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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

Primary Purpose

Breast Carcinoma, Carcinoma of Unknown Primary, Endometrial Carcinoma

Status
Active
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 Breast Carcinoma

Eligibility Criteria

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

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

Sites / Locations

  • City of Hope Comprehensive Cancer Center
  • University of California Davis Comprehensive Cancer Center
  • City of Hope South Pasadena
  • Moffitt Cancer Center
  • Emory University Hospital/Winship Cancer Institute
  • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Dana-Farber Cancer Institute
  • Wayne State University/Karmanos Cancer Institute
  • Rutgers Cancer Institute of New Jersey
  • Montefiore Medical Center-Weiler Hospital
  • Montefiore Medical Center - Moses Campus
  • Memorial Sloan Kettering Cancer Center
  • Case Western Reserve University
  • Penn State Milton S Hershey Medical Center
  • University of Pittsburgh Cancer Institute (UPCI)
  • M D Anderson Cancer Center
  • University of Wisconsin Carbone Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (veliparib, paclitaxel, carboplatin)

Arm Description

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).

Outcomes

Primary Outcome Measures

PK parameters of veliparib
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.
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

Secondary Outcome Measures

Incidence of toxicities as assessed by NCI CTCAE v4.0
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
Responses will be tabulated by disease diagnosis and by dose level. 95% confidence limits will also be reported on the response rates.
Incidence of stable disease as assessed by RECIST version 1.1
Incidence of stable disease will be tabulated by disease diagnosis and by dose level.
Time to progression
Displayed for all patients and for patients who have responded; no formal statistical analysis is planned.

Full Information

First Posted
June 2, 2011
Last Updated
October 19, 2023
Sponsor
National Cancer Institute (NCI)
Collaborators
Abbott
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1. Study Identification

Unique Protocol Identification Number
NCT01366144
Brief Title
Veliparib, Paclitaxel, and Carboplatin in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery and Liver or Kidney Dysfunction
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 Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 20, 2011 (Actual)
Primary Completion Date
November 10, 2017 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Carcinoma, Carcinoma of Unknown Primary, Endometrial Carcinoma, Esophageal Carcinoma, Liver Failure, Lung Carcinoma, Malignant Head and Neck Neoplasm, Malignant Testicular Neoplasm, Melanoma, Metastatic Malignant Neoplasm, Ovarian Carcinoma, Renal Failure, Unresectable Malignant Neoplasm, Urothelial Carcinoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Treatment (veliparib, paclitaxel, carboplatin)
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, 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
PK parameters of veliparib
Description
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.
Time Frame
Day -6 and 3 of course 1 after veliparib dosing
Title
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
Secondary Outcome Measure Information:
Title
Incidence of toxicities as assessed by NCI CTCAE v4.0
Description
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.
Time Frame
Up to 4 weeks after completion of study treatment
Title
Response rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Description
Responses will be tabulated by disease diagnosis and by dose level. 95% confidence limits will also be reported on the response rates.
Time Frame
Up to 4 weeks after completion of study treatment
Title
Incidence of stable disease as assessed by RECIST version 1.1
Description
Incidence of stable disease will be tabulated by disease diagnosis and by dose level.
Time Frame
Up to 4 weeks after completion of study treatment
Title
Time to progression
Description
Displayed for all patients and for patients who have responded; no formal statistical analysis is planned.
Time Frame
Up to 4 weeks after completion of study treatment
Other Pre-specified Outcome Measures:
Title
Change in PAR levels
Description
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.
Time Frame
Baseline to up to 4 weeks
Title
Change in gamma-H2AX levels
Description
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.
Time Frame
Baseline to up to 4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hussein A Tawbi
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
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
City of Hope South Pasadena
City
South Pasadena
State/Province
California
ZIP/Postal Code
91030
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Johns Hopkins University/Sidney Kimmel Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Montefiore Medical Center-Weiler Hospital
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Montefiore Medical Center - Moses Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Case Western Reserve University
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
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
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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