Testing the Addition of the Immunotherapy Drug Pembrolizumab to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) in Stage III-IV or Recurrent Endometrial Cancer

Endometrial Serous Adenocarcinoma Clinical Trial

Official title:

A Phase III Randomized, Placebo-Controlled Study of Pembrolizumab (MK-3475, NSC #776864) in Addition to Paclitaxel and Carboplatin for Measurable Stage III or IVA, Stage IVB or Recurrent Endometrial Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03914612
• Other study ID #: NCI-2019-02186
• Secondary ID: NCI-2019-02186NR
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 16, 2019
• Est. completion date: May 10, 2024

Study information

• Verified date: May 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial studies how well the combination of pembrolizumab, paclitaxel and carboplatin works compared with paclitaxel and carboplatin alone in treating patients with endometrial cancer that is stage III or IV, or has come back after a period of improvement (recurrent). 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. Paclitaxel and carboplatin are chemotherapy drugs used as part of the usual treatment approach for this type of cancer. This study aims to assess if adding immunotherapy to these drugs is better or worse than the usual approach for treatment of this cancer.

Description:

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of pembrolizumab (MK-3475) in combination with paclitaxel and carboplatin in patients with advanced stage (measurable stage III or IVA), stage IVB and recurrent endometrial cancer.

SECONDARY OBJECTIVES:

I. To determine the nature, frequency and degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) for each treatment arm.

II. To evaluate blinded independent central review (BICR) assessed or investigator assessed objective response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by treatment arm and by mismatch repair (MMR) immunohistochemistry (IHC) status in patients who enter the study with measurable disease.

III. To evaluate BICR assessed or investigator assessed duration of response (DOR) by treatment arm and by MMR IHC status in patients who enter the study with measurable disease.

IV. To evaluate the effect of pembrolizumab (MK-3475) on overall survival (OS) in patients with mismatch repair protein proficient (pMMR) or mismatch repair deficiency (dMMR).

V. To determine whether the addition of pembrolizumab (MK-3475) to standard combination chemotherapy is associated with improved patient reported physical function as measured with the Patient-Reported Outcomes Measurement Information System (PROMIS)-physical function scale (short form), quality of life as measured with the Functional Assessment of Cancer Therapy (FACT) - Endometrial Trial Outcome Index (En TOI) and worsened fatigue as measured with the PROMIS-Fatigue scale (short form) in the pMMR patients.

VI. To determine concordance between institutional MMR immunohistochemistry (IHC) testing and centralized MMR IHC.

EXPLORATORY OBJECTIVES:

I. To explore the correlation between patient-reported physical function as measured with the PROMIS-physical function scale (short form) and quality of life as measure with the FACT-En TOI.

II. To explore whether the addition of pembrolizumab (MK-3475) to standard combination chemotherapy is associated with self-reported neurotoxicity as measured with the FACT/Gynecologic Oncology Group Neurotoxicity (GOG-Ntx) subscale (short) and the extent to which patients differ on their self-reported bother from side effects of cancer therapy in the pMMR patients.

III. To evaluate the efficacy of pembrolizumab (MK-3475) in combination with paclitaxel and carboplatin in patients with advanced stage (measurable stage III or IVA), stage IVB and recurrent endometrial cancer by Programmed Death Ligand 1 (PD-L1) IHC (positive versus [vs] negative).

IV. To assess the association between PD-L1 IHC (positive vs negative) and mismatch repair status (pMMR and dMMR).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I:

COMBINATION PHASE: Patients receive placebo intravenously (IV) over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD) or partial response (PR) who still have measurable disease may continue treatment for up to a total 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.

On February 6, 2023, all patient treatment assignments were unblinded. Patients randomized to Arm I will not receive additional placebo infusions.

ARM II:

COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity.

Patients undergo computed tomography (CT) scan throughout the study.

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: 759
• Est. completion date: May 10, 2024
• Est. primary completion date: December 16, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial cancer.

• Pathology report showing results of institutional MMR IHC testing.

