| 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. |
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. |