Clinical trial NCT00535119: Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
Official title: A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adult Solid Neoplasm
BRCA1 Mutation Carrier
BRCA2 Mutation Carrier
Hereditary Breast and Ovarian Cancer Syndrome
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-09-26
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Recommended phase II dose (RP2D) for each stratum
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: During course 1
measure: Frequency of platinum-DNA adducts
timeFrame: At baseline and 4 weeks post-treatment
measure: Incidence of stable disease (SD)
timeFrame: Measured from the start of the treatment until the criteria for progression are met, assessed up to 4 weeks post-treatment
measure: PAR levels
timeFrame: Up to 4 weeks post-treatment
measure: Responses to veliparib in combination with carboplatin and paclitaxel
timeFrame: Up to 4 weeks post-treatment
measure: Time to progression (TTP)
timeFrame: Time from start of treatment to time of progression, assessed up to 4 weeks post-treatment
measure: Toxicities as assessed by CTCAE v.4.0
timeFrame: From the time of their first treatment with veliparib to up to 4 weeks post-treatment
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Atlanta
country: United States
facility: Emory University/Winship Cancer Institute
state: Georgia
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute (UPCI)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh Cancer Institute (UPCI)
name: Suresh Ramalingam
role: PRINCIPAL_INVESTIGATOR
References: