Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma

Phase II Study of 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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Acinar Cell Carcinoma
• Intervention / Treatment: Drug: Olaparib; Diagnostic test: ECG; Diagnostic test: CT CAP; Procedure: Tumor Biopsy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

-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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm 1 Cohort 1 Olaparib in Pancreatic Acinar Cell Carcinoma; Olaparib, taken orally, twice daily

Drug: Olaparib; Administered orally (300 mg) twice daily continuously for 28-day cycles as clinically indicated.; Other Names: Lynparza; Diagnostic test: ECG; Screening.; Other Names: Electrocardiogram; Diagnostic test: CT CAP; Screening. Baseline Cycle 1, Day 1 (≤7 days), and subsequent Cycles, Day 1 (+/- 7 days) every 8 weeks.; Other Names: Computed tomography chest, abdomen, and pelvis; Procedure: Tumor Biopsy; Optional. Baseline Cycle 1, Day 1 (≤7 days), subsequent Cycles, Day 1 (+/- 7 days; once only, Cycle 2 preferred), and end of treatment (14-30 days after last treatment); Other Names: Tumor Bx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants With Partial Response (PR) or Complete Response (CR) Reported Along With a 95% Two-sided Confidence Interval	Objective response rate (ORR) is defined as the proportion of participants with partial response or complete response reported along with a 95% two-sided confidence interval. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.	1-year
Proportion of Participants With Partial Response or Complete Response Reported Along With a 80% Two-sided Confidence Interval	Objective response rate (ORR) is defined as the proportion of participants with partial response or complete response reported along with an 80% two-sided confidence interval. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.	1-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Partial Response, Complete Response, and/or Stable Disease Reported Along With a 95% Confidence Interval	Disease control rate is defined as the percentage of participants with partial response, complete response, and/or stable disease. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.	1-year
Number of Treatment-related Serious Adverse Events by Grade and Type as Defined by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Here is the number of treatment-related serious adverse events as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse events.	From start of treatment to 30 days after last treatment, up to an average of 30 days
Median Duration of Treatment Response	Median duration of treatment responses will be reported using the Kaplan-Meier method from the date a response is identified until the date a response ends (by progression or other reason), or the response is continuing, in which case the duration will be censored. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Complete Response is disappearance of all target lesions. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.	1-year after response noted
Median Progression-free Survival (PFS) Reported Along With a 95% Confidence Interval	PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. PFS will be determined using the Kaplan-Meier method and will be reported along with a 95% confidence interval. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.	Calculated from on-study date until the date of progression or death without progression as events with participants censored if they do not have an event by the date of last known follow-up, an average of 1.6 months.
Median Overall Survival (OS) Reported Along With a 95% Confidence Interval	Overall survival (OS) is defined as the length of time from start of treatment until death from any cause estimated using the Kaplan-Meier method.	Calculated from the on-study date until the date of death, an average of 11 months.
Months to Best Response in Participants Assessed Using Serum Lipase (Tumor Marker in Pancreatic Acinar Cell Carcinoma)	Best response in serum lipase (tumor marker in pancreatic acinar cell carcinoma) was assessed for each treated participant (defined as greatest decrease from baseline measurement during the treatment course) tested for statistical significance of the change by a Wilcoxon signed rank test with a two-tailed p-value, and the median and full range was calculated.	Calculated at baseline and assessed every 28 days for an average of 0.158 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	From the first study intervention, Study Day 1, through 30 days following the last dose of the study medication, an average of 30 days

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Chen Zhao, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2023
• Primary Completion (Actual): December 18, 2024
• Study Completion (Actual): September 25, 2025

Study Registration Dates

• First Submitted: March 12, 2022
• First Submitted That Met QC Criteria: March 17, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: July 23, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Poly-Adp Ribose Polymerase (Parp)-1 Inhibitor; Homologous Recombination Repair; Platinum-Sensitive
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Acinar Cell; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Cardiovascular; Heart Function Tests; Electrodiagnosis; olaparib; Electrocardiography
• Other Study ID Numbers: 10000596; 000596-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No