Phase II Study of Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma

  • STATUS
    Recruiting
  • End date
    Jun 1, 2025
  • participants needed
    20
  • sponsor
    National Cancer Institute (NCI)
Updated on 20 September 2022

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.

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.

Details
Condition Pancreatic Acinar Cell Carcinoma
Treatment olaparib
Clinical Study IdentifierNCT05286827
SponsorNational Cancer Institute (NCI)
Last Modified on20 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Histological or cytological diagnosis of Pancreatic Acinar Cell Carcinoma (PACC) as confirmed by NIH Laboratory of Pathology
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 RECIST 1.1
Age >=18 years
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 sequalae 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 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
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
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
Participants must agree to abstain from consuming grapefruit juice throughout the
duration of study treatment with olaparib
Ability of subject to understand and the willingness to sign a written informed
consent document

Exclusion Criteria

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 GI
disorders likely to interfere with absorption of study medication
Participants with HIV are excluded even if viral load is undetectable
Active hepatitis B or C
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
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
Participants with myelodysplastic syndrome/acute myeloid leukemia 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
Previous allogenic bone marrow transplant or double umbilical cord blood
transplantation (dUCBT)
Women who are breastfeeding and unwilling to stop
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
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
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
Participants with large volume ascites, serum albumin < 2.5 mg/dL, or having received
paracentesis within the last 4 weeks
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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note