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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
BRCA1 Mutation Carrier, BRCA2 Mutation Carrier, Hereditary Breast/Ovarian Cancer (BRCA1, BRCA2), Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Recommended phase II dose (RP2D) for each stratum

Outcome Description:

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.

Outcome Time Frame:

Up to 4 weeks

Safety Issue:

Yes

Principal Investigator

Suresh Ramalingam

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Pittsburgh

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00258

NCT ID:

NCT00535119

Start Date:

September 2007

Completion Date:

Related Keywords:

  • brca1 Mutation Carrier
  • brca2 Mutation Carrier
  • Hereditary Breast/Ovarian Cancer (brca1, brca2)
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Ovarian Neoplasms

Name

Location
University of Pittsburgh Cancer Institute Pittsburgh, Pennsylvania  15213
City of Hope Medical Center Duarte, California  91010
City of Hope Duarte, California  91010
University of Pittsburgh Pittsburgh, Pennsylvania  15261
Emory University Atlanta, Georgia  30322
UC Davis Comprehensive Cancer Center Sacramento, California  95817
University of Southern California Los Angeles, California  90033
Penn State Milton S Hershey Medical Center Hershey, Pennsylvania  17033