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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| ClinicalTrials.gov Identifier: NCT01366144 |
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Recruitment Status :
Active, not recruiting
First Posted : June 3, 2011
Last Update Posted : June 1, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Drug: Carboplatin Other: Laboratory Biomarker Analysis Drug: Paclitaxel Other: Pharmacological Study Drug: Veliparib | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 94 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | June 20, 2011 |
| Actual Primary Completion Date : | November 10, 2017 |
| Arm | Intervention/treatment |
|---|---|
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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
Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Paclitaxel Given IV
Other Names:
Other: Pharmacological Study Correlative studies Drug: Veliparib Given PO
Other Names:
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- PK parameters of veliparib [ Time Frame: Day -6 and 3 of course 1 after veliparib dosing ]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 [ Time Frame: 21 days ]
- Incidence of toxicities as assessed by NCI CTCAE v4.0 [ Time Frame: Up to 4 weeks after completion of study 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. 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 [ Time Frame: Up to 4 weeks after completion of study treatment ]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 [ Time Frame: Up to 4 weeks after completion of study treatment ]Incidence of stable disease will be tabulated by disease diagnosis and by dose level.
- Time to progression [ Time Frame: Up to 4 weeks after completion of study treatment ]Displayed for all patients and for patients who have responded; no formal statistical analysis is planned.
- Change in PAR levels [ Time Frame: Baseline to up to 4 weeks ]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.
- Change in gamma-H2AX levels [ Time Frame: Baseline to up to 4 weeks ]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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | 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:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01366144
Show 17 study locations
| Principal Investigator: | Hussein A Tawbi | University of Pittsburgh Cancer Institute (UPCI) |
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Carcinoma Neoplasms Breast Neoplasms Endometrial Neoplasms Head and Neck Neoplasms Esophageal Neoplasms Testicular Neoplasms Liver Failure Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms by Site Breast Diseases Skin Diseases Hepatic Insufficiency Liver Diseases |
Digestive System Diseases Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Uterine Diseases Endocrine Gland Neoplasms Endocrine System Diseases Gonadal Disorders Gastrointestinal Neoplasms Digestive System Neoplasms Esophageal Diseases Gastrointestinal Diseases Genital Neoplasms, Male Testicular Diseases Paclitaxel |