Testing the Addition of the Immunotherapy Drug, Pembrolizumab, to the Usual Radiation Treatment for Newly Diagnosed Early Stage High Intermediate Risk Endometrial Cancer

March 5, 2024 updated by: National Cancer Institute (NCI)

A Phase III Randomized Trial of Radiation +/- Pembrolizumab (MK-3475) for Newly Diagnosed Early Stage High Intermediate Risk Mismatch Repair Deficient (dMMR) Endometrioid Endometrial Cancer

This phase III trial compares whether the addition of pembrolizumab to radiation therapy is more effective than radiation therapy alone in reducing the risk of cancer coming back (recurrence) in patients with newly diagnosed stage I-II endometrial cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. The addition of pembrolizumab to radiation treatment may be more effective than radiation treatment alone in reducing cancer recurrence.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To compare the 3-year recurrence-free survival of women with high intermediate risk (HIR) stage I/II mismatch repair deficient (dMMR) endometrioid endometrial cancer treated with radiation and pembrolizumab (MK-3475) versus radiation alone.

SECONDARY OBJECTIVES:

I. To describe the safety and tolerability of concurrent pembrolizumab (MK-3475) and radiation compared to radiation alone in patients with MMR deficient high intermediate risk endometrial cancer (HIR EC).

II. To describe the recurrence patterns in each group. III. To measure recurrence free survival at 5 years in each group. IV. To estimate disease specific overall survival in each group. V. To determine whether the addition of pembrolizumab (MK-3475) to radiation, compared with radiation alone is associated with decreased quality of life at 6- and 24-weeks, as measured with the Functional Assessment of Cancer Therapy (FACT)-Endometrial (En) Trial Outcome Index (TOI), increased gastrointestinal (GI) symptoms as measured with the GI subscale, and increased fatigue as measured with the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue scale (short form).

VI. To validate the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM) subscale, which assesses in cancer patients on immunotherapy.

VII. To evaluate the ability of ctDNA to predict outcomes in the experimental and control groups.

CORRELATIVE/TERTIARY OBJECTIVES:

I. To explore the baseline tumor genetic and microenvironment parameters predictive of clinical benefit or resistance to immunotherapy.

II. To determine whether the addition of pembrolizumab (MK-3475) to radiation, compared with radiation alone, is associated with decreased quality of life as measured with the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM subscale) and more self-reported bother from side effects as measured with a single item GP5 "I am bothered by side effects," a question from the FACT-En TOI.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo pelvic external beam radiation therapy (EBRT) daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity.

Patients in both arms also undergo collection of blood samples and computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, or x-ray imaging throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Type

Interventional

Enrollment (Estimated)

