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. (see Contacts and Locations)
Verified February 2016 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: March 11, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Bladder Carcinoma
Breast Carcinoma
Carcinoma of Unknown Primary Origin
Endometrial Carcinoma
Esophageal Carcinoma
Lung Carcinoma
Malignant Head and Neck Neoplasm
Melanoma
Ovarian Neoplasm
Renal Pelvis and Ureter Urothelial Carcinoma
Testicular Lymphoma
Urethral Carcinoma
Drug: Carboplatin
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel
Other: Pharmacological Study
Drug: Veliparib
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, 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 [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • PK parameters of veliparib [ Time Frame: Day -6 and 3 of course 1 after veliparib dosing ] [ Designated as safety issue: No ]
    Standard quantitative and graphical statistical summaries of the derived PK parameters (e.g. area under curve and clearance) will be produced for each organ function cohort. The effect of dysfunction on pharmacokinetics will be explored by comparing each pharmacokinetic parameter across all cohorts using one-way analysis (analysis of variance) 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:
  • Incidence of stable disease as assessed by RECIST version 1.1 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Incidence of stable disease will be tabulated by disease diagnosis and by dose level.

  • Incidence of toxicities as assessed by NCI CTCAE v4.0 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: Yes ]
    The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category, grade and dose level. Severe and life-threatening toxicities and adverse event-related deaths (>= grade 3) will be described on a patient-by-patient basis and will include any relevant baseline data.

  • Response rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Responses will be tabulated by disease diagnosis and by dose level. 95% confidence limits will also be reported on the response rates.

  • Time to progression [ Time Frame: Up to 4 weeks after completion of study treatment ] [ Designated as safety issue: No ]
    Displayed for all patients and for patients who have responded; no formal statistical analysis is planned.


Other Outcome Measures:
  • Change in gamma-H2AX levels [ Time Frame: Baseline to up to 4 weeks ] [ Designated as safety issue: No ]
    Descriptive statistics (mean, standard deviation, median, range) for measurements of gamma-H2AX levels will provided with 95% CIs. When sample size permits, a formal statistical test using the Wilcoxon signed rank test will be used to compare the post treatment PAR levels to the baseline levels. When feasible, the level will be compared between responders and non-responders using the Wilcoxon signed rank test.

  • Change in PAR levels [ Time Frame: Baseline to up to 4 weeks ] [ Designated as safety issue: No ]
    Descriptive statistics (mean, standard deviation, median, range) for measurements of PAR levels will provided with 95% confidence intervals (CIs). When sample size permits, a formal statistical test using the Wilcoxon signed rank test will be used to compare the post treatment PAR levels to the baseline levels. When feasible, the level will be compared between responders and non-responders using the Wilcoxon signed rank test.


Estimated Enrollment: 276
Study Start Date: June 2011
Estimated Primary Completion Date: July 2017 (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.

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: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Other: Pharmacological Study
Correlative studies
Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888

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 treatment, patients are followed up for 4 weeks.

  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); 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
  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: NCT01366144

Locations
United States, California
City of Hope Comprehensive Cancer Center Active, not recruiting
Duarte, California, United States, 91010
University of California 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 Active, not recruiting
South Pasadena, California, United States, 91030
United States, Florida
Moffitt Cancer Center Terminated
Tampa, Florida, United States, 33612
United States, Georgia
Emory University/Winship Cancer Institute Terminated
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Michael A. Carducci    410-614-6321    carducci@jhmi.edu   
Principal Investigator: Michael A. Carducci         
United States, Massachusetts
Dana-Farber/Harvard Cancer Center 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/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Ulka N. Vaishampayan    313-576-8718    vaishamu@karmanos.org   
Principal Investigator: Ulka N. Vaishampayan         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Nancy Chan    732-235-8991    nancy.chan@cinj.rutgers.edu   
Principal Investigator: Nancy Chan         
United States, New York
Montefiore Medical Center - Moses Campus Recruiting
Bronx, New York, United States, 10467-2490
Contact: Hussein A. Tawbi    713-792-6111    HTawbi@mdanderson.org   
Principal Investigator: Hussein A. Tawbi         
Montefiore Medical Center-Weiler Hospital 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 Active, not recruiting
New York, New York, United States, 10065
United States, Ohio
Case Western Reserve University Active, not recruiting
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Penn State Hershey Cancer Institute-Clinical Trials Office Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Chandra P. Belani    717-531-5471    sgravino@hmc.psu.edu   
Principal Investigator: Chandra P. Belani         
University of Pittsburgh Cancer Institute (UPCI) Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: James Lee    412-623-2943    phase1@upmc.edu   
Principal Investigator: James Lee         
United States, Texas
University of Texas MD Anderson Cancer Center LAO Recruiting
Houston, Texas, United States, 77030
Contact: Hussein A. Tawbi    713-792-6111    HTawbi@mdanderson.org   
Principal Investigator: Hussein A. Tawbi         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Ticiana B. Leal    608-263-6222    tbleal@medicine.wisc.edu   
Principal Investigator: Ticiana B. Leal         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: James Lee University of Pittsburgh Cancer Institute (UPCI)
  More Information

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  P30CA047904  U01CA062490  U01CA062502  U01CA062505  U01CA069856  U01CA070095  U01CA099168  UM1CA186690  UM1CA186691  UM1CA186709  UM1CA186717 
Study First Received: June 2, 2011
Last Updated: March 11, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Endometrial Neoplasms
Esophageal Neoplasms
Head and Neck Neoplasms
Kidney Neoplasms
Lung Neoplasms
Neoplasms
Neoplasms, Unknown Primary
Ovarian Neoplasms
Ureteral Neoplasms
Urinary Bladder Neoplasms
Adnexal Diseases
Breast Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Kidney Diseases
Lung Diseases
Neoplasm Metastasis
Neoplasms by Histologic Type
Neoplasms by Site

ClinicalTrials.gov processed this record on May 02, 2016