• Histologic confirmation of the original primary tumor is required (submission of pathology report(s) is required). Patients with the following histologic types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, dedifferentiated/undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.).

• Submission of tumor specimens for centralized MMR IHC testing is required after Step 1 and before Step 2 registration.

• In patients with measurable disease, lesions will be defined and monitored by RECIST version (v) 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be >= 10 mm when measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI.

• Patients may have received

• NO prior chemotherapy for treatment of endometrial cancer OR

• Prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy [with or without cisplatin]) provided adjuvant chemotherapy was completed >= 12 months prior to STEP 2 registration.

• Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to STEP 2 registration.

• Patients may have received prior hormonal therapy for treatment of endometrial cancer. All hormonal therapy must be discontinued at least three weeks prior to STEP 2 registration.

• Interval or cytoreductive surgery, after start of treatment on this trial, and prior to documentation of disease progression, is NOT permitted.

• Age >= 18

• Performance status of 0, 1 or 2.

• Platelets >= 100,000/mcl.

• Absolute neutrophil count (ANC) >= 1,500/mcl.

• Creatinine =< 1.5 x institutional/laboratory upper limit of normal (ULN).

• Total serum bilirubin level =< 1.5 x upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level =< 3 x ULN may be enrolled).

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN.

• Thyroid stimulating hormone (TSH) within normal limits. If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal Free T4 level is required.

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of Step 2 registration are eligible for this trial.

• For patients of child bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.

• Administration of study drugs (pembrolizumab [MK-3475], paclitaxel, carboplatin) may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality. Women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from at least 14 days prior to Step 2 registration (for oral contraceptives), during treatment, and for 120 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. Patients will be considered of nonreproductive potential if they are either:

• Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age, a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient); OR

• Have a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to Step 2 registration; OR

• Have a congenital or acquired condition that prevents childbearing.

• 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 with 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 pembrolizumab (MK-3475) and/or its excipients; and/or a severe hypersensitivity reaction to paclitaxel and/or carboplatin

• Patients who are currently participating and receiving cancer-directed study therapy or have participated in a study of an investigational agent and received cancer-directed study therapy within 4 weeks prior to Step 2 registration.

• 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 Step 2 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.

• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression, and they have been off steroids for at least 4 weeks prior to Step 2 registration and remain clinically stable.

• 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 who have a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis.

• 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.

• 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.

• Pregnant or lactating patients.

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Carcinoma, Endometrioid
• Endometrial Clear Cell Adenocarcinoma
• Endometrial Dedifferentiated Carcinoma
• Endometrial Endometrioid Adenocarcinoma
• Endometrial Mixed Cell Adenocarcinoma
• Endometrial Neoplasms
• Endometrial Serous Adenocarcinoma
• Endometrial Undifferentiated Carcinoma
• Recurrence
• Recurrent Endometrial Adenocarcinoma
• Recurrent Endometrial Carcinoma
• Recurrent Endometrial Clear Cell Adenocarcinoma
• Recurrent Endometrial Dedifferentiated Carcinoma
• Recurrent Endometrial Endometrioid Adenocarcinoma
• Recurrent Endometrial Mixed Cell Adenocarcinoma
• Recurrent Endometrial Serous Adenocarcinoma
• Recurrent Endometrial Undifferentiated Carcinoma
• Stage III Uterine Corpus Cancer AJCC v8
• Stage IV Uterine Corpus Cancer AJCC v8

