Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma

NCT05286827 | Terminated Phase 2 Results

• 2 other identifiers: 10000596000596-C
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pancreatic Acinar Cell Carcinoma

Keywords

Poly-Adp Ribose Polymerase (Parp)-1 Inhibitor; Homologous Recombination Repair; Platinum-Sensitive

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Percentage of Participants With Partial Response, Complete Response, and/or Stable Disease Reported Along With a 95% Confidence Interval

  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

  From start of treatment to 30 days after last treatment, up to an average of 30 days

• Median Duration of Treatment Response

  1-year after response noted

• Median Progression-free Survival (PFS) Reported Along With a 95% Confidence Interval

  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

  Calculated from the on-study date until the date of death, an average of 11 months.

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  From the first study intervention, Study Day 1, through 30 days following the last dose of the study medication, an average of 30 days

Study Arms (1)

Arm 1 Cohort 1 Olaparib in Pancreatic Acinar Cell Carcinoma

EXPERIMENTAL

Olaparib, taken orally, twice daily

Drug: Olaparib; Diagnostic Test: ECG; Diagnostic Test: CT CAP; Procedure: Tumor Biopsy

Interventions

Olaparib DRUG

Administered orally (300 mg) twice daily continuously for 28-day cycles as clinically indicated.

Also known as: Lynparza

Arm 1 Cohort 1 Olaparib in Pancreatic Acinar Cell Carcinoma

ECG DIAGNOSTIC_TEST

Screening.

Also known as: Electrocardiogram

Arm 1 Cohort 1 Olaparib in Pancreatic Acinar Cell Carcinoma

CT CAP DIAGNOSTIC_TEST

Screening. Baseline Cycle 1, Day 1 (≤7 days), and subsequent Cycles, Day 1 (+/- 7 days) every 8 weeks.

Also known as: Computed tomography chest, abdomen, and pelvis

Arm 1 Cohort 1 Olaparib in Pancreatic Acinar Cell Carcinoma

Tumor Biopsy PROCEDURE

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)

Also known as: Tumor Bx

Arm 1 Cohort 1 Olaparib in Pancreatic Acinar Cell Carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological diagnosis of pancreatic acinar cell carcinoma (PACC) as confirmed by National Institutes of Health (NIH) Laboratory of Pathology (LP).
• 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.
• Access to medical records from past treatment
• Measurable disease, per Response Evaluation Criteria in Solid Tumors (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 planned start of treatment.
• At least 30 days or 5 half-lives (whichever is greater) since receipt of any investigational therapy prior to planned start of treatment.
• 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.
• 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).
• 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.
• 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

You may not qualify if:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib.
• Participants unable to swallow orally administered medication or suffering from gastrointestinal (GI) disorders likely to interfere with absorption of study medication.
• Participants with human immunodeficiency virus (HIV) are excluded even if viral load is undetectable
• Active hepatitis B (HBV) or hepatitis C virus (HCV)
• 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.
• 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 limit compliance with study requirements or prohibits obtaining informed consent
• 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
• Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

olaparib; Electrocardiography

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Limitations and Caveats

This study was closed early. Data should be interpreted with caution given the small sample size.

Results Point of Contact

• Title: Dr. Anish Thomas
• Organization: National Cancer Institute

anish.thomas@nih.gov

240- 760-7343

Study Officials

• Anish Thomas, MBBS, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 12, 2022
• First Posted: March 18, 2022
• Study Start: December 14, 2023
• Primary Completion: December 18, 2024
• Study Completion: September 25, 2025
• Last Updated: March 11, 2026
• Results First Posted: March 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• 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.

Locations

US (1)