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NCT04214067

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

Last Updated: 2025-11-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

168 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-09

Study Completion Date

2025-12-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Endometrial Endometrioid Adenocarcinoma Stage I Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8 Stage II Uterine Corpus Carcinoma or Carcinosarcoma AJCC v8

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood

Brachytherapy

Intervention Type RADIATION

Undergo vaginal brachytherapy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

External Beam Radiation Therapy

Intervention Type RADIATION

Undergo EBRT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

X-Ray Imaging

Intervention Type PROCEDURE

Undergo x-rays

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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood

Brachytherapy

Intervention Type RADIATION

Undergo vaginal brachytherapy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

External Beam Radiation Therapy

Intervention Type RADIATION

Undergo EBRT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

X-Ray Imaging

Intervention Type PROCEDURE

Undergo x-rays

Interventions

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Biospecimen Collection

Undergo collection of blood

Intervention Type PROCEDURE

Brachytherapy

Undergo vaginal brachytherapy

Intervention Type RADIATION

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

External Beam Radiation Therapy

Undergo EBRT

Intervention Type RADIATION

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Pembrolizumab

Given IV

Intervention Type BIOLOGICAL

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

X-Ray Imaging

Undergo x-rays

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Brachytherapy, NOS Internal Radiation Internal Radiation Brachytherapy Internal Radiation Therapy Radiation Brachytherapy Radiation, Internal 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 Definitive Radiation Therapy EBRT External Beam Radiation External Beam Radiotherapy External Beam Radiotherapy (conventional) External Beam RT external radiation External Radiation Therapy external-beam radiation Radiation, External Beam Teleradiotherapy Teletherapy Teletherapy Radiation 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 BCD-201 GME 751 GME751 Keytruda Lambrolizumab MK 3475 MK-3475 MK3475 Pembrolizumab Biosimilar BCD-201 Pembrolizumab Biosimilar GME751 Pembrolizumab Biosimilar QL2107 Pembrolizumab Biosimilar RPH-075 Pembrolizumab Biosimilar SB27 QL2107 RPH 075 RPH-075 RPH075 SB 27 SB-27 SB27 SCH 900475 SCH-900475 SCH900475 Quality of Life Assessment Conventional X-Ray Diagnostic Radiology Medical Imaging, X-Ray Plain film radiographs Radiographic Imaging Radiographic imaging procedure (procedure) Radiography RG Static X-Ray X-Ray

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Floor Backes

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status

Community Cancer Institute

Clovis, California, United States

Site Status

University Oncology Associates

Clovis, California, United States

Site Status

John Muir Medical Center-Concord

Concord, California, United States

Site Status

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status

Los Angeles General Medical Center

Los Angeles, California, United States

Site Status

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Site Status

John Muir Medical Center-Walnut Creek

Walnut Creek, California, United States

Site Status

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, United States

Site Status

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States

Site Status

Memorial Hospital North

Colorado Springs, Colorado, United States

Site Status

AdventHealth Porter

Denver, Colorado, United States

Site Status

UCHealth Highlands Ranch Hospital

Highlands Ranch, Colorado, United States

Site Status

AdventHealth Littleton

Littleton, Colorado, United States

Site Status

AdventHealth Parker

Parker, Colorado, United States

Site Status

Danbury Hospital

Danbury, Connecticut, United States

Site Status

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center at Glastonbury

Glastonbury, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

Site Status

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, United States

Site Status

Norwalk Hospital

Norwalk, Connecticut, United States

Site Status

Smilow Cancer Hospital-Orange Care Center

Orange, Connecticut, United States

Site Status

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States

Site Status

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States

Site Status

GenesisCare USA - FGO

Fort Myers, Florida, United States

Site Status

Regional Cancer Center-Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

Northside Hospital

Atlanta, Georgia, United States

Site Status

Northside Hospital-Forsyth

Cumming, Georgia, United States

Site Status

Wellstar Kennestone Hospital

Marietta, Georgia, United States

Site Status

CTCA at Southeastern Regional Medical Center

Newnan, Georgia, United States

Site Status

Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status