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

NCT04172532 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2019-0764510366UM1CA186691
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 44

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

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (Phase I)

  Up to 14 days

• Recommended phase 2 dose (Phase I)

  Up to 14 days

• Progression-free survival rate (Phase II)

  The 95% confidence intervals will be provided.

  Time from randomization to progression or death whichever occurs first, assessed up to 2 years

Secondary Outcomes (6)

• Overall survival (OS)

  Time between the date of randomization and the date of patient death, assessed up to 2 years

• Two-year OS

  At 2 years

• Overall response rate

  Up to 2 years

• Disease control rate

  Up to 2 years

• Pharmacokinetic markers of M3814

  Up to 2 years

Other Outcomes (1)

• Gene signature of cell-free DNA from peripheral blood

  Baseline and after treatment

Study Arms (3)

Phase I (hypofractionated radiation therapy, M3814)

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Radiation: Hypofractionated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Drug: Peposertib

Phase II Group I (hypofractionated radiation therapy M3814)

EXPERIMENTAL

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Radiation: Hypofractionated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Drug: Peposertib

Phase II Group II(hypofractionated radiation therapy, placebo)

PLACEBO COMPARATOR

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.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Radiation: Hypofractionated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Other: Placebo Administration

Interventions

Biopsy Procedure PROCEDURE

Undergo tissue collection

Also known as: Biopsy, BIOPSY_TYPE, Bx

Phase I (hypofractionated radiation therapy, M3814); Phase II Group I (hypofractionated radiation therapy M3814); Phase II Group II(hypofractionated radiation therapy, placebo)

Hypofractionated Radiation Therapy RADIATION

Undergo hypofractionated radiation therapy

Also known as: Hypofractionated, Hypofractionated Radiotherapy, hypofractionation, Radiation, Hypofractionated

Phase I (hypofractionated radiation therapy, M3814); Phase II Group I (hypofractionated radiation therapy M3814); Phase II Group II(hypofractionated radiation therapy, placebo)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Phase I (hypofractionated radiation therapy, M3814); Phase II Group I (hypofractionated radiation therapy M3814); Phase II Group II(hypofractionated radiation therapy, placebo)

Peposertib DRUG

Given PO

Also known as: 3-Pyridazinemethanol, alpha-(2-Chloro-4-fluoro-5-(7-(4-morpholinyl)-4-quinazolinyl)phenyl)-6-methoxy-, (alphaS)-, M 3814, M-3814, M3814, MSC 2490484A, MSC-2490484A, MSC2490484A, Nedisertib

Phase I (hypofractionated radiation therapy, M3814); Phase II Group I (hypofractionated radiation therapy M3814)

Placebo Administration OTHER

Given PO

Phase II Group II(hypofractionated radiation therapy, placebo)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Phase I (hypofractionated radiation therapy, M3814); Phase II Group I (hypofractionated radiation therapy M3814); Phase II Group II(hypofractionated radiation therapy, placebo)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Phase I (hypofractionated radiation therapy, M3814); Phase II Group I (hypofractionated radiation therapy M3814); Phase II Group II(hypofractionated radiation therapy, placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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%)

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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (44)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

RECRUITING

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

Sibley Memorial Hospital

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

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

ACTIVE NOT RECRUITING

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

RECRUITING

HaysMed

Hays, Kansas, 67601, United States

RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

Lawrence Memorial Hospital

Lawrence, Kansas, 66044, United States

RECRUITING

The University of Kansas Cancer Center - Olathe

Olathe, Kansas, 66061, United States

RECRUITING

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, 66210, United States

RECRUITING

Mercy Hospital Pittsburg

Pittsburg, Kansas, 66762, United States

SUSPENDED

Salina Regional Health Center

Salina, Kansas, 67401, United States

RECRUITING

University of Kansas Health System Saint Francis Campus

Topeka, Kansas, 66606, United States

RECRUITING

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

WITHDRAWN

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

ACTIVE NOT RECRUITING

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

ACTIVE NOT RECRUITING

University Health Truman Medical Center

Kansas City, Missouri, 64108, United States

RECRUITING

University of Kansas Cancer Center - North

Kansas City, Missouri, 64154, United States

RECRUITING

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

RECRUITING

University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, 64116, United States

SUSPENDED

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

ACTIVE NOT RECRUITING

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

RECRUITING

Monmouth Medical Center

Long Branch, New Jersey, 07740, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

ACTIVE NOT RECRUITING

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

ACTIVE NOT RECRUITING

Mount Sinai Hospital

New York, New York, 10029, United States

RECRUITING

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

RECRUITING

Montefiore Medical Center-Einstein Campus

The Bronx, New York, 10461, United States

ACTIVE NOT RECRUITING

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

ACTIVE NOT RECRUITING

Wake Forest University at Clemmons

Clemmons, North Carolina, 27012, United States

ACTIVE NOT RECRUITING

Wake Forest Baptist Health - Wilkes Medical Center

Wilkesboro, North Carolina, 28659, United States

ACTIVE NOT RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

ACTIVE NOT RECRUITING

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Madison, Wisconsin, 53718, United States

RECRUITING

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Biopsy; Specimen Handling; Radiation Dose Hypofractionation; Radiation; Magnetic Resonance Spectroscopy; peposertib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Physical Phenomena; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Sarah L Davis

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2019
• First Posted: November 21, 2019
• Study Start: January 11, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (44)