Intervention

Drug:
• Carboplatin
Given IV

Procedure:
• Computed Tomography
Undergo CT scan

Drug:
• Paclitaxel
Given IV

Biological:
• Pembrolizumab
Given IV

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

Locations

Country	Name	City	State
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Hopital de la Cite-de-la-Sante	Laval	Quebec
Canada	London Regional Cancer Program	London	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Lakeridge Health Oshawa	Oshawa	Ontario
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Algoma District Cancer Program Sault Area Hospital	Sault Ste Marie	Ontario
Canada	Health Sciences North	Sudbury	Ontario
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Japan	Kure National Hospital	Kure	Hiroshima
Japan	Niigata University Medical and Dental Hospital	Niigata City	Niigata
Japan	Saitama Medical University International Medical Center	Saitama
Japan	Ehime University Hospital	Toon	Ehime
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Keimyung University-Dongsan Medical Center	Dalseo-gu	Daegu
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam City	Kyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea Cancer Center Hospital	Seoul
Korea, Republic of	Samsung Changwon Hospital	Seoul	Gyeongsangnam-do
Korea, Republic of	Yonsei University Health System-Severance Hospital	Seoul
Puerto Rico	Centro Comprensivo de Cancer de UPR	San Juan
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Grady Health System	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	WellStar Cobb Hospital	Austell	Georgia
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	MedStar Franklin Square Medical Center/Weinberg Cancer Institute	Baltimore	Maryland
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Our Lady of The Lake	Baton Rouge	Louisiana
United States	Our Lady of the Lake Medical Oncology	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physicians Group - Medical Oncology	Baton Rouge	Louisiana
United States	Woman's Hospital	Baton Rouge	Louisiana
United States	Northwell Health Imbert Cancer Center	Bay Shore	New York
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	UM Upper Chesapeake Medical Center	Bel Air	Maryland
United States	Waldo County General Hospital	Belfast	Maine
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Sanford Joe Lueken Cancer Center	Bemidji	Minnesota
United States	Saint Charles Health System	Bend	Oregon
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
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 Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Florida Cancer Specialists - Bradenton Cancer Center	Bradenton	Florida
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Island Gynecologic Oncology	Brightwaters	New York
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	New York-Presbyterian/Brooklyn Methodist Hospital	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Aultman Health Foundation	Canton	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Geauga Hospital	Chardon	Ohio
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	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	University of Illinois	Chicago	Illinois
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
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	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Community Cancer Institute	Clovis	California
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
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	Atrium Health Cabarrus/LCI-Concord	Concord	North Carolina
United States	Northwest Cancer Center - Main Campus	Crown Point	Indiana
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	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Northwest Oncology LLC	Dyer	Indiana
United States	University of Maryland Shore Medical Center at Easton	Easton	Maryland
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Saint Elizabeth Healthcare Edgewood	Edgewood	Kentucky
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	University of Kansas Clinical Research Center	Fairway	Kansas
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Piedmont Fayette Hospital	Fayetteville	Georgia
United States	Genesee Cancer and Blood Disease Treatment Center	Flint	Michigan
United States	Genesee Hematology Oncology PC	Flint	Michigan
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	The New York Hospital Medical Center of Queens	Flushing	New York
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Northeast Georgia Medical Center-Gainesville	Gainesville	Georgia
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	CTCA at Western Regional Medical Center	Goodyear	Arizona
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	North Colorado Medical Center	Greeley	Colorado
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
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 - Guilford	Guilford	Connecticut
United States	Cherry Tree Cancer Center	Hanover	Pennsylvania
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Hartford Hospital	Hartford	Connecticut
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Northwest Cancer Center - Hobart	Hobart	Indiana
United States	Saint Mary Medical Center	Hobart	Indiana
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Medical 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	Methodist Willowbrook Hospital	Houston	Texas
United States	Ascension Saint Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	Community Cancer Center East	Indianapolis	Indiana
United States	Community Cancer Center North	Indianapolis	Indiana
United States	Community Cancer Center South	Indianapolis	Indiana
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Saint Catherine Hospital	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Kaiser Permanente-Irvine	Irvine	California
United States	Mississippi Baptist Medical Center	Jackson	Mississippi
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	Jefferson Hospital	Jefferson Hills	Pennsylvania
United States	UPMC-Johnstown/John P. Murtha Regional Cancer Center	Johnstown	Pennsylvania
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Monmouth Medical Center Southern Campus	Lakewood	New Jersey
United States	City of Hope Antelope Valley	Lancaster	California
United States	Lancaster General Ann B Barshinger Cancer Institute	Lancaster	Pennsylvania
