Recruiting

Phase 1

Phase 2

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

Sponsor:

National Cancer Institute (NCI)

Code:

NCT04172532

Conditions

Locally Advanced Pancreatic Adenocarcinoma

Stage III Pancreatic Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Computed Tomography

Hypofractionated Radiation Therapy

Magnetic Resonance Imaging

Study Details

Brief summary:

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.

Conditions

Locally Advanced Pancreatic Adenocarcinoma

Stage III Pancreatic Cancer AJCC v8

Study ID

NCT04172532

Start date

Jan 11, 2021

Status verified date

Jul, 2026

Completion date

Aug 1, 2027

Anticipated

Primary completion date

Aug 1, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female patients of childbearing potential and male patients must be willing to use an adequate method of contraception for the course of the study through 12 weeks after the last dose of study medication.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function. To be eligible for this trial, patients should be American Heart Association Stage B (people without current or previous symptoms of heart failure but with either structural heart disease, increased filling pressures in the heart or other risk factors) or better and New York Heart Association Functional Classification II (slight limitation of physical activity, comfortable at rest, ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain), or better
Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) and/or family member available will also be eligible

Exclusion Criteria:

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

Study Design

Enrollment

92 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase I (hypofractionated radiation therapy, M3814)

Patients in Phase I undergo hypofractionated radiation therapy for 5 fractions QOD over 2 weeks and receive M3814 PO QD for 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and tissue biopsy on study. Patients also undergo CT and MRI during screening and on study.

experimental: Phase II Group I (hypofractionated radiation therapy M3814)

Patients in Phase II undergo hypofractionated radiation therapy for 5 fractions QOD over 2 weeks and receive M3814 PO QD for 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and tissue biopsy on study. Patients also undergo CT and MRI during screening and on study.

placebo comparator: Phase II Group II(hypofractionated radiation therapy, placebo)

Patients in Phase II undergo hypofractionated radiation therapy for 5 fractions QOD over 2 weeks and receive placebo PO QD for 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and tissue biopsy on study. Patients also undergo CT and MRI during screening and on study.

Interventions

Biopsy Procedure

Undergo tissue collection

Biospecimen Collection

Undergo blood sample collection

Computed Tomography

Undergo CT

Hypofractionated Radiation Therapy

Undergo hypofractionated radiation therapy

Magnetic Resonance Imaging

Undergo MRI

Peposertib

Given PO

Placebo Administration

Given PO

Primary outcome measure

Maximum tolerated dose (Phase I) [ Time Frame: Up to 14 days ]
Recommended phase 2 dose (Phase I) [ Time Frame: Up to 14 days ]
Progression-free survival rate (Phase II) [ Time Frame: Time from randomization to progression or death whichever occurs first, assessed up to 2 years ]

Central Contacts and Locations

Locations

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

Contacts

Site Public Contact

800-826-4673 becomingapatient@coh.org

Principal Investigator:

Vincent Chung

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Recruiting

Irvine, California, United States, 92612

Contacts

Site Public Contact

877-827-8839 ucstudy@uci.edu

Principal Investigator:

Farshid Dayyani

City of Hope at Irvine Lennar

Recruiting

Irvine, California, United States, 92618

Contacts

Site Public Contact

877-467-3411

Principal Investigator:

Vincent Chung

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

877-827-8839 ucstudy@uci.edu

Principal Investigator:

Farshid Dayyani

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Site Public Contact

916-734-3089

Principal Investigator:

Edward J. Kim

UCHealth University of Colorado Hospital

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Site Public Contact

720-848-0650

Principal Investigator:

Sarah L. Davis

Sibley Memorial Hospital

Recruiting

Washington D.C., District of Columbia, United States, 20016

Contacts

Site Public Contact

202-243-2373 jquiver1@jhmi.edu

Principal Investigator:

Michael J. Pishvaian

University of Kansas Clinical Research Center

Recruiting

Fairway, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Anup K. Kasi Loknath Kumar

HaysMed

Recruiting

Hays, Kansas, United States, 67601

Contacts

Site Public Contact

785-623-5774

Principal Investigator:

Anup K. Kasi Loknath Kumar

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Anup K. Kasi Loknath Kumar

Lawrence Memorial Hospital

Recruiting

Lawrence, Kansas, United States, 66044

Contacts

Site Public Contact

785-505-2800 Stephanie.Norris@LMH.ORG

Principal Investigator:

Anup K. Kasi Loknath Kumar

The University of Kansas Cancer Center - Olathe

Recruiting

Olathe, Kansas, United States, 66061

Contacts

Site Public Contact

913-588-1569 OlatheCCResearch@kumc.edu

Principal Investigator:

Anup K. Kasi Loknath Kumar

University of Kansas Cancer Center-Overland Park

Recruiting

Overland Park, Kansas, United States, 66210

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Anup K. Kasi Loknath Kumar

Salina Regional Health Center

Recruiting

Salina, Kansas, United States, 67401

Contacts

Site Public Contact

785-452-7038 mleepers@srhc.com

Principal Investigator:

Anup K. Kasi Loknath Kumar

University of Kansas Health System Saint Francis Campus

Recruiting

Topeka, Kansas, United States, 66606

Contacts

Site Public Contact

785-295-8000

Principal Investigator:

Anup K. Kasi Loknath Kumar

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Anup K. Kasi Loknath Kumar

University Health Truman Medical Center

Recruiting

Kansas City, Missouri, United States, 64108

Contacts

Site Public Contact

816-404-4375

Principal Investigator:

Anup K. Kasi Loknath Kumar

University of Kansas Cancer Center - North

Recruiting

Kansas City, Missouri, United States, 64154

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Anup K. Kasi Loknath Kumar

University of Kansas Cancer Center - Lee's Summit

Recruiting

Lee's Summit, Missouri, United States, 64064

Contacts

Site Public Contact

913-588-3671 KUCC_Navigation@kumc.edu

Principal Investigator:

Anup K. Kasi Loknath Kumar

Cooperman Barnabas Medical Center

Recruiting

Livingston, New Jersey, United States, 07039

Contacts

Site Public Contact

973-322-5200

Principal Investigator:

Matthew P. Deek

Monmouth Medical Center

Recruiting

Long Branch, New Jersey, United States, 07740

Contacts

Site Public Contact

732-923-6564 mary.danish@rwjbh.org

Principal Investigator:

Matthew P. Deek

Rutgers Cancer Institute of New Jersey

Recruiting

New Brunswick, New Jersey, United States, 08903

Contacts

Site Public Contact

732-235-7356

Principal Investigator:

Matthew P. Deek

Mount Sinai Hospital

Recruiting

New York, New York, United States, 10029

Contacts

Site Public Contact

212-824-7309 CCTO@mssm.edu

Principal Investigator:

Karyn A. Goodman

NYP/Weill Cornell Medical Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-746-1848

Principal Investigator:

Allyson J. Ocean

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Janie Y. Zhang

VCU Massey Comprehensive Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Site Public Contact

804-628-6430 CTOclinops@vcu.edu

Principal Investigator:

Emma C. Fields

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Recruiting

Madison, Wisconsin, United States, 53718

Contacts

Site Public Contact

800-622-8922 clinicaltrials@cancer.wisc.edu

Principal Investigator:

Monica A. Patel

University of Wisconsin Carbone Cancer Center - University Hospital

Recruiting

Madison, Wisconsin, United States, 53792

Contacts

Site Public Contact

800-622-8922 clinicaltrials@cancer.wisc.edu

Principal Investigator:

Monica A. Patel

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 1, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-01.