CClinicalTrials.gg
Active, not recruitingNCT01366144Updated Sep 4, 2026

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

A Phase 1 interventional study of Carboplatin and Laboratory Biomarker Analysis in Breast Carcinoma, Carcinoma of Unknown Primary and Endometrial Carcinoma, sponsored by National Cancer Institute (NCI). Active, not recruiting at 17 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-04.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
94
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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 Solid Neoplasm
  • Ovarian Carcinoma
  • Renal Failure
  • Unresectable Malignant Neoplasm
  • Urothelial Carcinoma
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
94 participants (actual)

Study arms

  • 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 · Other: Laboratory Biomarker Analysis · Drug: Paclitaxel · Other: Pharmacological Study · Drug: Veliparib

Interventions

  • DrugCarboplatin

    Given IV

    Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • DrugPaclitaxel

    Given IV

    Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

  • OtherPharmacological Study

    Correlative studies

  • DrugVeliparib

    Given PO

    Also known as: ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Day -6 and 3 of course 1 after veliparib dosing

  2. 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 outcomes

  1. 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.

    Time frame: Up to 4 weeks after completion of study treatment

  2. 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.

    Time frame: Up to 4 weeks after completion of study treatment

  3. 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 frame: Up to 4 weeks after completion of study treatment

  4. Time to progression

    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 outcomes

  1. Change in PAR levels

    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

  2. Change in gamma-H2AX levels

    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

06

Study locations

17 sites
  • 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
  • UPMC Hillman Cancer Center
    Pittsburgh, Pennsylvania 15232, United States
  • UT MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • University of Wisconsin Carbone Cancer Center - University Hospital
    Madison, Wisconsin 53792, United States
07

Registry details

Key details

Study ID
NCT01366144
Lead sponsor
National Cancer Institute (NCI)
Collaborators
Abbott
Responsible party
Sponsor
First posted
Jun 3, 2011
Start date
Jun 20, 2011
Primary completion
Nov 10, 2017
Completion
Mar 3, 2027 (estimated)
Last update
Sep 4, 2026

Study contacts

Hussein A Tawbi
principal investigator · University of Pittsburgh Cancer Institute (UPCI)

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion