Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma

Background: Pancreatic Acinar Cell Carcinoma (PACC) is a rare pancreatic tumor. People with PACC usually present with advanced disease, and their prognosis is poor. Researchers want to learn if a cancer drug called olaparib can help. Objective: To see if olaparib is an effective treatment for PACC. Eligibility: People aged 18 and older with PACC whose cancer did not respond to previous treatments or is not eligible for surgery. Design: Participants will be screened with the following: Medical history Physical exam Blood and urine tests Electrocardiogram (to test heart function) Computed tomography (CT) scans Pregnancy test (if needed) Tumor biopsy (if a sample is not available) Treatment will be given in 28-day cycles. Participants will take olaparib by mouth twice daily for each cycle. They will keep a medicine diary. They will receive treatment for up to 2 years. They may stop treatment early if their cancer gets worse or they have serious side effects. Participants will have study visits at the beginning of each cycle. At visits, they will repeat some screening tests. They will be asked about any changes in medicines they are taking and how they are feeling. They will have CT scans every 8 weeks starting in cycle 2. Participants will give blood samples for research. They may have optional tumor biopsies. Participants will have 2 follow-up visits in the 30 days after treatment ends or before they begin a new anti-cancer treatment. Then they will be contacted every 3 months by phone for 1 year. Participation will last for up to 3 years.

-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 \=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) \