168

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • Bayamon, Puerto Rico, 00959-5060
        • Cancer Center-Metro Medical Center Bayamon
      • Manati, Puerto Rico, 00674
        • Doctors Cancer Center
      • San Juan, Puerto Rico, 00917
        • San Juan Community Oncology Group
      • San Juan, Puerto Rico, 00927
        • Centro Comprensivo de Cancer de UPR
      • San Juan, Puerto Rico, 00936
        • San Juan City Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
    • California
      • Clovis, California, United States, 93611
        • Community Cancer Institute
      • Clovis, California, United States, 93611
        • University Oncology Associates
      • Concord, California, United States, 94520
        • John Muir Medical Center-Concord Campus
      • La Jolla, California, United States, 92093
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90095
        • UCLA / Jonsson Comprehensive Cancer Center
      • Los Angeles, California, United States, 90033
        • Los Angeles General Medical Center
      • San Francisco, California, United States, 94158
        • UCSF Medical Center-Mission Bay
      • Walnut Creek, California, United States, 94598
        • John Muir Medical Center-Walnut Creek
    • Colorado
      • Aurora, Colorado, United States, 80045
        • UCHealth University of Colorado Hospital
      • Colorado Springs, Colorado, United States, 80909
        • UCHealth Memorial Hospital Central
      • Colorado Springs, Colorado, United States, 80907
        • Rocky Mountain Cancer Centers-Penrose
      • Colorado Springs, Colorado, United States, 80920
        • Memorial Hospital North
      • Denver, Colorado, United States, 80210
        • Porter Adventist Hospital
      • Highlands Ranch, Colorado, United States, 80129
        • UCHealth Highlands Ranch Hospital
      • Littleton, Colorado, United States, 80122
        • Littleton Adventist Hospital
      • Parker, Colorado, United States, 80138
        • Parker Adventist Hospital
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • Danbury Hospital
      • Derby, Connecticut, United States, 06418
        • Smilow Cancer Hospital-Derby Care Center
      • Fairfield, Connecticut, United States, 06824
        • Smilow Cancer Hospital Care Center-Fairfield
      • Glastonbury, Connecticut, United States, 06033
        • Smilow Cancer Hospital Care Center at Glastonbury
      • Greenwich, Connecticut, United States, 06830
        • Smilow Cancer Hospital Care Center at Greenwich
      • Guilford, Connecticut, United States, 06437
        • Smilow Cancer Hospital Care Center - Guilford
      • Hartford, Connecticut, United States, 06105
        • Smilow Cancer Hospital Care Center at Saint Francis
      • New Haven, Connecticut, United States, 06520
        • Yale University
      • New Haven, Connecticut, United States, 06510
        • Smilow Cancer Center/Yale-New Haven Hospital
      • North Haven, Connecticut, United States, 06473
        • Yale-New Haven Hospital North Haven Medical Center
      • Norwalk, Connecticut, United States, 06856
        • Norwalk Hospital
      • Orange, Connecticut, United States, 06477
        • Smilow Cancer Hospital-Orange Care Center
      • Torrington, Connecticut, United States, 06790
        • Smilow Cancer Hospital-Torrington Care Center
      • Trumbull, Connecticut, United States, 06611
        • Smilow Cancer Hospital Care Center-Trumbull
      • Waterbury, Connecticut, United States, 06708
        • Smilow Cancer Hospital-Waterbury Care Center
      • Waterford, Connecticut, United States, 06385
        • Smilow Cancer Hospital Care Center - Waterford
    • Florida
      • Fort Myers, Florida, United States, 33905
        • Regional Cancer Center-Lee Memorial Health System
      • Fort Myers, Florida, United States, 33905
        • Florida Gynecologic Oncology
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
      • Cumming, Georgia, United States, 30041
        • Northside Hospital-Forsyth
      • Marietta, Georgia, United States, 30060
        • WellStar Kennestone Hospital
      • Newnan, Georgia, United States, 30265
        • CTCA at Southeastern Regional Medical Center
      • Savannah, Georgia, United States, 31405
        • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
      • Savannah, Georgia, United States, 31404
        • Memorial Health University Medical Center
    • Hawaii
      • 'Aiea, Hawaii, United States, 96701
        • Pali Momi Medical Center
      • 'Aiea, Hawaii, United States, 96701
        • Hawaii Cancer Care - Westridge
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
      • Honolulu, Hawaii, United States, 96817
        • The Cancer Center of Hawaii-Liliha
      • Honolulu, Hawaii, United States, 96813
        • Hawaii Cancer Care Inc - Waterfront Plaza
      • Honolulu, Hawaii, United States, 96813
        • Queen's Cancer Cenrer - POB I
      • Honolulu, Hawaii, United States, 96813
        • Straub Clinic and Hospital
      • Honolulu, Hawaii, United States, 96813
        • University of Hawaii Cancer Center
      • Honolulu, Hawaii, United States, 96817
        • Hawaii Cancer Care Inc-Liliha
      • Honolulu, Hawaii, United States, 96817
        • Queen's Cancer Center - Kuakini
      • Honolulu, Hawaii, United States, 96826
        • Kapiolani Medical Center for Women and Children
      • Lihue, Hawaii, United States, 96766
        • Wilcox Memorial Hospital and Kauai Medical Clinic
    • Idaho
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
      • Fruitland, Idaho, United States, 83619
        • Saint Luke's Cancer Institute - Fruitland
      • Meridian, Idaho, United States, 83642
        • Saint Luke's Cancer Institute - Meridian
      • Nampa, Idaho, United States, 83686
        • Saint Luke's Cancer Institute - Nampa
      • Twin Falls, Idaho, United States, 83301
        • Saint Luke's Cancer Institute - Twin Falls
    • Illinois
      • Centralia, Illinois, United States, 62801
        • Centralia Oncology Clinic
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago Comprehensive Cancer Center
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Decatur, Illinois, United States, 62526
        • Cancer Care Specialists of Illinois - Decatur
      • Effingham, Illinois, United States, 62401
        • Crossroads Cancer Center
      • Evanston, Illinois, United States, 60201
        • NorthShore University HealthSystem-Evanston Hospital
      • Geneva, Illinois, United States, 60134
        • Northwestern Medicine Cancer Center Delnor
      • Glenview, Illinois, United States, 60026
        • NorthShore University HealthSystem-Glenbrook Hospital
      • Highland Park, Illinois, United States, 60035
        • NorthShore University HealthSystem-Highland Park Hospital
      • Lake Forest, Illinois, United States, 60045
        • Northwestern Medicine Lake Forest Hospital
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • New Lenox, Illinois, United States, 60451
        • UC Comprehensive Cancer Center at Silver Cross
      • O'Fallon, Illinois, United States, 62269
        • Cancer Care Center of O'Fallon
      • Orland Park, Illinois, United States, 60462
        • University of Chicago Medicine-Orland Park
      • Springfield, Illinois, United States, 62781
        • Memorial Medical Center
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University School of Medicine
      • Springfield, Illinois, United States, 62702
        • Springfield Clinic
      • Warrenville, Illinois, United States, 60555
        • Northwestern Medicine Cancer Center Warrenville
      • Zion, Illinois, United States, 60099
        • Midwestern Regional Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • Ascension Saint Vincent Indianapolis Hospital
    • Iowa
      • Ames, Iowa, United States, 50010
        • Mary Greeley Medical Center
      • Ames, Iowa, United States, 50010
        • McFarland Clinic - Ames
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Kentucky
      • Edgewood, Kentucky, United States, 41017
        • Saint Elizabeth Healthcare Edgewood
      • Lexington, Kentucky, United States, 40503
        • Baptist Health Lexington
      • Louisville, Kentucky, United States, 40207
        • Baptist Health Louisville
    • Louisiana
      • Metairie, Louisiana, United States, 70006
        • East Jefferson General Hospital
      • New Orleans, Louisiana, United States, 70112
        • University Medical Center New Orleans
      • New Orleans, Louisiana, United States, 70112
        • Louisiana State University Health Science Center
    • Maine
      • Bath, Maine, United States, 04530
        • MaineHealth Coastal Cancer Treatment Center
      • Biddeford, Maine, United States, 04005
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
      • Portland, Maine, United States, 04102
        • Maine Medical Center-Bramhall Campus
      • Sanford, Maine, United States, 04073
        • MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
      • Scarborough, Maine, United States, 04074
        • Maine Medical Center- Scarborough Campus
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Sinai Hospital of Baltimore
    • Michigan
      • Dearborn, Michigan, United States, 48124
        • Beaumont Hospital - Dearborn
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont Hospital-Royal Oak
      • Troy, Michigan, United States, 48085
