Phase II Study of Olaparib in Subjects With Advanced Pancreatic Acinar Cell Carcinoma
Status:
Not yet recruiting
Trial end date:
2025-06-01
Target enrollment:
Participant gender:
Summary
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.