Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma

Phase

Condition

Pancreatic Disorders

Carcinoma

Treatment

Olaparib

Clinical Study ID

NCT05286827

10000596

000596-C

Ages > 18
All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

-INCLUSION CRITERIA:

Histological or cytological diagnosis of pancreatic acinar cell carcinoma (PACC) asconfirmed by NIH Laboratory of Pathology (LP).
Participants must have received one prior line of combination chemotherapy (or beineligible to receive combination chemotherapy) with tumor still not amenable forpotentially curative resection or be ineligible to receive combination chemotherapy.There is no limit on the number of prior therapies.
Access to medical records from past treatment
Measurable disease, per RECIST 1.1.
Age >=18 years.
Eastern Cooperative Oncology Group (ECOG) performance status <=1.
At least 3 weeks from previous chemotherapy or radiation therapy prior to plannedstart of treatment.
At least 30 days or 5 half-lives (whichever is greater) since receipt of anyinvestigational therapy prior to planned start of treatment.
Fully recovered from all reversible sequalae and >=2 weeks from major surgery orfrom minor surgical procedure such as biliary or duodenal stenting prior to plannedstart of treatment.
At least 2 weeks since last use of known strong CYP3A inhibitors (e.g.,itraconazole, telithromycin, clarithromycin, protease inhibitors boosted withritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir)or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem,fluconazole, verapamil).
At least 5 weeks since last use of phenobarbital, enzalutamide, and at least 3 weekssince 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.
Adequate organ and marrow function as measured within 28 days prior to studytreatment 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 formales This list includes eligibility-defining laboratory value requirements for treatment;laboratory value requirements should be adapted according to local regulations andguidelines for the administration of specific chemotherapies.

The effects of olaparib on the developing human fetus are unknown. For this reasonand because PARP inhibitor agents are known to be teratogenic, individuals ofchild-bearing potential (IOCBP) and individual able to father a child must agree touse adequate contraception prior to study entry and for the duration of studyparticipation.
Participants must agree to abstain from consuming grapefruit juice throughout theduration of study treatment with olaparib.
Ability of participant to understand and the willingness to sign a written informedconsent document.

Exclusion

EXCLUSION CRITERIA:

History of allergic reactions attributed to compounds of similar chemical orbiologic composition to olaparib.
Participants unable to swallow orally administered medication or suffering fromgastrointestinal (GI) disorders likely to interfere with absorption of studymedication.
Participants with human immunodeficiency virus (HIV) are excluded even if viral loadis undetectable
Active hepatitis B (HBV) or hepatitis C virus (HCV)
Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversiblecardiac 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 QTsyndrome.
Recent (within 3 months) myocardial infarction
Unstable angina pectoris.
Symptomatic congestive heart failure
Uncontrolled major seizure disorder
Superior vena cava syndrome
Extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan
Psychiatric illness/social situations (within the last 3 months) that would limitcompliance with study requirements or prohibits obtaining informed consent
Uncontrolled intercurrent illness or participants considered a poor medical risk dueto a serious, uncontrolled medical disorder, non-malignant systemic disease oractive uncontrolled infection as documented in prior records or suggested by medicalhistory, physical examination or standard clinical assessments such as imaging andlaboratory studies
Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with featuressuggestive of MDS/AML.
Solid or liquid malignancy other than PACC unless curatively treated with noevidence of disease for >=5 years, except: adequately treated non-melanoma skincancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.
Previous allogenic bone marrow transplant or double umbilical cord bloodtransplantation (dUCBT).
Participants who are nursing and unwilling to stop.
Symptomatic uncontrolled brain metastases. A scan to confirm the absence of brainmetastases is not required. Brain metastases are considered uncontrolled if the doseof corticosteroid being provided for control of brain metastases has been titratedin the 4 weeks prior to start of treatment.
Participants with spinal cord compression unless considered to have receiveddefinitive treatment for this and evidence of clinically stable disease for >=28days. Participants with unstable spinal cord compression are ineligible even ifpreviously treated.
Participants with large volume ascites, serum albumin < 2.5 mg/dL, or havingreceived paracentesis within the last 4 weeks
Participants with persistent toxicities > Grade 2 or with new Grade 2 events withinthe last 2 weeks per Common Terminology Criteria for Adverse Event (CTCAE) version 5caused by previous cancer therapy.

Study Design