        • William Beaumont Hospital - Troy
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Minnesota Oncology - Burnsville
      • Coon Rapids, Minnesota, United States, 55433
        • Mercy Hospital
      • Edina, Minnesota, United States, 55435
        • Fairview Southdale Hospital
      • Fridley, Minnesota, United States, 55432
        • Unity Hospital
      • Maplewood, Minnesota, United States, 55109
        • Minnesota Oncology Hematology PA-Maplewood
      • Minneapolis, Minnesota, United States, 55407
        • Abbott-Northwestern Hospital
      • Monticello, Minnesota, United States, 55362
        • Monticello Cancer Center
      • Saint Cloud, Minnesota, United States, 56303
        • Coborn Cancer Center at Saint Cloud Hospital
      • Saint Louis Park, Minnesota, United States, 55416
        • Park Nicollet Clinic - Saint Louis Park
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
      • Waconia, Minnesota, United States, 55387
        • Ridgeview Medical Center
      • Willmar, Minnesota, United States, 56201
        • Rice Memorial Hospital
      • Woodbury, Minnesota, United States, 55125
        • Minnesota Oncology Hematology PA-Woodbury
    • Missouri
      • Farmington, Missouri, United States, 63640
        • Parkland Health Center - Farmington
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
      • Saint Louis, Missouri, United States, 63131
        • Missouri Baptist Medical Center
      • Saint Louis, Missouri, United States, 63141
        • Mercy Hospital Saint Louis
      • Saint Louis, Missouri, United States, 63128
        • Mercy Hospital South
      • Sainte Genevieve, Missouri, United States, 63670
        • Sainte Genevieve County Memorial Hospital
      • Springfield, Missouri, United States, 65807
        • CoxHealth South Hospital
      • Springfield, Missouri, United States, 65804
        • Mercy Hospital Springfield
      • Sullivan, Missouri, United States, 63080
        • Missouri Baptist Sullivan Hospital
      • Sunset Hills, Missouri, United States, 63127
        • BJC Outpatient Center at Sunset Hills
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic Cancer Center
      • Bozeman, Montana, United States, 59715
        • Bozeman Deaconess Hospital
      • Missoula, Montana, United States, 59804
        • Community Medical Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital
      • Omaha, Nebraska, United States, 68124
        • Alegent Health Bergan Mercy Medical Center
      • Omaha, Nebraska, United States, 68114
        • Oncology Associates PC
      • Omaha, Nebraska, United States, 68114
        • Nebraska Cancer Specialists/Oncology Hematology West PC - MECC
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Women's Cancer Center of Nevada
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering Basking Ridge
      • Camden, New Jersey, United States, 08103
        • Cooper Hospital University Medical Center
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Monmouth
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Bergen
      • Moorestown, New Jersey, United States, 08057
        • Virtua Samson Cancer Center
      • Neptune, New Jersey, United States, 07753
        • Jersey Shore Medical Center
      • Voorhees, New Jersey, United States, 08043
        • Virtua Voorhees
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • University of New Mexico Cancer Center
    • New York
      • Albany, New York, United States, 12208
        • Women's Cancer Care Associates LLC
      • Brooklyn, New York, United States, 11215
        • New York-Presbyterian/Brooklyn Methodist Hospital
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Commack
      • Flushing, New York, United States, 11355
        • The New York Hospital Medical Center of Queens
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Westchester
      • Lake Success, New York, United States, 11042
        • Northwell Health/Center for Advanced Medicine
      • Mineola, New York, United States, 11501
        • NYU Winthrop Hospital
      • New Hyde Park, New York, United States, 11040
        • Long Island Jewish Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10019
        • Mount Sinai West
      • New York, New York, United States, 10029
        • Mount Sinai Hospital
      • New York, New York, United States, 10065
        • NYP/Weill Cornell Medical Center
      • New York, New York, United States, 10011
        • Mount Sinai Chelsea
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Rochester, New York, United States, 14620
        • Highland Hospital
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Medical Center
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Nassau
