Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01366144
Other study ID # NCI-2011-02500
Secondary ID NCI-2011-02500CD
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date June 20, 2011
Est. completion date March 5, 2025

Study information

Verified date March 2024
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 94
Est. completion date March 5, 2025
Est. primary completion date November 10, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms

  • Breast Carcinoma
  • Breast Neoplasms
  • Carcinoma
  • Carcinoma of Unknown Primary
  • Endometrial Carcinoma
  • Endometrial Neoplasms
  • Esophageal Carcinoma
  • Esophageal Neoplasms
  • Head and Neck Neoplasms
  • Liver Failure
  • Lung Carcinoma
  • Malignant Head and Neck Neoplasm
  • Malignant Testicular Neoplasm
  • Melanoma
  • Metastatic Malignant Neoplasm
  • Neoplasms
  • Ovarian Carcinoma
  • Renal Failure
  • Testicular Neoplasms
  • Unresectable Malignant Neoplasm
  • Urothelial Carcinoma

Intervention

Drug:
Carboplatin
Given IV
Other:
Laboratory Biomarker Analysis
Correlative studies
Drug:
Paclitaxel
Given IV
Other:
Pharmacological Study
Correlative studies
Drug:
Veliparib
Given PO

Locations

Country Name City State
United States Emory University Hospital/Winship Cancer Institute Atlanta Georgia
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Montefiore Medical Center - Moses Campus Bronx New York
United States Montefiore Medical Center-Weiler Hospital Bronx New York
United States Case Western Reserve University Cleveland Ohio
United States Wayne State University/Karmanos Cancer Institute Detroit Michigan
United States City of Hope Comprehensive Cancer Center Duarte California
United States Penn State Milton S Hershey Medical Center Hershey Pennsylvania
United States M D Anderson Cancer Center Houston Texas
United States University of Wisconsin Carbone Cancer Center - University Hospital Madison Wisconsin
United States Rutgers Cancer Institute of New Jersey New Brunswick New Jersey
United States Memorial Sloan Kettering Cancer Center New York New York
United States University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States City of Hope South Pasadena South Pasadena California
United States Moffitt Cancer Center Tampa Florida

Sponsors (2)

Lead Sponsor Collaborator
National Cancer Institute (NCI) Abbott

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other 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. Baseline to up to 4 weeks
Other 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. Baseline to up to 4 weeks
Primary 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
Primary 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 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. Up to 4 weeks after completion of study treatment
Secondary 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. Up to 4 weeks after completion of study treatment
Secondary 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. Up to 4 weeks after completion of study treatment
Secondary Time to progression Displayed for all patients and for patients who have responded; no formal statistical analysis is planned. Up to 4 weeks after completion of study treatment
See also
  Status Clinical Trial Phase
Recruiting NCT05094804 - A Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents Phase 1/Phase 2
Completed NCT03979872 - Risk Information and Skin-cancer Education for Undergraduate Prevention N/A
Recruiting NCT04986748 - Using QPOP to Predict Treatment for Sarcomas and Melanomas
Enrolling by invitation NCT00068003 - Harvesting Cells for Experimental Cancer Treatments
Recruiting NCT05707286 - Pilot Study to Determine Pro-Inflammatory Cytokine Kinetics During Immune Checkpoint Inhibitor Therapy
Active, not recruiting NCT05470283 - Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma Phase 1
Recruiting NCT05077137 - A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy Phase 1
Active, not recruiting NCT02721459 - XL888 + Vemurafenib + Cobimetinib for Unresectable BRAF Mutated Stage III/IV Melanoma Phase 1
Completed NCT00341939 - Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
Recruiting NCT05839912 - Excision of Lymph Node Trial (EXCILYNT) (Mel69) N/A
Recruiting NCT04971499 - A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma Phase 1/Phase 2
Recruiting NCT05263453 - HL-085+Vemurafenib to Treat Advanced Melanoma Patients With BRAF V600E/K Mutation Phase 2
Active, not recruiting NCT05060432 - Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors Phase 1/Phase 2
Not yet recruiting NCT06413680 - A First-In Human (FIH) Trial to Find Out if REGN10597 is Safe and How Well it Works for Adult Participants With Advanced Solid Organ Malignancies Phase 1/Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT03348891 - TNF in Melanoma Patients Treated With Immunotherapy N/A
Completed NCT03171064 - Exercise as a Supportive Measure for Patients Undergoing Checkpoint-inhibitor Treatment Phase 2
Not yet recruiting NCT05539118 - Interferon-α1b Combined With Toripalimab and Anlotinib Hydrochloride in Advanced Unresectable Melanoma Phase 1/Phase 2
Recruiting NCT05171374 - pRospective Evaluation of Clinical Outcomes in Patients With metAsTatIс melanOma Treated With dabrafeNib and trAmetinib in reaL practicE
Withdrawn NCT02854488 - Yervoy Pregnancy Surveillance Study