Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

ABT-888, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Biomarker/Laboratory analysis, Treatment Active 18 and over NCI PCI-07-015 07-015, 7967, NCT00535119

Objectives

Primary

1. To determine the recommended dose for phase II studies of ABT-888 that can be administered in combination with carboplatin and paclitaxel in patients with advanced solid malignancies.

Secondary

1. To define the dose-limiting toxicity and other toxicities associated with the use of this combination.
2. To obtain preliminary evidence of antitumor activity in patients treated with this combination.
3. To evaluate the pharmacokinetic parameters of ABT-888, carboplatin, and paclitaxel when administered as a combination.
4. To conduct correlative science studies including determination of the effect of ABT-888 on carboplatin-induced DNA adduct formation in tumor specimens.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed advanced solid malignancy



• Patients with brain metastasis should have stable disease ≥ 4 weeks following therapy for brain metastasis (i.e., surgery, radiotherapy, stereotactic radiosurgery)

Prior/Concurrent Therapy:

Inclusion criteria:

• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 3 weeks since prior radiotherapy
• Prior ABT-888 allowed

Exclusion criteria:

• Received > 2 prior chemotherapy regimens
  • Adjuvant chemotherapy administered ≥ 2 years prior to enrollment to the study does not count as a prior chemotherapy regimen
• Other concurrent investigational agents
• Prior paclitaxel
• Concurrent anticoagulants for patients who undergo biopsy as part of the study in the expanded dose cohort
• Concurrent combination antiretroviral therapy for HIV-positive patients

Patient Characteristics:

Inclusion criteria:

• 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

Exclusion criteria:

• Known history of allergic reactions to ABT-888, 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
• History of seizure disorder
• Evidence of bleeding diathesis
• Preexisting coagulopathy in patients who undergo biopsy as part of the study in the expanded dose cohort

Expected Enrollment

Outcomes

Recommended phase II dose

Toxicity
Stable disease
Time to progression
Poly-ADP ribose (PAR) levels at baseline and after completion of study treatment
Frequency of platinum DNA adducts at baseline and after completion of study treatment
Pharmacokinetics

Outline

Patients receive escalating doses of oral ABT-888 twice daily on days 1-7 (beginning in course 2) in combination with carboplatin IV over 30 minutes and paclitaxel IV over 3 hours on day 3. Treatment repeats every 3 weeks for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Peripheral blood mononuclear cells are collected on day 1 of course 1 and days 1 and 3 of course 2 for pharmacokinetic studies, evaluation of DNA adducts, and Poly-ADP ribose (PAR) levels.

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

Trial Contact Information

Trial Lead Organizations

UPMC Cancer Centers

Suresh Ramalingam, MD, Protocol chair		Ph: 412-648-6619 Email: sar18@pitt.edu
Chandra Belani, MD, Protocol co-chair		Ph: 717-531-1078 Email: cbelani@hmc.psu.edu

U.S.A.
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Sacramento
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
Pennsylvania
	Pittsburgh
	UPMC Cancer Centers
		Clinical Trials Office - UPMC Cancer Centers	Ph:  412-647-8073

Registry Information
Official Title		A Phase I Study of ABT-888 in Combination with Carboplatin and Paclitaxel in Advanced Solid Malignancies
Trial Start Date		2007-07-01 (estimated)
Trial Completion Date		2007-11-28 (estimated)
Registered in ClinicalTrials.gov		NCT00535119
Date Submitted to PDQ		2007-09-06
Information Last Verified		2008-05-20
NCI Grant/Contract Number		CA99168, CA47904