Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer

Adult Solid Neoplasm Clinical Trial

Official title:

A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00535119
• Other study ID #: NCI-2009-00258
• Secondary ID: NCI-2009-00258PC
• Status: Completed
• Phase: Phase 1
• First received: September 25, 2007
• Last updated: May 21, 2015
• Start date: September 2007

Study information

• Verified date: April 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase I trial is studying the side effects and best dose of veliparib when given together with carboplatin and paclitaxel in treating patients with advanced solid cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving veliparib together with carboplatin and paclitaxel may help kill more tumor cells.

Description:

PRIMARY OBJECTIVES:

I. To determine the recommended dose for phase II studies of veliparib (ABT-888 ) that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies. (Stratum I) II. To determine the recommended dose for phase II studies of veliparib that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies that harbor a germline BRCA1/2 mutation. (Stratum II) (added 04/07/09)

SECONDARY OBJECTIVES:

I. To define the dose-limiting toxicity and other toxicities associated with the use of this combination.

II. To obtain preliminary evidence of antitumor activity in patients treated with this combination.

III. To evaluate the pharmacokinetic parameters of veliparib, carboplatin, and paclitaxel when administered as a combination.

IV. To conduct correlative science studies.

OUTLINE: This is a multicenter, dose-escalation study of veliparib. Patients are stratified according to BRCA status (no [stratum I] vs yes [stratum II]).

Patients receive carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 3 hours on day 3 and veliparib orally (PO) twice daily on days 1-7 until the recommended phase II dose is determined. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo peripheral blood mononuclear cell collection periodically for pharmacokinetic and biomarker studies.

After completion of study treatment, patients are followed up for 4 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed advanced solid malignancy

• Patients enrolled in stratum II of the study must have BRCA1/2 mutation (added 04/07/09)

• Patients with CNS metastases must be stable after therapy for CNS metastases (such as surgery, radiotherapy or stereotactic radiosurgery) for > 3 months and must be off steroid treatment prior to study enrollment

• ECOG performance status 0-2

• Life expectancy > 12 weeks

• ANC = 1,500/µL

• Platelet count = 100,000/µL

• Total bilirubin = 1.5 times upper limit of normal (ULN)

• AST and ALT = 2.5 times ULN

• Creatinine normal OR creatinine clearance = 60 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for = 3 months after completion of study treatment

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)

• More than 3 weeks since prior radiotherapy

• Prior veliparib allowed

Exclusion Criteria:

• Known history of allergic reactions to veliparib, carboplatin, or Cremophor-paclitaxel

• Uncontrolled intercurrent illness, including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situations that would preclude compliance with study requirements

• Peripheral neuropathy > grade 1

• Inability to take oral medications on a continuous basis

• Active seizure or history of seizure disorder

• Evidence of bleeding diathesis

• Received > 3 prior chemotherapy regimens for advanced stage disease for patients enrolled in stratum I (there is no upper limit on the number of prior regimens for patients enrolled in stratum II) (added 04/07/09)

• Adjuvant chemotherapy administered = 2 years prior to enrollment to the study does not count as a prior chemotherapy regimen

• Other concurrent investigational agents

• Concurrent combination antiretroviral therapy for HIV-positive patients

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Solid Neoplasm
• BRCA1 Mutation Carrier
• BRCA2 Mutation Carrier
• Hereditary Breast and Ovarian Cancer Syndrome

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/Winship Cancer Institute	Atlanta	Georgia
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended phase II dose (RP2D) for each stratum	The RP2D for each cohort will be defined by the study separately. Standard up & down dose-escalation scheme to determine the RP2D will be use, and toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.	Up to 4 weeks	Yes
Secondary	Dose-limiting toxicity (DLT)	Toxicities should be attributable to the study drug(s) to constitute DLT. Patients will be considered evaluable for DLT if they are eligible, and if they receive any amount of treatment and experience DLT or complete the first course of treatment	During course 1	Yes
Secondary	Frequency of platinum-DNA adducts	Changes will be summarized as means and standard deviations. A statistical test of the null hypothesis of no change in each variable will be done using the Wilcoxon signed-ranks procedure. Measurements of the two variables at additional time points will be analyzed in a descriptive fashion using tables and plots.	At baseline and 4 weeks post-treatment	No
Secondary	Incidence of stable disease (SD)	SD is defined as neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started.	Measured from the start of the treatment until the criteria for progression are met, assessed up to 4 weeks post-treatment	No
Secondary	PAR levels	Changes will be summarized as means and standard deviations. A statistical test of the null hypothesis of no change in each variable will be done using the Wilcoxon signed-ranks procedure. Measurements of the two variables at additional time points will be analyzed in a descriptive fashion using tables and plots.	Up to 4 weeks post-treatment	No
Secondary	Responses to veliparib in combination with carboplatin and paclitaxel	Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.	Up to 4 weeks post-treatment	No
Secondary	Time to progression (TTP)	Progression will be evaluated in this study using the new international criteria proposed by RECIST. TTP will be displayed for all patients and for patients who have responded; no formal statistical analysis is planned.	Time from start of treatment to time of progression, assessed up to 4 weeks post-treatment	No
Secondary	Toxicities as assessed by CTCAE v.4.0	Toxicities will be defined as regimen-related if they are possibly, probably or definitely related to 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. Serious (= Grade 3) toxicities will be described on a patient-by-patient basis and will include any relevant baseline data.	From the time of their first treatment with veliparib to up to 4 weeks post-treatment	Yes