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Greensboro, North Carolina, United States, 27403
        • Cone Health Cancer Center
      • Raleigh, North Carolina, United States, 27609
        • Duke Raleigh Hospital
      • Raleigh, North Carolina, United States, 27607
        • Duke Women's Cancer Care Raleigh
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Roger Maris Cancer Center
      • Fargo, North Dakota, United States, 58122
        • Sanford Broadway Medical Center
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • UHHS-Chagrin Highlands Medical Center
      • Canton, Ohio, United States, 44710
        • Aultman Health Foundation
      • Centerville, Ohio, United States, 45459
        • Miami Valley Hospital South
      • Centerville, Ohio, United States, 45459
        • Dayton Physicians LLC-Miami Valley South
      • Chardon, Ohio, United States, 44024
        • Geauga Hospital
      • Cincinnati, Ohio, United States, 45220
        • Good Samaritan Hospital - Cincinnati
      • Cincinnati, Ohio, United States, 45242
        • Bethesda North Hospital
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44111
        • Cleveland Clinic Cancer Center/Fairview Hospital
      • Columbus, Ohio, United States, 43214
        • Riverside Methodist Hospital
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Columbus, Ohio, United States, 43219
        • The Mark H Zangmeister Center
      • Columbus, Ohio, United States, 43213
        • Mount Carmel East Hospital
      • Columbus, Ohio, United States, 43222
        • Mount Carmel Health Center West
      • Dayton, Ohio, United States, 45415
        • Dayton Physician LLC-Miami Valley Hospital North
      • Dayton, Ohio, United States, 45415
        • Miami Valley Hospital North
      • Dublin, Ohio, United States, 43016
        • Dublin Methodist Hospital
      • Franklin, Ohio, United States, 45005-1066
        • Atrium Medical Center-Middletown Regional Hospital
      • Franklin, Ohio, United States, 45005
        • Dayton Physicians LLC-Atrium
      • Grove City, Ohio, United States, 43123
        • Mount Carmel Grove City Hospital
      • Mayfield Heights, Ohio, United States, 44124
        • Hillcrest Hospital Cancer Center
      • Mentor, Ohio, United States, 44060
        • UH Seidman Cancer Center at Lake Health Mentor Campus
      • New Albany, Ohio, United States, 43054
        • Mount Carmel New Albany Surgical Hospital
      • Wadsworth, Ohio, United States, 44281
        • University Hospitals Sharon Health Center
      • Westerville, Ohio, United States, 43081
        • Saint Ann's Hospital
      • Westlake, Ohio, United States, 44145
        • UH Seidman Cancer Center at Saint John Medical Center
      • Westlake, Ohio, United States, 44145
        • UHHS-Westlake Medical Center
      • Zanesville, Ohio, United States, 43701
        • Genesis Healthcare System Cancer Care Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
      • Oklahoma City, Oklahoma, United States, 73120
        • Mercy Hospital Oklahoma City
    • Oregon
      • Clackamas, Oregon, United States, 97015
        • Clackamas Radiation Oncology Center
      • Clackamas, Oregon, United States, 97015
        • Providence Cancer Institute Clackamas Clinic
      • Gresham, Oregon, United States, 97030
        • Legacy Mount Hood Medical Center
      • Newberg, Oregon, United States, 97132
        • Providence Newberg Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital and Medical Center
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • Providence Saint Vincent Medical Center
      • Tualatin, Oregon, United States, 97062
        • Legacy Meridian Park Hospital
    • Pennsylvania
      • Carlisle, Pennsylvania, United States, 17015
        • Carlisle Regional Cancer Center
      • Ephrata, Pennsylvania, United States, 17522
        • Ephrata Cancer Center
      • Gettysburg, Pennsylvania, United States, 17325
        • Adams Cancer Center
      • Greensburg, Pennsylvania, United States, 15601
        • UPMC Cancer Centers - Arnold Palmer Pavilion
      • Harrisburg, Pennsylvania, United States, 17109
        • UPMC Pinnacle Cancer Center/Community Osteopathic Campus
      • Lancaster, Pennsylvania, United States, 17601
        • Lancaster General Ann B Barshinger Cancer Institute
      • Lancaster, Pennsylvania, United States, 17602
        • Lancaster General Hospital
      • Lebanon, Pennsylvania, United States, 17042
        • Sechler Family Cancer Center
      • Mechanicsburg, Pennsylvania, United States, 17050
        • UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
      • Paoli, Pennsylvania, United States, 19301
        • Paoli Memorial Hospital
