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

Primary Purpose

Adult Solid Neoplasm, BRCA1 Mutation Carrier, BRCA2 Mutation Carrier

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carboplatin
Laboratory Biomarker Analysis
Paclitaxel
Pharmacological Study
Veliparib
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Solid Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Comprehensive Cancer Center
  • USC / Norris Comprehensive Cancer Center
  • University of California Davis Comprehensive Cancer Center
  • Emory University/Winship Cancer Institute
  • Penn State Milton S Hershey Medical Center
  • University of Pittsburgh Cancer Institute (UPCI)
  • University of Pittsburgh Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (enzyme inhibitor therapy and chemotherapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

Recommended phase II dose (RP2D) for each stratum
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

Dose-limiting toxicity (DLT)
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
Frequency of platinum-DNA adducts
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.
Incidence of stable disease (SD)
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.
PAR levels
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.
Responses to veliparib in combination with carboplatin and paclitaxel
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.
Time to progression (TTP)
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.
Toxicities as assessed by CTCAE v.4.0
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.

Full Information

First Posted
September 25, 2007
Last Updated
May 21, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00535119
Brief Title
Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
Official Title
A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Solid Neoplasm, BRCA1 Mutation Carrier, BRCA2 Mutation Carrier, Hereditary Breast and Ovarian Cancer Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
107 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (enzyme inhibitor therapy and chemotherapy)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplat, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Veliparib
Other Intervention Name(s)
ABT-888, PARP-1 inhibitor ABT-888
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Recommended phase II dose (RP2D) for each stratum
Description
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.
Time Frame
Up to 4 weeks
Secondary Outcome Measure Information:
Title
Dose-limiting toxicity (DLT)
Description
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
Time Frame
During course 1
Title
Frequency of platinum-DNA adducts
Description
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.
Time Frame
At baseline and 4 weeks post-treatment
Title
Incidence of stable disease (SD)
Description
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 Frame
Measured from the start of the treatment until the criteria for progression are met, assessed up to 4 weeks post-treatment
Title
PAR levels
Description
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.
Time Frame
Up to 4 weeks post-treatment
Title
Responses to veliparib in combination with carboplatin and paclitaxel
Description
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.
Time Frame
Up to 4 weeks post-treatment
Title
Time to progression (TTP)
Description
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.
Time Frame
Time from start of treatment to time of progression, assessed up to 4 weeks post-treatment
Title
Toxicities as assessed by CTCAE v.4.0
Description
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.
Time Frame
From the time of their first treatment with veliparib to up to 4 weeks post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suresh Ramalingam
Organizational Affiliation
University of Pittsburgh Cancer Institute (UPCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Emory University/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Penn State Milton S Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033-0850
Country
United States
Facility Name
University of Pittsburgh Cancer Institute (UPCI)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States

12. IPD Sharing Statement

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

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