Testing Nivolumab With or Without Ipilimumab in Deficient Mismatch Repair System (dMMR) Recurrent Endometrial Carcinoma
Start Date
6/2/2022
Completion Date
7/30/2032
Summary
This phase II trial tests whether the combination of nivolumab and ipilimumab is better than nivolumab alone to shrink tumors in patients with deficient mismatch repair system (dMMR) endometrial carcinoma that has come back after a period of time during which the cancer could not be detected (recurrent). Deoxyribonucleic acid (DNA) mismatch repair (MMR) is a system for recognizing and repairing damaged DNA. In 2-3% of endometrial cancers this may be due to a hereditary condition resulted from gene mutation called Lynch Syndrome (previously called hereditary nonpolyposis colorectal cancer or HNPCC). MMR deficient cells usually have many DNA mutations. Tumors that have evidence of mismatch repair deficiency tend to be more sensitive to immunotherapy. There is some evidence that nivolumab with ipilimumab can shrink or stabilize cancers with deficient mismatch repair system. However, it is not known whether this will happen in endometrial cancer; therefore, this study is designed to answer that question. Monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab in combination with ipilimumab may be better than nivolumab alone in treating dMMR recurrent endometrial carcinoma.
Detailed Description
PRIMARY OBJECTIVE: I. To assess efficacy in terms of progression-free survival (PFS) for immunotherapy with dual immune checkpoint blockade (nivolumab/ipilimumab) versus (vs.) monotherapy (nivolumab) in patients with recurrent mismatch repair (MMR) deficient endometrial carcinoma with measurable or non-measurable (detectable) disease. SECONDARY OBJECTIVES: I. To evaluate the overall survival (OS) as estimated from time of enrollment to last follow-up or death. II. To evaluate the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in those with measurable disease at start of treatment. III. To evaluate progression-free survival at 6 months. IV. To evaluate the nature, frequency and degree of toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. V. To evaluate PFS and objective response rate in patients with prior anti-PD1/PDL1 therapy and compare efficacy of dual immune checkpoint inhibition vs. anti-PD1 monotherapy. OUTLINE: Patients are randomized into 1 of 2 arms. ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle and ipilimumab IV over 90 minutes on day 1 of every other cycle. Cycles repeat every three weeks. Treatment with nivolumab and ipilimumab repeats for up to 8 cycles in the absence of disease progression, unacceptable toxicity, or complete response (CR). Patients then receive nivolumab alone on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression, unacceptable toxicity, or CR. ARM II: Patients receive nivolumab IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for up to 8 cycles, then every 4 weeks thereafter in the absence of disease progression, unacceptable toxicity, or CR. MAINTENANCE THERAPY: Patients achieving CR on Arm I or II receive nivolumab for an additional 12 months in the absence of disease progression or unacceptable toxicity. Additionally, all patients may optionally undergo collection of tissue samples on study as well as blood samples throughout the trial. All patients also undergo computed tomography (CT) scan and/or magnetic resonance imaging (MRI) throughout the trial. Patients are followed every 3 months for 2 years, and then, every 6 months for 3 years.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Biospecimen Collection
Computed Tomography
Ipilimumab
Magnetic Resonance Imaging
Nivolumab
Conditions
Locations
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233
United States
University Cancer and Blood Center LLC
Athens, Georgia 30607
United States
Augusta University Medical Center
Augusta, Georgia 30912
United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho 83706
United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho 83712
United States
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho 83605
United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho 83814
United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho 83619
United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho 83642
United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho 83687
United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho 83687
United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho 83854
United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho 83864
United States
University of Illinois
Chicago, Illinois 60612
United States
Carle at The Riverfront
Danville, Illinois 61832
United States
Carle Physician Group-Effingham
Effingham, Illinois 62401
