPCI-10-115, UPCI 10-115, 8808, U01CA099168, U01CA070095, U01CA069856, U01CA062502, U01CA062505, P30CA047904
Study First Received: June 2, 2011
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Melanoma
Small Cell Lung Carcinoma
Neoplasms, Germ Cell and Embryonal
Germinoma
Ovarian Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Site
Breast Diseases
Skin Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms

ClinicalTrials.gov processed this record on April 20, 2014