Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This phase I trial is studying the side effects and best dose of veliparib in treating patients with malignant solid tumors that did not respond to previous therapy. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Further Study Information

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of chronically dosed single-agent ABT-888 (veliparib) in patients with either a refractory BRCA 1/2- mutated solid cancer; platinum- refractory ovarian, fallopian tube, or primary peritoneal cancer; or basal-like breast cancer.

SECONDARY OBJECTIVES:

I. To establish the safety and tolerability of single-agent ABT-888 in the above patient population. A dose expansion at the recommended phase II dose will be performed in 6-12 patients with germline BRCA mutations.

II. To determine the effects of ABT-888 treatment on the level of PARP inhibition and DNA damage in PBMCs and tumor samples or cells in malignant ascitic fluid III. To determine the pharmacokinetics (PK) of chronically dosed ABT-888. IV. To document any evidence of anti-tumor response.

OUTLINE: This is a multicenter study.

Patients receive veliparib* orally (PO) daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients receive veliparib once on day 1 of course 1 for pharmacokinetic and pharmacodynamic studies.

Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies. Samples are analyzed for plasma concentrations of veliparib by LC-MS; PARP inhibition levels; and γ-H2AX. Skin and hair samples may also be collected.

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

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed malignant solid tumor meeting ≥ 1 of the following criteria:

• Documented BRCA1/2 mutation AND a BRCA-related malignancy (e.g., primarily breast or ovarian cancer, but may include prostate or pancreatic cancer)

• Platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer

• Platinum-refractory is defined as progression or recurrence within 6 months of initial platinum response

• No platinum-resistant disease, defined as no prior response to platinum-based therapy (i.e., evidence of progression within 2-3 courses of beginning initial platinum-based therapy)

• Patients with platinum-sensitive disease must have known BRCA mutations

• Basal-like breast cancer, defined as estrogen and progesterone receptor-negative, HER2-negative, and/or expression profile of EGFR and cytokeratins 5/6 consistent with basal phenotype

• "Triple-negative" phenotype (i.e., negative hormone and HER2 receptors) allowed

• Patients with known "triple-negative" phenotype but unknown basal phenotype will have their tumor blocks assessed for basal markers

• Progressive disease after standard therapy OR no acceptable standard treatment options available

• Patients without a known BRCA mutation must have archived tumor tissue samples available for assessment of BRCA1/2 protein expression by immunohistochemistry

• Patients without a known, documented BRCA mutation from Myriad Genetic Laboratories must have a probability of harboring a BRCA gene mutation as assessed by BRCAPRO computer program

• Patients with a probability of harboring a BRCA gene mutation of ≥ 20% must undergo formal BRCA testing by Myriad Genetic Laboratories

• Patients with a diagnosis of a BRCA mutation based on a non-Myriad test must undergo Myriad BRCA gene sequencing

• Known deleterious BRCA1 or 2 mutation or a mutation of uncertain significance allowed

• Patients enrolled on dose levels VI-IX must be willing to undergo skin biopsies and hair sample collection before starting treatment and on day 4

• Patients who are receiving therapeutic doses of anticoagulation are exempt

• Patients with BRCA mutations who are enrolled in the 6-patient expansion group at the MTD (or dose level IX) must agree to tumor biopsies

• Tumors must be easily accessible for biopsies with low likelihood of complication

• Patients should not be on therapeutic doses of anticoagulation

• Patients with BRCA mutations who are enrolled in the 6-12 patient expansion group at the MTD (or dose level IX) must agree to tumor biopsies; therefore patients enrolled in this cohort should have tumors easily accessible for biopsies with low likelihood of complication and these patients should not be on therapeutic doses of anticoagulation

• Hormone receptor status not specified

• Menopausal status not specified

• ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)

• Life expectancy > 3 months

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Bilirubin ≤ 2.0 mg/dL

• Transaminases ≤ 2.5 times upper limit of normal

• Creatinine normal OR creatinine clearance > 50 mL/min

• Not pregnant or nursing

• Fertile patients must use effective contraception

• HIV infection allowed provided CD4 count > 500/mm³

• Able to swallow pills

• No concurrent uncontrolled 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 situation that would limit compliance with study requirements

• No concurrent protease inhibitors for patients with HIV infection

• Recovered from all prior therapy

• More than 4 weeks since prior major surgery, radiotherapy, or chemotherapy (6 weeks for nitrosoureas or mitomycin C)

• At least 4 weeks since prior flutamide (6 weeks for bicalutamide) for prostate cancer

• Concurrent ongoing luteinizing hormone-releasing hormone agonist therapy for prostate cancer required

• Concurrent IV bisphosphonates for bone metastases or hypercalcemia allowed provided treatment was initiated prior to study entry

• No concurrent chemotherapy

• No other concurrent investigational agents

• No other concurrent anticancer therapy

• 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 and must have a life expectancy secondary to that of 3 months or greater to be eligible

• Active seizure or history of seizure disorder are excluded

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Shannon Puhalla

Principal Investigator

U.S.A.
California
	Duarte
	City of Hope Comprehensive Cancer Center
		Robert J. Morgan	Ph: 626-256-4673
			Email: rmorgan@coh.org
		Robert J. Morgan	Principal Investigator
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Agustin A. Garcia	Ph: 323-865-0832
			Email: aagarcia@usc.edu
		Agustin A. Garcia	Principal Investigator
	Sacramento
	University of California Davis Cancer Center
		David R. Gandara	Ph: 916-734-3772
			Email: david.gandara@ucdmc.ucdavis.edu
		David R. Gandara	Principal Investigator
	South Pasadena
	City of Hope Medical Group, Incorporated
		Stephen C. Koehler	Ph: 626-396-2900
			Email: Skoehler@cohmg.com
		Stephen C. Koehler	Principal Investigator
New Jersey
	New Brunswick
	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
		Antoinette R. Tan	Ph: 732-235-6777
			Email: tanan@umdnj.edu
		Antoinette R. Tan	Principal Investigator
Pennsylvania
	Hershey
	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
		Chandra P. Belani	Ph: 717-531-1078
			Email: cbelani@psu.edu
		Chandra Prakash Belani	Principal Investigator
	Pittsburgh
	UPMC Cancer Centers
		Shannon L. Puhalla	Ph: 412-641-5792
			Email: puhallasl@upmc.edu
		Shannon Puhalla	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00892736
Information obtained from ClinicalTrials.gov on March 26, 2013

Back to Top