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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Administered orally (300 mg) twice daily continuously for 28-day cycles as clinically indicated.
Screening.
Screening. Baseline Cycle 1, Day 1 (≤7 days), and subsequent Cycles, Day 1 (+/- 7 days) every 8 weeks.
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)
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
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.
Time frame: 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.
Time frame: 1-year
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Calculated at baseline and assessed every 28 days for an average of 0.158 months.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.