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Sparrow Hospital	Lansing	Michigan
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Sechler Family Cancer Center	Lebanon	Pennsylvania
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Los Angeles County-USC 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	McKee Medical Center	Loveland	Colorado
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Lowell General Hospital	Lowell	Massachusetts
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	WellStar Health System Inc	Marietta	Georgia
United States	Wellstar Kennestone Hospital	Marietta	Georgia
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
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	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	NYU Winthrop Hospital	Mineola	New York
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Forbes Hospital	Monroeville	Pennsylvania
United States	UPMC Hillman Cancer Center - Monroeville	Monroeville	Pennsylvania
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	Monongalia Hospital	Morgantown	West Virginia
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	The Community Hospital	Munster	Indiana
United States	Women's Diagnostic Center - Munster	Munster	Indiana
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
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	Ochsner Baptist Medical Center	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	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	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Helen F Graham Cancer Center	Newark	Delaware
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	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Saint Joseph Hospital - Orange	Orange	California
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	University of Chicago Medicine-Orland Park	Orland Park	Illinois
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	University of Kansas Hospital-Indian Creek Campus	Overland Park	Kansas
United States	The Valley Hospital-Luckow Pavilion	Paramus	New Jersey
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	West Penn Hospital	Pittsburgh	Pennsylvania
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Geisinger Cancer Services-Pottsville	Pottsville	Pennsylvania
United States	Women and Infants Hospital	Providence	Rhode Island
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mercy Oncology Center	Redding	California
United States	Mercy Regional Cancer Center	Redding	California
United States	Valley Medical Center	Renton	Washington
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Neurosurgeons of New Jersey-Ridgewood	Ridgewood	New Jersey
United States	Valley Hospital	Ridgewood	New Jersey
United States	Kaiser Permanente-Riverside	Riverside	California
United States	Highland Hospital	Rochester	New York
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Kaiser Permanente-Roseville	Roseville	California
United States	WellStar North Fulton Hospital	Roswell	Georgia
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Mercy Cancer Center - Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	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	Kaiser Permanente-San Diego Zion	San Diego	California
United States	Naval Medical Center -San Diego	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Zuckerberg San Francisco General Hospital	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Florida Cancer Specialists - Sarasota	Sarasota	Florida
United States	Florida Cancer Specialists - Sarasota Downtown	Sarasota	Florida
United States	Sarasota Memorial Hospital	Sarasota	Florida
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	Community Medical Center	Scranton	Pennsylvania
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic	Sioux Falls	South Dakota
United States	WellStar Vinings Health Park	Smyrna	Georgia
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	City of Hope South Pasadena	South Pasadena	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Clinic	Springfield	Illinois
United States	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut
United States	Staten Island University Hospital	Staten Island	New York
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	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Houston Methodist The Woodlands Hospital	The Woodlands	Texas
United States	Community Medical Center	Toms River	New Jersey
United States	Smilow Cancer Hospital-Torrington Care Center	Torrington	Connecticut
United States	Munson Medical Center	Traverse City	Michigan
United States	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	City of Hope Upland	Upland	California
United States	Carle Cancer Center	Urbana	Illinois
United States	Westchester Medical Center	Valhalla	New York
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Northwest Cancer Center - Valparaiso	Valparaiso	Indiana
United States	Legacy Salmon Creek Hospital	Vancouver	Washington
United States	Florida Cancer Specialists - Venice Healthpark	Venice	Florida
United States	Florida Cancer Specialists - Venice Island	Venice	Florida
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	John Muir Medical Center-Walnut Creek	Walnut Creek	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut
United States	Smilow Cancer Hospital Care Center - Waterford	Waterford	Connecticut
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Valley Medical Group - Wayne Multispecialty Practice	Wayne	New Jersey
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Reading Hospital	West Reading	Pennsylvania
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Valley Health System-Hematology/Oncology	Westwood	New Jersey
United States	Wexford Health and Wellness Pavilion	Wexford	Pennsylvania
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Asplundh Cancer Pavilion	Willow Grove	Pennsylvania
United States	Novant Health New Hanover Regional Medical Center	Wilmington	North Carolina
United States	Winchester Hospital	Winchester	Massachusetts
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center - Memorial Division	Worcester	Massachusetts
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (3)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Canadian Cancer Trials Group, NRG Oncology

