Overview

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 21-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.

Eligibility

-INCLUSION CRITERIA:

1. Histological or cytological diagnosis of Pancreatic Acinar Cell Carcinoma (PACC) as confirmed by NIH Laboratory of Pathology.
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 RECIST 1.1.
5. Age >=18 years.
6. 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 sequalae 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 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)
    • AST(SGOT)/ALT(SGPT) <= institutional ULN unless liver metastases are present in which case they may be <=5x ULN
    • Creatinine clearance must be >51 mL/min as estimated using the Cockroft-Gault equation* 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, women of child-bearing
             potential and men 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 subject 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 GI
             disorders likely to interfere with absorption of study medication.
          3. Participants with HIV are excluded even if viral load is undetectable
          4. Active hepatitis B or C
          5. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as
             judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic
             arrhythmia, congestive heart failure, 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. Participants with myelodysplastic syndrome/acute myeloid leukemia 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. Women who are breastfeeding and unwilling to stop.
         18. Participants with 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.