Veliparib, Paclitaxel, and Carboplatin in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery and Liver or Kidney Dysfunction
An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors
18 other identifiers
interventional
94
1 country
17
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2011
Longer than P75 for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 2, 2011
CompletedFirst Posted
Study publicly available on registry
June 3, 2011
CompletedStudy Start
First participant enrolled
June 20, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 10, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
March 3, 2027
ExpectedApril 13, 2026
March 1, 2026
6.4 years
June 2, 2011
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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.
Day -6 and 3 of course 1 after veliparib dosing
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
21 days
Secondary Outcomes (4)
Incidence of toxicities as assessed by NCI CTCAE v4.0
Up to 4 weeks after completion of study treatment
Response rate as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Up to 4 weeks after completion of study treatment
Incidence of stable disease as assessed by RECIST version 1.1
Up to 4 weeks after completion of study treatment
Time to progression
Up to 4 weeks after completion of study treatment
Other Outcomes (2)
Change in PAR levels
Baseline to up to 4 weeks
Change in gamma-H2AX levels
Baseline to up to 4 weeks
Study Arms (1)
Treatment (veliparib, paclitaxel, carboplatin)
EXPERIMENTALPatients 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).
Interventions
Given IV
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)lead
- Abbottcollaborator
Study Sites (17)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
City of Hope South Pasadena
South Pasadena, California, 91030, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Hussein A Tawbi
University of Pittsburgh Cancer Institute (UPCI)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 2, 2011
First Posted
June 3, 2011
Study Start
June 20, 2011
Primary Completion
November 10, 2017
Study Completion (Estimated)
March 3, 2027
Last Updated
April 13, 2026
Record last verified: 2026-03