Testing the Addition of a New Anti-cancer Drug, M3814 (Peposertib), to the Usual Radiotherapy in Patients With Locally Advanced Pancreatic Cancer

Recruiting now · Phase 1/Phase 2 · Has a placebo group

Conditions studied: Locally Advanced Pancreatic Adenocarcinoma, Stage III Pancreatic Cancer AJCC v8

In brief

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.

Key facts

Study ID

NCT04172532

Run by

National Cancer Institute (NCI)

People needed

92

Starts

2021-01-11

Expected to finish

2027-08-01

Last updated by the study team

2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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
• Patients must have locally advanced pancreatic cancer according to National Comprehensive Cancer Network (NCCN) Guidelines (version 1.2020) on pancreas protocol CT scan performed within 21 days of registration. Locally advanced disease is defined as any of the following:
• For head or uncinate process tumors:
• Solid tumor contact with superior mesenteric artery > 180 degrees
• Solid tumor contact with the celiac axis > 180 degrees
• Solid tumor contact with the common or proper hepatic arteries > 180 degrees or
• For pancreatic body or tail tumors:
• Solid tumor contact of > 180 degrees with the superior mesenteric artery or celiac axis
• Solid tumor contact with the celiac axis and aortic involvement or
• Unreconstructible superior mesenteric vein or portal vein due to tumor involvement or occlusion (can be due to tumor or bland thrombus)
• The determination of locally advanced pancreatic cancer and plan for non-operative treatment on this clinical trial must be confirmed through local multi-disciplinary review
• Measurable disease per response evaluation criteria in solid tumors (RECIST) version (v)1.1
• Age >= 18 years. Because no dosing or adverse event data are currently available on the use of M3814 (peposertib) in combination with hypofractionated radiation in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Leukocytes >= 4,000/mcL
• Absolute neutrophil count >= 1.5 x 10\^9/L.
• Hemoglobin >= 9 g/dL
• Platelets >= 100 x 10\^9/L
• Total bilirubin =< 2.0 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN
• Creatinine =< 1.5 x institutional ULN
• Glomerular filtration rate (GFR) >= 51 mL/min/1.73 m\^2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

You may not qualify if…

• 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)
• Evidence of distant metastatic disease
• More than 1 line of chemotherapy for the treatment of localized pancreatic cancer, unless the change in treatment was made only for toxicity
• Prior abdominal radiation
• Active inflammatory bowel disease or connective tissue disease
• Inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents
• History of anaphylactic reaction to iodinated intravenous (IV) contrast required for radiation simulation. Patients with mild reactions may be enrolled, but must receive premedications for contrast allergy prior to imaging
• Patients who cannot discontinue concomitant medications or herbal supplements that are strong inhibitors or strong inducers of cytochrome P450 (CYP) isoenzymes CYP3A4/5, CYP2C9, and CYP2C19. Concomitant use of substrates with a narrow therapeutic index that are metabolized by CYP1A2, CYP2B6, CYP2C8, and CYP3A4/5 are also excluded.
• Use caution with other substrates of CYP3A4/5, CYP1A2, CYP2B6, CYP2C8 and substrates of P-gp, BCRP, OCT1, OAT3, OATP1B1, OATP1B3, MATE1, and MATE-2K with a narrow therapeutic index. Close monitoring is advised.
• Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. (Patient Drug Interactions Handout and Wallet Card) should be provided to patients
• Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs). Patients may confer with the study doctor to determine if such medications can be discontinued. These must be discontinued >= 5 days prior to study treatment. Patients do not need to discontinue calcium carbonate. H2 blockers and antacids are allowed.
• Patients who have received a live attenuated vaccine within 30 days of dosing with M3814 (peposertib)
• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because M3814 (peposertib) is a DNA-protein kinase (PK) inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M3814 (peposertib), breastfeeding should be discontinued if the mother is treated with M3814 (peposertib)
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this investigational regimen

Where it is running

• University of Wisconsin Carbone Cancer Center - University Hospital — Madison, Wisconsin, United States (enrolling)
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care — Irvine, California, United States (enrolling)
• City of Hope at Irvine Lennar — Irvine, California, United States (enrolling)
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States (enrolling)
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States (enrolling)
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States (enrolling)
• Sibley Memorial Hospital — Washington D.C., District of Columbia, United States (enrolling)
• University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States (enrolling)
• Salina Regional Health Center — Salina, Kansas, United States (enrolling)
• University of Kansas Health System Saint Francis Campus — Topeka, Kansas, United States (enrolling)
• University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States (enrolling)
• University Health Truman Medical Center — Kansas City, Missouri, United States (enrolling)
• University of Kansas Cancer Center - North — Kansas City, Missouri, United States (enrolling)
• University of Kansas Cancer Center - Lee's Summit — Lee's Summit, Missouri, United States (enrolling)
• Cooperman Barnabas Medical Center — Livingston, New Jersey, United States (enrolling)
• Monmouth Medical Center — Long Branch, New Jersey, United States (enrolling)
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States (enrolling)
• Mount Sinai Hospital — New York, New York, United States (enrolling)
• NYP/Weill Cornell Medical Center — New York, New York, United States (enrolling)
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (enrolling)
• VCU Massey Comprehensive Cancer Center — Richmond, Virginia, United States (enrolling)
• University of Wisconsin Carbone Cancer Center - Eastpark Medical Center — Madison, Wisconsin, United States (enrolling)
• City of Hope Comprehensive Cancer Center — Duarte, California, United States (enrolling)
• University of Kansas Clinical Research Center — Fairway, Kansas, United States (enrolling)
• HaysMed — Hays, Kansas, United States (enrolling)

Full record on ClinicalTrials.gov

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