Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma

-INCLUSION CRITERIA:

1. Histological or cytological diagnosis of pancreatic acinar cell carcinoma (PACC) as confirmed by National Institutes of Health (NIH) Laboratory of Pathology (LP).
2. Participants must have received one prior line of combination chemotherapy (or be ineligible to receive combination chemotherapy) with tumor still not amenable for potentially curative resection or be ineligible to receive combination chemotherapy. There is no limit on the number of prior therapies.
3. Access to medical records from past treatment
4. Measurable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
5. Age \>=18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status \<=1.
7. At least 3 weeks from previous chemotherapy or radiation therapy prior to planned start of treatment.
8. At least 30 days or 5 half-lives (whichever is greater) since receipt of any investigational therapy prior to planned start of treatment.
9. Fully recovered from all reversible sequelae and \>=2 weeks from major surgery or from minor surgical procedure such as biliary or duodenal stenting prior to planned start of treatment.
10. At least 2 weeks since last use of known strong cytochrome P450 (CYP) (CYP3A) inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil).
11. At least 5 weeks since last use of phenobarbital, enzalutamide, and at least 3 weeks since last use of other strong (e.g., phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (e.g., bosentan, efavirenz, modafinil) CYP3A inducers.
12. Adequate organ and marrow function as measured within 28 days prior to study treatment as defined below:

    * leukocytes \>=3,000/mcL
    * absolute neutrophil count \>=1,500/mcL
    * hemoglobin \>= 10 g/dL with no blood transfusion within the last 28 days
    * platelets \>=100,000/mcL
    * total bilirubin within 1.5x normal institutional upper limit of normal (ULN)
    * Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) \<= institutional ULN unless liver metastases are present in which case they may be \<=5x ULN
    * Creatinine must be within normal range, OR \>=51 mL/min per the formula below\* or measured by 24-hour urine test

      * Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (x F) serum/ creatinine (mg/dL) x 72\^a, where F=0.85 for females and F=1 for males

    This list includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
13. The effects of olaparib on the developing human fetus are unknown. For this reason and because PARP inhibitor agents are known to be teratogenic, individuals of child-bearing potential (IOCBP) and individual able to father a child must agree to use adequate contraception prior to study entry and for the duration of study participation.
14. Participants must agree to abstain from consuming grapefruit juice throughout the duration of study treatment with olaparib.
15. Ability of participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

1. History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib.
2. Participants unable to swallow orally administered medication or suffering from gastrointestinal (GI) disorders likely to interfere with absorption of study medication.
3. Participants with human immunodeficiency virus (HIV) are excluded even if viral load is undetectable
4. Active hepatitis B (HBV) or hepatitis C virus (HCV)
5. Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QT corrected by Fridericia's formula (QTcF) prolongation \>500 ms, electrolyte disturbances, etc.), or participants with congenital long QT syndrome.
6. Recent (within 3 months) myocardial infarction
7. Unstable angina pectoris.
8. Symptomatic congestive heart failure
9. Uncontrolled major seizure disorder
10. Superior vena cava syndrome
11. Extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan
12. Psychiatric illness/social situations (within the last 3 months) that would limit compliance with study requirements or prohibits obtaining informed consent
13. Uncontrolled intercurrent illness or participants considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active uncontrolled infection as documented in prior records or suggested by medical history, physical examination or standard clinical assessments such as imaging and laboratory studies
14. Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
15. Solid or liquid malignancy other than PACC unless curatively treated with no evidence of disease for \>=5 years, except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.
16. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
17. Participants who are nursing and unwilling to stop.
18. Symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. Brain metastases are considered uncontrolled if the dose of corticosteroid being provided for control of brain metastases has been titrated in the 4 weeks prior to start of treatment.
19. Participants with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for \>=28 days. Participants with unstable spinal cord compression are ineligible even if previously treated.
20. Participants with large volume ascites, serum albumin \< 2.5 mg/dL, or having received paracentesis within the last 4 weeks
21. Participants with persistent toxicities \> Grade 2 or with new Grade 2 events within the last 2 weeks per Common Terminology Criteria for Adverse Event (CTCAE) version 5 caused by previous cancer therapy.