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

Endometrial Endometrioid Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04214067
• Other study ID #: NCI-2019-08602
• Secondary ID: NCI-2019-08602NR
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 9, 2020
• Est. completion date: February 1, 2025

Study information

• Verified date: February 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 168
• Est. completion date: February 1, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Endometrioid
• Endometrial Endometrioid Adenocarcinoma
• Endometrial Neoplasms
• Stage I Uterine Corpus Cancer AJCC v8
• Stage II Uterine Corpus Cancer AJCC v8

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood

Radiation:
• Brachytherapy
Undergo vaginal brachytherapy

Procedure:
• Computed Tomography
Undergo CT

Radiation:
• External Beam Radiation Therapy
Undergo EBRT

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Biological:
• Pembrolizumab
Given IV

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Procedure:
• X-Ray Imaging
Undergo x-rays

Locations

Country	Name	City	State
Puerto Rico	Cancer Center-Metro Medical Center Bayamon	Bayamon
Puerto Rico	Doctors Cancer Center	Manati
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	San Juan Community Oncology Group	San Juan
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Women's Cancer Care Associates LLC	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Northside Hospital	Atlanta	Georgia
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	MaineHealth Coastal Cancer Treatment Center	Bath	Maine
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Saint Joseph's/Candler - Bluffton Campus	Bluffton	South Carolina
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Ascension Southeast Wisconsin Hospital - Elmbrook Campus	Brookfield	Wisconsin
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Aultman Health Foundation	Canton	Ohio
United States	Carlisle Regional Cancer Center	Carlisle	Pennsylvania
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Geauga Hospital	Chardon	Ohio
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Community Cancer Institute	Clovis	California
United States	University Oncology Associates	Clovis	California
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	John Muir Medical Center-Concord	Concord	California
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Northside Hospital-Forsyth	Cumming	Georgia
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Danbury Hospital	Danbury	Connecticut
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Dublin Methodist Hospital	Dublin	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Farmington Health Center	Farmington	Utah
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	The New York Hospital Medical Center of Queens	Flushing	New York
United States	GenesisCare USA - FGO	Fort Myers	Florida
United States	Regional Cancer Center-Lee Memorial Health System	Fort Myers	Florida
United States	Ascension Saint Francis - Reiman Cancer Center	Franklin	Wisconsin
United States	Ascension Southeast Wisconsin Hospital - Franklin	Franklin	Wisconsin
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Smilow Cancer Hospital Care Center at Glastonbury	Glastonbury	Connecticut
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Smilow Cancer Hospital Care Center at Greenwich	Greenwich	Connecticut
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Mount Carmel Grove City Hospital	Grove City	Ohio
United States	Smilow Cancer Hospital Care Center - Guilford	Guilford	Connecticut
United States	UPMC Pinnacle Cancer Center/Community Osteopathic Campus	Harrisburg	Pennsylvania
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	UCHealth Highlands Ranch Hospital	Highlands Ranch	Colorado
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Houston Methodist West Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	Methodist Willowbrook Hospital	Houston	Texas
United States	Ascension Saint Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Lancaster General Ann B Barshinger Cancer Institute	Lancaster	Pennsylvania
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	MD Anderson League City	League City	Texas
United States	Sechler Family Cancer Center	Lebanon	Pennsylvania
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Los Angeles General Medical Center	Los Angeles	California
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Baptist Health Louisville	Louisville	Kentucky
United States	University of Wisconsin Carbone Cancer Center - University Hospital	Madison	Wisconsin
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion	Mechanicsburg	Pennsylvania
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin
United States	Ascension Saint Francis Hospital	Milwaukee	Wisconsin
United States	Ascension Southeast Wisconsin Hospital - Saint Joseph Campus	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	NYU Langone Hospital - Long Island	Mineola	New York
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Virtua Samson Cancer Center	Moorestown	New Jersey
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	Mount Carmel New Albany Surgical Hospital	New Albany	Ohio
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Chelsea	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Mount Sinai West	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	CTCA at Southeastern Regional Medical Center	Newnan	Georgia
United States	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut
United States	Norwalk Hospital	Norwalk	Connecticut
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Nebraska Cancer Specialists/Oncology Hematology West PC - MECC	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Oncology Associates PC	Omaha	Nebraska
United States	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	Paoli Memorial Hospital	Paoli	Pennsylvania
United States	Parker Adventist Hospital	Parker	Colorado
United States	Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Maine Medical Center-Bramhall Campus	Portland	Maine
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Ascension All Saints Hospital	Racine	Wisconsin
United States	Duke Raleigh Hospital	Raleigh	North Carolina
United States	Duke Women's Cancer Care Raleigh	Raleigh	North Carolina
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Carilion Clinic Gynecological Oncology	Roanoke	Virginia
United States	Highland Hospital	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	University of Utah Sugarhouse Health Center	Salt Lake City	Utah
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Houston Methodist Sugar Land Hospital	Sugar Land	Texas
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Houston Methodist The Woodlands Hospital	The Woodlands	Texas
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Virtua Voorhees	Voorhees	New Jersey
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	Ascension Medical Group Southeast Wisconsin - Mayfair Road	Wauwatosa	Wisconsin
United States	Chester County Hospital	West Chester	Pennsylvania
United States	Smilow Cancer Hospital Care Center - Westerly	Westerly	Rhode Island
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Potential transformations of the severity of adverse events	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
Other	Biomarker analysis	Will assess baseline genetic characteristics (e.g. mutations) and microenvironment parameters, treatment, and interactions between treatment and biomarkers in a Cox regression.	Baseline
Other	Functional Assessment of Cancer Therapy (FACT)-Immune Checkpoint Modulator (ICM) subscale	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
Primary	3 year recurrence-free survival	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	Incidence of adverse events	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
Secondary	Recurrence patterns	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
Secondary	5 year recurrence free survival	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
Secondary	Overall survival	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
Secondary	Patient-reported outcomes	Will be assessed by questionnaire.	Up to 2 years after starting treatment
Secondary	Impact of circulating tumor deoxyribonucleic acid (ctDNA) on treatment outcomes	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