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania/Abramson Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Pennsylvania Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC-Magee Womens Hospital
      • West Chester, Pennsylvania, United States, 19380
        • Chester County Hospital
      • Willow Grove, Pennsylvania, United States, 19090
        • Asplundh Cancer Pavilion
      • Wynnewood, Pennsylvania, United States, 19096
        • Lankenau Medical Center
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Cancer Center
      • York, Pennsylvania, United States, 17403
        • WellSpan Health-York Hospital
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Women and Infants Hospital
      • Westerly, Rhode Island, United States, 02891
        • Smilow Cancer Hospital Care Center - Westerly
    • South Carolina
      • Bluffton, South Carolina, United States, 29910
        • Saint Joseph's/Candler - Bluffton Campus
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Cancer Institute - Faris
      • Greenville, South Carolina, United States, 29607
        • Saint Francis Cancer Center
      • Greenville, South Carolina, United States, 29601
        • Saint Francis Hospital
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
      • Sioux Falls, South Dakota, United States, 57117-5134
        • Sanford USD Medical Center - Sioux Falls
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center Oncology Clinic
    • Texas
      • Conroe, Texas, United States, 77384
        • MD Anderson in The Woodlands
      • Dallas, Texas, United States, 75235
        • Parkland Memorial Hospital
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
      • Houston, Texas, United States, 77070
        • Methodist Willowbrook Hospital
      • Houston, Texas, United States, 77030
        • Ben Taub General Hospital
      • Houston, Texas, United States, 77094
        • Houston Methodist West Hospital
      • Houston, Texas, United States, 77079
        • MD Anderson West Houston
      • League City, Texas, United States, 77573
        • MD Anderson League City
      • Sugar Land, Texas, United States, 77478
        • MD Anderson in Sugar Land
      • Sugar Land, Texas, United States, 77479
        • Houston Methodist Sugar Land Hospital
      • The Woodlands, Texas, United States, 77385
        • Houston Methodist The Woodlands Hospital
    • Utah
      • Farmington, Utah, United States, 84025
        • Farmington Health Center
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute/University of Utah
      • Salt Lake City, Utah, United States, 84106
        • University of Utah Sugarhouse Health Center
    • Virginia
      • Richmond, Virginia, United States, 23235
        • VCU Massey Cancer Center at Stony Point
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University/Massey Cancer Center
      • Roanoke, Virginia, United States, 24016
        • Carilion Clinic Gynecological Oncology
    • Washington
      • Vancouver, Washington, United States, 98686
        • Legacy Salmon Creek Hospital
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • West Virginia University Charleston Division
    • Wisconsin
      • Brookfield, Wisconsin, United States, 53045
        • Ascension Southeast Wisconsin Hospital - Elmbrook Campus
      • Eau Claire, Wisconsin, United States, 54701
        • Marshfield Medical Center-EC Cancer Center
      • Franklin, Wisconsin, United States, 53132
        • Ascension Saint Francis - Reiman Cancer Center
      • Franklin, Wisconsin, United States, 53132
        • Ascension Southeast Wisconsin Hospital - Franklin
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Mequon, Wisconsin, United States, 53097
        • Ascension Columbia Saint Mary's Hospital Ozaukee
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Milwaukee, Wisconsin, United States, 53210
        • Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
      • Milwaukee, Wisconsin, United States, 53211
        • Ascension Columbia Saint Mary's Hospital - Milwaukee
      • Milwaukee, Wisconsin, United States, 53215
        • Ascension Saint Francis Hospital
      • Minocqua, Wisconsin, United States, 54548
        • Marshfield Clinic-Minocqua Center
      • Racine, Wisconsin, United States, 53405
        • Ascension All Saints Hospital
      • Rice Lake, Wisconsin, United States, 54868
        • Marshfield Medical Center-Rice Lake
      • Stevens Point, Wisconsin, United States, 54482
        • Marshfield Medical Center-River Region at Stevens Point
      • Wauwatosa, Wisconsin, United States, 53226
        • Ascension Medical Group Southeast Wisconsin - Mayfair Road
      • Weston, Wisconsin, United States, 54476
        • Marshfield Medical Center - Weston

