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.

Background: * Pancreatic Acinar Cell Carcinoma (PACC) is a rare pancreatic tumor, representing 0.5-1% of all pancreatic malignancies. * PACC is commonly advanced at presentation and median overall survival in this population is poor. * PACC is pathologically and biochemically distinct from pancreatic adenocarcinoma. * No clinical trials for PACC have ever been reported. * Patients are most commonly treated with combination regimens used for either pancreatic or colon adenocarcinoma with poor (approximately 30%) response rates in the first line setting. * PACC pathological specimens demonstrate evidence of high chromosomal instability, a hallmark of deoxyribonucleic acid (DNA) repair deficiency. * Data derived from ovarian and prostate cancer patients has demonstrated that mutations in DNA repair genes can define subgroups of cancer patients with distinct vulnerabilities to DNA damage response inhibitors. * Olaparib is a Poly-ADP ribose polymerase (PARP)-1 inhibitor that has been Food and Drug Administration (FDA) approved for the treatment of BReast CAncer genes 1 and 2 (BRCA)-mutant homologous recombination repair (HRR) deficient cancers. * As PACC has multiple hallmarks of homologous recombination repair (HRR) deficiency, we hypothesize that PACC will be sensitive to PARP inhibition with olaparib. * Pre-clinical modeling of PACC has been very limited with no currently available animal models or cell lines, which precludes testing this hypothesis in the laboratory setting. Objective: \- To assess the anti-tumor activity of single agent olaparib, a PARP inhibitor, in participants with advanced pancreatic acinar cell carcinoma (PACC) Eligibility: * Participants must have advanced previously treated PACC * Age \>=18 years * Adequate organ and bone marrow function Design: * This is a phase II, single arm, single center study of olaparib in participants with advanced previously treated PACC. * All participants will take olaparib by mouth twice daily for up to two years or until disease progression or intolerable side effects. * Participants will be assessed for safety (continuously) and efficacy (every 8 weeks). * Up to 13 evaluable participants will be enrolled.