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Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05286827
Recruitment Status : Recruiting
First Posted : March 18, 2022
Last Update Posted : August 11, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

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 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.


Condition or disease Intervention/treatment Phase
Pancreatic Acinar Cell Carcinoma Drug: Olaparib Phase 2

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 (~30%) response rates in the first-line setting.
  • PACC pathological specimens demonstrate evidence of high chromosomal instability, a hallmark of 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 FDA approved for the treatment of BRCA-mutant homologous recombination repair (HRR) deficient cancers.
  • As PACC has multiple hallmarks of 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 platinum-sensitive advanced pancreatic acinar cell carcinoma (PACC)

Eligibility:

  • Participants must have advanced previously treated PACC
  • Participants must not have platinum-resistant disease
  • Age >=18 years
  • Adequate organ and bone marrow function

Design:

  • This is a phase II, single arm, single center study of olaparib in subjects with advanced previously treated PACC.
  • All subjects will take olaparib by mouth twice daily for up to two years or until disease progression or intolerable side effects.
  • Subjects will be assessed for safety (continuously) and efficacy (every 8 weeks).
  • Up to 13 evaluable participants will be enrolled.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma
Estimated Study Start Date : August 16, 2022
Estimated Primary Completion Date : June 1, 2024
Estimated Study Completion Date : June 1, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Olaparib

Arm Intervention/treatment
Experimental: Arm 1
Olaparib, taken orally, twice daily
Drug: Olaparib
Administered orally (300 mg) twice daily continuously for 21-day cycles for up to 2 years.




Primary Outcome Measures :
  1. antitumor activity [ Time Frame: 1 year post-last dose of olaparib ]
    Objective response rate (ORR, CR+PR)


Secondary Outcome Measures :
  1. anti-tumor efficacy [ Time Frame: 1 year after last olaparib treatment ]
    Disease control rate, median duration of treatment response, median progression-free survival (PFS) and median overall survival (OS)

  2. safety [ Time Frame: from start of treatment to 30 days after last treatment ]
    AEs and SAEs of olaparib



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

-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 72a, 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 known to have disease resistant to platinum chemotherapy will be excluded. A patient has platinum-resistant disease if: a) develop progression of disease during prior platinum-based chemotherapy (including cisplatin, carboplatin, and/or oxaliplatin), and/ or b) develop recurrence/ progressive disease within 3 months after completion of platinum-containing adjuvant therapy. If the platinum component of a combination regimen is dropped prior to progression of disease, the patient does NOT have platinum- resistant disease. Disease will be considered progressive if there was radiologic evidence of progression as reported by prior CT evidence or physician assessment, or >= 25% composite increase in relevant tumor marker on two sequential measurements at least 1 week apart. Completion of adjuvant therapy is defined as receiving the intended number of cycles.
  21. Participants with large volume ascites, serum albumin < 2.5 mg/dL, or having received paracentesis within the last 4 weeks
  22. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05286827


Contacts
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Contact: NCI Medical Oncology Referral Office (240) 760-6050 ncimo_referrals@nih.gov
Contact: Christine C Alewine, M.D. (240) 760-6146 alewinecc@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY dial 711    ccopr@nih.gov   
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Christine C Alewine, M.D. National Cancer Institute (NCI)
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT05286827    
Other Study ID Numbers: 10000596
000596-C
First Posted: March 18, 2022    Key Record Dates
Last Update Posted: August 11, 2022
Last Verified: July 5, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All 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 dbGaP.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data available during the study and indefinitely. @@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.@@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Poly-Adp Ribose Polymerase (Parp)-1 Inhibitor
Homologous Recombination Repair
Platinum-Sensitive
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Acinar Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents