Trial 0S-09-1

A Phase I Study of Chronically-Dosed, Single-Agent, ABT-888 in Patients with Either BRCA 1/2-Mutated Cancer; Platinum-Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer; or Basal-Like Breast Cancer.

Type: Cancer Therapy
Phase: Phase I
Status: Open to Accrual
Treatments: Chemotherapy: Systemic
Randomized: No
Defintions of terms and FAQ about clinical trials.

Trial Leaders/Researchers: Agustin Garcia, M.D.
Other Trial Staff: Kristy Watkins, R.N., Yvonne Flores, D.M., Anayansi Miloud, D.M., Xiomara Menendez, R.N., Molly Oswald, R.N.

Staff may log in to see study documents.

You may participate in this study if:

	Requirement
1	Patients must have histologically or cytologically confirmed solid tumors that fulfill at least one of the following 3 criteria: 1. Have a documented BRCA1/2 mutation and a BRCA related malignancy (primarily breast or ovarian cancers, but also may include prostate or pancreatic cancers) or 2. Platinum-refractory ovarian, fallopian tube, or primary peritoneal cancer or 3. Basal-like breast cancer whose disease has progressed following standard therapy or who have no acceptable standard treatment options.
2	All patients without a known, documented BRCA mutation from Myriad Genetic Laboratories must have a probability of harboring a BRCA gene mutation assessed by BRCAPRO computer program. All patients in whom the probability of having a genetic mutation is greater than or equal to 20% must have formal BRCA testing done through Myriad Genetic Laboratories in order to participate in the study. Although various research based tests have been developed to detect BRCA mutations, due to the fact that these are not FDA or CLIA approved and therefore not reportable to patients, if a patient has diagnosis of a BRAC mutation based on a non- Myriad test, then they must undergo Myriad BRCA gene sequencing to be eligible. Patients are eligible whether they have a known deleterious BRCA 1 or 2 mutation or a mutation of uncertain significance. If a patient refuses BRCA testing, then they are ineligible for the study.
3	Platinum-refractory is defined as progression or recurrence within 6 months of initial platinum response. Platinum-resistant is defined as having no prior response to platinum (i.e. evidence of progression within 2-3 cycles of beginning initial platinum-based treatment) and platinum-resistant patients are excluded. The only platinum-sensitive patients that are eligible are those with known BRCA mutations.
4	Basal-like breast cancer will be defined as estrogen and progesterone receptor negative, HER2 negative, and/or having expression profile of EGFR and cytokeratins 5/6, consistent with basal phenotype. Breast cancer patients with “triple-negative” phenotype (negative hormone and HER2 receptors) are eligible to participate in this trial. Patients who are only known to be “triple-negative” but unknown basal phenotype will have their tumor blocks assessed for basal markers.
5	All enrolled patients without a known BRCA mutation must have archived tumor tissue available for assessment of BRCA 1/2 protein expression by immunohistochemistry, as well as other correlative studies.
6	It is optional for patients with a known BRCA mutation to provide archived tissue for correlative studies.
7	There are no limitations on the amount of prior therapies received. However, no major surgery, radiation or chemotherapy within four weeks prior to study enrollment except for mitomycin C and nitrosoureas, in which case it is 6 weeks; Patients must be recovered from toxicities of prior therapies to at least eligibility levels
8	Age greater than or equal to 18 years.
9	ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%).
10	Life expectancy of greater than 3 months
11	Patients must have acceptable organ and marrow function as defined below: • Transaminases less than or equal to 2.5 x ULN • Bilirubin less than or equal to 2.0 • Creatinine less than or equal to ULN or a creatinine clearance >50 (calculated by Cockroft-Gault formula) if creatinine > ULN • Neutrophils greater than or equal to 150 • Platelets greater than or equal to 100,000
12	The effects of ABT-888 on the developing human fetus are unknown. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
13	Patient must have signed and dated IRB approved informed consent and HIPAA authorization forms.
14	Ability to swallow pills
15	Patients with controlled CNS disease (treated brain metastases) and life expectancy of 3 months or greater are eligible.

You may not participate in this study if:

1	Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
2	Patients may not be receiving any other investigational agents. • Patients with prostate cancer must continue ongoing LhRH agonist therapy and discontinue antiandrogens at least 6 weeks (for bicalutamide) or 4 weeks (flutamide) prior to study entry. Patients with bone metastases or hypercalcemia who began intravenous bisphosphonate treatment prior to study entry may continue this treatment.
3	Patients with uncontrolled CNS metastasis and life expectancy secondary to that of less than 3 months are not eligible.
4	Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
5	HIV infected patients on protease inhibitors are ineligible due to potential for drug-drug interactions and increased drug effects. HIV infected patients with adequate CD4 counts (>500) and not on protease inhibitors are eligible.
6	Pregnant women are excluded from this study because ABT-888 is a PARP inhibitor which affects DNA repair pathways with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ABT-888, breastfeeding should be discontinued if the mother is treated with ABT-888.

For further information on a study, please contact the Clinical Investigation Support Office at (323) 865-0451, or clinical.trials@med.usc.edu.

To schedule a consultation with the hospital, please call our New Patient Referrals Office at (323) 865-3111.