Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00535119
First received: September 25, 2007
Last updated: July 28, 2014
Last verified: April 2014
  Purpose

This phase I trial is studying the side effects and best dose of veliparib when given together with carboplatin and paclitaxel in treating patients with advanced solid cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, 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 carboplatin and paclitaxel may help kill more tumor cells.


Condition Intervention Phase
BRCA1 Mutation Carrier
BRCA2 Mutation Carrier
Hereditary Breast/Ovarian Cancer (BRCA1, BRCA2)
Unspecified Adult Solid Tumor, Protocol Specific
Drug: veliparib
Drug: carboplatin
Drug: paclitaxel
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: A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Recommended phase II dose (RP2D) for each stratum [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
    The RP2D for each cohort will be defined by the study separately. Standard up & down dose-escalation scheme to determine the RP2D will be use, and toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.


Secondary Outcome Measures:
  • Toxicities as assessed by CTCAE v.4.0 [ Time Frame: From the time of their first treatment with veliparib to up to 4 weeks post-treatment ] [ Designated as safety issue: Yes ]
    Toxicities will be defined as regimen-related if they are possibly, probably or definitely related to treatment. 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. Serious (≥ Grade 3) toxicities will be described on a patient-by-patient basis and will include any relevant baseline data.

  • Dose-limiting toxicity (DLT) [ Time Frame: During course 1 ] [ Designated as safety issue: Yes ]
    Toxicities should be attributable to the study drug(s) to constitute DLT. Patients will be considered evaluable for DLT if they are eligible, and if they receive any amount of treatment and experience DLT or complete the first course of treatment

  • Responses to veliparib in combination with carboplatin and paclitaxel [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.

  • Incidence of stable disease (SD) [ Time Frame: Measured from the start of the treatment until the criteria for progression are met, assessed up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    SD is defined as neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started.

  • Time to progression (TTP) [ Time Frame: Time from start of treatment to time of progression, assessed up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Progression will be evaluated in this study using the new international criteria proposed by RECIST. TTP will be displayed for all patients and for patients who have responded; no formal statistical analysis is planned.

  • PAR levels [ Time Frame: Up to 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Changes will be summarized as means and standard deviations. A statistical test of the null hypothesis of no change in each variable will be done using the Wilcoxon signed-ranks procedure. Measurements of the two variables at additional time points will be analyzed in a descriptive fashion using tables and plots.

  • Frequency of platinum-DNA adducts [ Time Frame: At baseline and 4 weeks post-treatment ] [ Designated as safety issue: No ]
    Changes will be summarized as means and standard deviations. A statistical test of the null hypothesis of no change in each variable will be done using the Wilcoxon signed-ranks procedure. Measurements of the two variables at additional time points will be analyzed in a descriptive fashion using tables and plots.


Enrollment: 107
Study Start Date: September 2007
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy and chemotherapy)
Patients receive carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib PO twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: veliparib
Given PO
Other Name: ABT-888
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the recommended dose for phase II studies of veliparib (ABT-888 ) that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies. (Stratum I) II. To determine the recommended dose for phase II studies of veliparib that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies that harbor a germline BRCA1/2 mutation. (Stratum II) (added 04/07/09)

SECONDARY OBJECTIVES:

I. To define the dose-limiting toxicity and other toxicities associated with the use of this combination.

II. To obtain preliminary evidence of antitumor activity in patients treated with this combination.

III. To evaluate the pharmacokinetic parameters of veliparib, carboplatin, and paclitaxel when administered as a combination.

IV. To conduct correlative science studies.

OUTLINE: This is a multicenter, dose-escalation study of veliparib. Patients are stratified according to BRCA status (no [stratum I] vs yes [stratum II]).

Patients receive carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib orally (PO) twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo peripheral blood mononuclear cell collection periodically for pharmacokinetic and biomarker studies.

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:

  • Histologically or cytologically confirmed advanced solid malignancy
  • Patients enrolled in stratum II of the study must have BRCA1/2 mutation (added 04/07/09)
  • Patients with CNS metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for > 3 months and must be off steroid treatment prior to study enrollment
  • ECOG performance status 0-2
  • Life expectancy > 12 weeks
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
  • More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 3 weeks since prior radiotherapy
  • Prior veliparib allowed

Exclusion Criteria:

  • Known history of allergic reactions to veliparib, carboplatin, or Cremophor-paclitaxel
  • Uncontrolled intercurrent illness, including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
  • Psychiatric illness or social situations that would preclude compliance with study requirements
  • Peripheral neuropathy > grade 1
  • Inability to take oral medications on a continuous basis
  • Active seizure or history of seizure disorder
  • Evidence of bleeding diathesis
  • Received > 3 prior chemotherapy regimens for advanced stage disease for patients enrolled in stratum I (there is no upper limit on the number of prior regimens for patients enrolled in stratum II) (added 04/07/09)

    • Adjuvant chemotherapy administered ≥ 2 years prior to enrollment to the study does not count as a prior chemotherapy regimen
  • Other concurrent investigational agents
  • Concurrent combination antiretroviral therapy for HIV-positive patients
  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: NCT00535119

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
City of Hope
Duarte, California, United States, 91010
University of Southern California/Norris Cancer Center
Los Angeles, California, United States, 90033
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Pennsylvania
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Investigators
Principal Investigator: Suresh Ramalingam University of Pittsburgh
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00535119     History of Changes
Other Study ID Numbers: NCI-2009-00258, NCI-2009-00258, PCI-07-015, CDR0000566233, UPCI # 07-015, 7967, N01CM00038, P30CA047904, U01CA099168
Study First Received: September 25, 2007
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ovarian Neoplasms
Hereditary Breast and Ovarian Cancer Syndrome
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Breast Neoplasms
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Breast Diseases
Skin Diseases
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014