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have:

    • Stage I endometrioid endometrial cancer and a combination of age and risk factors as listed below:

      • Age >= 70 and 1 or more risk factors
      • Age 50 - < 70 and 2 or more risk factors

      • Age < 50 and 3 risk factors

        • Risk factors:

          • Myometrial invasion >= 50%
          • Lymphovascular space invasion
          • Grade 2 or 3 OR

    • Stage II endometrioid endometrial cancer

      • Note: Patients with isolated tumor cells in sentinel lymph nodes are eligible (considered N0i) as long as there is no evidence of micro- or macro-metastases in any lymph nodes
  • CT or MRI abdomen or pelvis and either chest X-ray or CT chest demonstrating no evidence of disease outside of the uterus. Imaging can be performed pre-operatively or post-operatively. CT with contrast is the preferred modality. Positron emission tomography (PET)/CT is NOT to be used for any disease assessment or reassessment unless there is documentation that PET/CT is of diagnostic quality equal to CT with contrast
  • Patients must have deficient mismatch repair as demonstrated by lack of expression of at least one mismatch repair protein by immunohistochemistry (IHC) and/or evidence of microsatellite instability (MSI) high. The institutional pathology report documenting MMR deficiency must be submitted
  • Patients must have undergone surgical staging with at least hysterectomy, removal of cervix, bilateral (if both are present) salpingo-oophorectomy, and either sentinel lymph node assessment or complete pelvic +/- aortic lymphadenectomy. Secondary staging is allowed to determine stage. Patients with isolated tumor cells in sentinel lymph nodes are eligible (considered N0i) as long as there is no evidence of micro- or macro-metastases in any lymph nodes
  • Patients must have received no prior therapy for endometrial cancer, including hormonal therapy, chemotherapy, targeted therapy, immunotherapy or radiation therapy
  • Age >= 18
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Platelets >= 100,000/mcl (within 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1,500/mcl (within 14 days prior to registration)
  • Creatinine =< 1.5 x laboratory upper limit of normal (ULN) (within 14 days prior to registration)
  • Bilirubin =< 1.5 x ULN (within 14 days prior to registration) (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN (within 14 days prior to registration)
  • Thyroid stimulating hormone (TSH) within normal limits (TSH < ULN allowed in euthyroid patients on thyroid replacement therapy)
  • Patients must be registered between 1 and 8 weeks after initial (staging) surgery performed for the combined purpose of diagnosis and staging
  • Human immunodeficiency virus (HIV) testing is not required by protocol unless clinically indicated. Known HIV positive patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

  • Patients who are currently participating and receiving cancer-directed study therapy for endometrial cancer or have participated in a study of an investigational agent and received cancer-directed study therapy for endometrial cancer within 4 weeks prior to registration
  • Patients who have received prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapeutic antibody or other similar agents
  • Patients who have a history of a severe hypersensitivity reaction to monoclonal antibody or MK-3475 (pembrolizumab) and/or its excipients
  • Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. This includes, but is not limited to, patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
  • Patients with a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis

  • Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to registration:

    • Patients who have received steroids as CT scan contrast premedication may be enrolled
    • The use of inhaled or topical corticosteroids is allowed
    • The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
    • The use of physiologic doses of corticosteroids may be approved after consultation with the study chair (e.g. 10 mg of prednisone used for replacement therapy for adrenal insufficiency)
  • Patients who are lactating
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis. 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
  • Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection (except for uncomplicated urinary tract infection), interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients who have received any of the prohibited medications