Countries where clinical trial is conducted

United States,  Canada,  Japan,  Korea, Republic of,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	Will be tested with a stratified log-rank statistic.	Duration of time from study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 5 years
Secondary	Incidence of adverse events	Assessed by Common Terminology Criteria for Adverse Events (CTCAE). Toxicities will be screened for differences between treatments by using an exact method or a Chi-Square test. For a given adverse event, each patient will be graded according to the worse grade experienced while on therapy (and within 30 days of treatment). These toxicities will then be divided into two or three categories such as mild, moderate, and severe or mild to moderate versus severe. The rates of severe toxicities may be characterized by risk ratios or odds ratios with confidence intervals (unadjusted for multiplicity). The number of toxicities examined is usually fairly large, so these analyses will be considered exploratory and may be inspected in light of other studies.	5 years
Secondary	Objective tumor response	Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1.	5 years
Secondary	Duration of objective response	The time difference between the dates of first response and first progression; patients who do not progress are considered censored.	5 years
Secondary	Overall survival (OS)		Time from study entry to time of death or the date of last contact, assessed up to 5 years
Secondary	Quality of life (QoL) and patient-reported outcomes (PROs)	Measured by the Function Assessment of Cancer Therapy (FACT)-Endometrial Trial Outcome Index (En-TOI), the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity (Ntx) subscale (short), Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue (short form),the PROMIS-physical function (short form) and a single-item measuring bother from side effects of cancer therapy. A linear mixed model for repeated measures will be used to estimate and compare the mean differences between the treatment groups. Model covariates will include the patients' randomly assigned study treatment, age at enrollment onto the study, pre-treatment quality of life/patient reported outcome score, assessment time and treatment-by-time interaction. The stratification factors will be the same factors included in the clinical primary analysis. Hochberg's step-up multiple testing procedure (Hochberg, 1988) will be used to adjust p-values for each assessment time points estimated from the fitted model.	5 years
Secondary	Incidence of pembrolizumab treatment and self-reported neurotoxicity	Assessed with FACT/GOG-Ntx.	5 years
Secondary	Concordance between Institutional Mismatch repair (MMR) immunohistochemistry (IHC) testing and centralized MMR IHC	Concordance between institutional MMR IHC testing and centralized MMR IHC. The patient's MMR IHC status will be assessed for prognostic value by conducting stratified log-rank tests or Cox Proportional Hazards (PH) modeling when assessing the impact on PFS or OS. When assessing the impact on the probability of response, a logistic regression model will be considered and include other pertinent variables that may influence response. A Cox PH model will be used to assess predictive value of MMR IHC status for regimen efficacy through an interaction term. A similar type of analysis may be attempted with response using logistic regression. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics such as kappa statistics (e.g. Cohen's kappa coefficient).	5 years
Secondary	Effect of pembrolizumab on PFS and OS by Program Death Ligand 1 (PD-L1) IHC	Will assess the effect of pembrolizumab on PFS and OS by PD-L1 (combined positive score [CPS]) within proficient MMR (pMMR) and deficient MMR (dMMR) populations. The effectiveness of pembrolizumab will be compared by PD-L1 status (CPS). A formal test will be conducted by examining the interaction term between pembrolizumab treatment (yes or no) with PD-L1 status. The association between PD-L1 CPS status and MMR IHC status will be assessed with odds ratios. A test may be conducted with a Fisher's Exact Test, and confidence intervals will be provided.	5 years
Secondary	Association between PD-L1 IHC and MMR status	Measures of association between PD-L1 IHC (CPS) and MMR IHC status. The concordance of institutional MMR IHC testing and centralized MMR IHC will be characterized by agreement statistics such as kappa statistics (e.g. Cohen's kappa coefficient).	5 years