RECRUITING

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

Conditions

Locally Advanced Pancreatic Adenocarcinoma Stage III Pancreatic Cancer AJCC v8

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 1/2 Study of M3814 (Peposertib) in Combination With Hypofractionated Radiotherapy for the Treatment of Locally Advanced Pancreatic Adenocarcinoma

Quick Facts

Study Start:2021-01-11

Study Completion:2026-08-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04172532

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patients must have pathologically confirmed pancreatic adenocarcinoma * Received 4-6 months of induction chemotherapy with fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX), fluorouracil, liposomal irinotecan, luecovorin, 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	* 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, CYP2CP, and CYP2C19. Concomitant use of CYP1A2, CYP2B6, and CYP3A4/5 substrates with a narrow therapeutic index are also excluded. Patients may confer with the study doctor to determine if alternative medications can be used. The following categories of medications and herbal supplements must be discontinued for at least the specified period of time before the patient can be treated: * Strong inducers of CYP3A4/5, CYP2C9 and CYP2C19: \>= 3 weeks prior to study treatment * Strong inhibitors of CYP3A4/5, CYP2C9 and CYP2C19: \>= 1 week prior to study treatment * Substrates of CYP1A2, CYP2B6, and CYP3A4/5 with a narrow therapeutic index: \>= 1 day prior to study treatment * 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 * 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

Inclusion Criteria

Exclusion Criteria

* Patients must have pathologically confirmed pancreatic adenocarcinoma
* Received 4-6 months of induction chemotherapy with fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX), fluorouracil, liposomal irinotecan, luecovorin, 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

* 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, CYP2CP, and CYP2C19. Concomitant use of CYP1A2, CYP2B6, and CYP3A4/5 substrates with a narrow therapeutic index are also excluded. Patients may confer with the study doctor to determine if alternative medications can be used. The following categories of medications and herbal supplements must be discontinued for at least the specified period of time before the patient can be treated:
* Strong inducers of CYP3A4/5, CYP2C9 and CYP2C19: \>= 3 weeks prior to study treatment
* Strong inhibitors of CYP3A4/5, CYP2C9 and CYP2C19: \>= 1 week prior to study treatment
* Substrates of CYP1A2, CYP2B6, and CYP3A4/5 with a narrow therapeutic index: \>= 1 day prior to study treatment
* 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
* 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

Contacts and Locations

Principal Investigator

Sarah L Davis

PRINCIPAL_INVESTIGATOR

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Study Locations (Sites)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010

United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612

United States

City of Hope at Irvine Lennar

Irvine, California, 92618

United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045

United States

Sibley Memorial Hospital

Washington, District of Columbia, 20016

United States

Northwestern University

Chicago, Illinois, 60611

United States

University of Kansas Clinical Research Center

Fairway, Kansas, 66205

United States

HaysMed

Hays, Kansas, 67601

United States

University of Kansas Cancer Center

Kansas City, Kansas, 66160

United States

Lawrence Memorial Hospital

Lawrence, Kansas, 66044

United States

The University of Kansas Cancer Center - Olathe

Olathe, Kansas, 66061

United States

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210

United States

Ascension Via Christi - Pittsburg

Pittsburg, Kansas, 66762

United States

Salina Regional Health Center

Salina, Kansas, 67401

United States

University of Kansas Health System Saint Francis Campus

Topeka, Kansas, 66606

United States

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205

United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536

United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334

United States

University Health Truman Medical Center

Kansas City, Missouri, 64108

United States

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154

United States

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064

United States

University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, 64116

United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756

United States

Saint Barnabas Medical Center

Livingston, New Jersey, 07039

United States

Monmouth Medical Center

Long Branch, New Jersey, 07740

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903

United States

Montefiore Medical Center-Einstein Campus

Bronx, New York, 10461

United States

Montefiore Medical Center - Moses Campus

Bronx, New York, 10467

United States

Roswell Park Cancer Institute

Buffalo, New York, 14263

United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016

United States

Mount Sinai Hospital

New York, New York, 10029

United States

NYP/Weill Cornell Medical Center

New York, New York, 10065

United States

Wake Forest University at Clemmons

Clemmons, North Carolina, 27012

United States

Wake Forest Baptist Health - Wilkes Medical Center

Wilkesboro, North Carolina, 28659

United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157

United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112

United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Sarah L Davis, PRINCIPAL_INVESTIGATOR, JHU Sidney Kimmel Comprehensive Cancer Center LAO

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-01-11

Study Completion Date2026-08-01

Study Record Updates

Study Start Date2021-01-11

Study Completion Date2026-08-01

Terms related to this study

Additional Relevant MeSH Terms

Locally Advanced Pancreatic Adenocarcinoma
Stage III Pancreatic Cancer AJCC v8