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm I (EBRT, brachytherapy)
Patients undergo pelvic EBRT daily for 5-6 weeks and vaginal brachytherapy completed within 7 days after completion of EBRT in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • EBRT
  • Definitive Radiation Therapy
  • External Beam Radiation
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
  • Radiation, External Beam
  • Teleradiotherapy
  • Teletherapy
  • Teletherapy Radiation
  • External Beam Radiotherapy (conventional)
Procedure: X-Ray Imaging
Undergo x-rays
Other Names:
  • Conventional X-Ray
  • Diagnostic Radiology
  • Medical Imaging, X-Ray
  • Radiographic Imaging
  • Radiography
  • RG
  • Static X-Ray
  • X-Ray
  • Plain film radiographs
  • Radiographic imaging procedure (procedure)
Radiation: Brachytherapy
Undergo vaginal brachytherapy
Other Names:
  • Brachytherapy, NOS
  • Internal Radiation
  • Internal Radiation Brachytherapy
  • Internal Radiation Therapy
  • Radiation Brachytherapy
  • Radiation, Internal
Experimental: Arm II (EBRT, brachytherapy, pembrolizumab)
Patients undergo EBRT and brachytherapy as in Arm I. Within 7 days prior to the start of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 6 weeks for up to 1 year (9 cycles) in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and CT scans, MRI scans, or x-ray imaging throughout the trial.
Other: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Procedure: Biospecimen Collection
Undergo collection of blood
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Biological: Pembrolizumab
Given IV
Other Names:
  • Keytruda
  • MK-3475
  • Lambrolizumab
  • SCH 900475
  • BCD-201
  • Pembrolizumab Biosimilar BCD-201
Radiation: External Beam Radiation Therapy
Undergo EBRT
Other Names:
  • EBRT
  • Definitive Radiation Therapy
  • External Beam Radiation
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
  • Radiation, External Beam
  • Teleradiotherapy
  • Teletherapy
  • Teletherapy Radiation
  • External Beam Radiotherapy (conventional)
Procedure: X-Ray Imaging
Undergo x-rays
Other Names:
  • Conventional X-Ray
  • Diagnostic Radiology
  • Medical Imaging, X-Ray
  • Radiographic Imaging
  • Radiography
  • RG
  • Static X-Ray
  • X-Ray
  • Plain film radiographs
  • Radiographic imaging procedure (procedure)
Radiation: Brachytherapy
Undergo vaginal brachytherapy
Other Names:
  • Brachytherapy, NOS
  • Internal Radiation
  • Internal Radiation Brachytherapy
  • Internal Radiation Therapy
  • Radiation Brachytherapy
  • Radiation, Internal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3 year recurrence-free survival
Time Frame: Time from study entry (randomization) to the time of cancer recurrence, assessed at 3 years
Will be estimated using the Kaplan Meier method and treatment comparisons will be made using a stratified log-rank test.
Time from study entry (randomization) to the time of cancer recurrence, assessed at 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: 12 months
Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) by treatment regimen. Will be evaluated descriptively using frequencies and percentages and will be reported using tables. Differences between treatment arms will be assessed through absolute deviations and contingency table analyses. All patients who receive treatment, will be evaluated for toxicity. Toxicities by type and maximum grade over the course of treatment and follow up will be summarized and by date of occurrence (acute toxicity and late adverse effects).
12 months
Recurrence patterns
Time Frame: 5 years
The cumulative incidences of vaginal recurrence, pelvic recurrence, retroperitoneal, and distant recurrence from endometrial cancer will be estimated within treatment regimen. Treatments will be compared graphically using Kaplan-Meier estimates of the survival function.
5 years
5 year recurrence free survival
Time Frame: Time from study entry (randomization) to the time of cancer recurrence, assessed at 5 years
Proportions will be compared by treatment using Fisher's exact test. This analysis may be delayed until the data are mature.
Time from study entry (randomization) to the time of cancer recurrence, assessed at 5 years
Overall survival
Time Frame: Duration of time from study entry to time of death or the date of last contact, assessed up to 5 years
Will be estimated using the Kaplan Meier method and treatment comparisons will be made using a stratified log-rank test.
Duration of time from study entry to time of death or the date of last contact, assessed up to 5 years
Patient-reported outcomes
Time Frame: Up to 2 years after starting treatment
Will be assessed by questionnaire.
Up to 2 years after starting treatment
Impact of circulating tumor deoxyribonucleic acid (ctDNA) on treatment outcomes
Time Frame: Up to 5 years
Will examine the association between ctDNA and 2- year (or 3-year) progression free survival in a 2-stages of analysis.
Up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Potential transformations of the severity of adverse events
Time Frame: 12 months
An example of potential transformation of the severity of adverse events is whether or not the patient experienced >= grade 3 events. It will be assessed by CTCAE and treatment regimen.
12 months
Biomarker analysis
Time Frame: Baseline
Will assess baseline genetic characteristics (e.g. mutations) and microenvironment parameters, treatment, and interactions between treatment and biomarkers in a Cox regression.
Baseline
Functional Assessment of Cancer Therapy (FACT)-Immune Checkpoint Modulator (ICM) subscale
Time Frame: Up to 2 years after starting treatment
Treatment differences in the FACT-ICM subscale and self-reported bother from side effects will be explored using a linear mixed model for repeated measures, adjusted for the baseline score.
Up to 2 years after starting treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Collaborators

NRG Oncology

Investigators

  • Principal Investigator: Floor Backes, NRG Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start (Actual)

April 9, 2020

Primary Completion (Estimated)

February 1, 2025

Study Completion (Estimated)

February 1, 2025

Study Registration Dates

First Submitted

December 27, 2019

First Submitted That Met QC Criteria

December 27, 2019

First Posted (Actual)

December 30, 2019

Study Record Updates

Last Update Posted (Estimated)

March 6, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2019-08602 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180868 (U.S. NIH Grant/Contract)
  • NRG-GY020 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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