Olaparib for BRCAness Phenotype in Pancreatic Cancer

Inclusion Criteria:

1. Patients with histologically or cytologically confirmed metastatic adenocarcinoma of
the pancreas.

2. Family history: one or more close blood relative with ovarian carcinoma at any age or
breast cancer age 50 or younger or two relatives with breast, pancreatic or prostate
cancer (Gleason 7 or higher) at any age, or patients with Ashkenazi Jewish ancestry.
However, patients with previously identified genetic aberrations that are associated
with HRD will be eligible even in the absence of family history [e.g. somatic BRCA
mutation, Fanconi Anemia gene, ATM or RAD51 mutations].

3. Patients must be germline BRCA 1 or 2 negative. (Note: If BRCA status was previously
determined, that result is acceptable but documentation of status must be available;
subjects with unknown status will be referred to genetic counselling for BRCA testing
as per standard of care.) and/or patients with previously identified genetic
aberrations that are associated with HRD will be eligible even in the absence of
family history [e.g. somatic BRCA mutation, Fanconi Anemia gene, ATM or RAD51
mutations].

4. Patients must have received at least one prior therapy for metastatic disease to be
eligible.

5. Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >/=
20 mm with conventional techniques or as >/= 10 mm with spiral CT scan.

6. All treated patients have the option to undergo pre-treatment biopsy (liver, omentum,
lung or lymph node) to be eligible.

7. Patients with prior malignancy and treated with no evidence of active disease, and
more than 2 years from initial diagnosis are eligible.

8. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (Karnofsky >70).

9. Patients must have adequate organ and marrow function as defined below: leukocytes >/=
3,000 cells/mm^3; absolute neutrophil count >/= 1,500 cells/mm^3; platelets >/= 75,000
cells/mm^3; hemoglobin >/= 9 g/dl (no blood transfusions within 4 weeks prior to
enrollment); total bilirubin < 1.5 X institutional upper limit of normal (IULN);
AST(SGOT)/ALT(SGPT) with liver metastasis; creatinine not greater than Upper Institutional limits OR
creatinine clearance >/= 60 mL/min/1.73 m^2 for patients with creatinine levels above
institutional normal.

10. International Normalized Ratio (INR) < 1.5.

11. Patients must be >/= 18 years of age.

12. Women of childbearing potential (defined as not post-menopausal for 12 months or no
previous surgical sterilization) and fertile men must agree to use two highly
effective forms of contraception while they are receiving study treatment and for 30
days after last dose of study drug. Male subjects must agree to refrain from sperm
donation during the study and for 30 days after the last dose of study drugs.

13. Ability to understand and the willingness to sign a written informed consent document.
Signed informed consent form must be obtained prior to initiation of study evaluations
and/or activities.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia and myocardial infarction (MI) within 3
months of initiation of therapy.

2. Patients whose tumors are deemed to be platinum-refractory will be excluded from the
trial.

3. Pregnancy or lactation.

4. Patient has active and uncontrolled bacterial, viral, or fungal infection(s) requiring
systemic therapy.

5. Patient has undergone major surgical resection within 4 weeks prior to enrollment.

6. Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy
within 2 weeks prior to study entry.

7. Patient has serious medical risk factors involving any of the major organ systems such
that the investigator considers it unsafe for the patient to receive an experimental
research drug.

8. Serious psychiatric or medical conditions that could interfere with treatment.

9. Major bleeding in the last 4 weeks prior to study entry.

10. Concomitant use of CYP3A4 inhibitors.

11. Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470msec.
(Fredericia's scale).