This phase I/II trial studies the safety, side effects and best dose of M3814 and to see how well it works when given together with radiation therapy in treating patients with pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced). M3814 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving M3814 and hypofractionated radiation therapy together may be safe, tolerable and/or more effective than radiation therapy alone in treating patients with locally advanced pancreatic cancer.
Patients must have pathologically confirmed pancreatic adenocarcinoma. Patients with alternative or mixed histologies (i.e., squamous, neuroendocrine, acinar, colloid) are not eligible
Received 4-6 months of induction chemotherapy with fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX), fluorouracil, liposomal irinotecan, leucovorin, oxaliplatin (NALIRIFOX), or gemcitabine/Abraxane, as per standard of care
Solid tumor contact with superior mesenteric artery > 180 degrees
Solid tumor contact with the celiac axis > 180 degrees
Patients who have completed induction chemotherapy less than 2 weeks or more than 8 weeks prior to study enrollment
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and neuropathy grade =< 2
Patients who are receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to M3814 (peposertib)
Parallel
Biopsy Procedure
Procedure/SurgeryUndergo tissue collection
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Hypofractionated Radiation Therapy
RadiationUndergo hypofractionated radiation therapy
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Peposertib
DrugGiven PO
Placebo Administration
Other interventionGiven PO
Maximum tolerated dose (Phase I)
Recommended phase 2 dose (Phase I)
Progression-free survival rate (Phase II)
The 95% confidence intervals will be provided.
Overall survival (OS)
Will be analyzed using a log-rank test to test for differences between the treatment groups in survival experience. The proportion of patients who survive through 2 years (i.e. the 2-year OS rate) will be compared between arms using Kaplan-Meier estimates.
Two-year OS
Defined as the rate of patient survival at 2 years following completion of study treatment (based on Kaplan-Meier method).
Overall response rate
Defined as the rate of complete or partial response by imaging following study treatment as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Will be summarized and compared between arms.
Disease control rate
Defined as rate of stable disease, complete or partial response by imaging as assessed by RECIST v1.1. Will be summarized and compared between arms.
Gene signature of cell-free DNA from peripheral blood
Results of cell-free DNA analysis will be compared pre- and post-treatment and reported descriptively.
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