United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois 61938
United States
Carle BroMenn Medical Center
Normal, Illinois 61761
United States
Carle Cancer Institute Normal
Normal, Illinois 61761
United States
Carle Cancer Center
Urbana, Illinois 61801
United States
IU Health North Hospital
Carmel, Indiana 46032
United States
Northwest Cancer Center - Crown Point
Crown Point, Indiana 46307
United States
Northwest Oncology LLC
Dyer, Indiana 46311
United States
Northwest Cancer Center - Hobart
Hobart, Indiana 46342
United States
Saint Mary Medical Center
Hobart, Indiana 46342
United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana 46202
United States
Saint Catherine Hospital
Indianapolis, Indiana 46312
United States
The Community Hospital
Munster, Indiana 46321
United States
Women's Diagnostic Center - Munster
Munster, Indiana 46321
United States
Northwest Cancer Center - Valparaiso
Valparaiso, Indiana 46383
United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa 52242
United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky 40202
United States
UofL Health Medical Center Northeast
Louisville, Kentucky 40245
United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine 04074
United States
Bronson Battle Creek
Battle Creek, Michigan 49017
United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan 49503
United States
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan 49503
United States
Bronson Methodist Hospital
Kalamazoo, Michigan 49007
United States
West Michigan Cancer Center
Kalamazoo, Michigan 49007
United States
Beacon Kalamazoo Cancer Center
Kalamazoo, Michigan 49009
United States
Trinity Health Muskegon Hospital
Muskegon, Michigan 49444
United States
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan 49120
United States
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan 49444
United States
Corewell Health Reed City Hospital
Reed City, Michigan 49677
United States
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan 49085
United States
Corewell Health Lakeland Hospitals - Saint Joseph Hospital
Saint Joseph, Michigan 49085
United States
Munson Medical Center
Traverse City, Michigan 49684
United States
University of Michigan Health - West
Wyoming, Michigan 49519
United States
Mercy Hospital
Coon Rapids, Minnesota 55433
United States
Essentia Health - Deer River Clinic
Deer River, Minnesota 56636
United States
Essentia Health Cancer Center
Duluth, Minnesota 55805
United States
Miller-Dwan Hospital
Duluth, Minnesota 55805
United States
Fairview Southdale Hospital
Edina, Minnesota 55435
United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota 55746
United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota 55407
United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota 55416
United States
Regions Hospital
Saint Paul, Minnesota 55101
United States
United Hospital
Saint Paul, Minnesota 55102
United States
Essentia Health Sandstone
Sandstone, Minnesota 55072
United States
Saint Francis Regional Medical Center
Shakopee, Minnesota 55379
United States
Essentia Health Virginia Clinic
Virginia, Minnesota 55792
United States
MU Health - University Hospital/Ellis Fischel Cancer Center
Columbia, Missouri 65212
United States
Washington University School of Medicine
St Louis, Missouri 63110
United States
Community Hospital of Anaconda
Anaconda, Montana 59711
United States
Billings Clinic Cancer Center
Billings, Montana 59101
United States
Saint Vincent Frontier Cancer Center
Billings, Montana 59102
United States
Intermountain Health West End Clinic
Billings, Montana 59106
United States
Bozeman Health Deaconess Hospital
Bozeman, Montana 59715
United States
Benefis Sletten Cancer Institute
Great Falls, Montana 59405
United States
Logan Health Medical Center
Kalispell, Montana 59901
United States
Community Medical Center
Missoula, Montana 59804
United States
Nebraska Methodist Hospital
Omaha, Nebraska 68114
United States
Women's Cancer Center of Nevada
Las Vegas, Nevada 89106
United States
University of New Mexico Cancer Center
Albuquerque, New Mexico 87106
United States
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
University of Rochester
Rochester, New York 14642
United States
State University of New York Upstate Medical University
Syracuse, New York 13210
United States
Wilmot Cancer Institute at Webster
Webster, New York 14580
United States
Duke University Medical Center
Durham, North Carolina 27710
United States
Duke Women's Cancer Care Raleigh
Raleigh, North Carolina 27607
United States
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota 58103
United States
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio 44122
United States
Miami Valley Hospital South
Centerville, Ohio 45459
United States
Geauga Hospital
Chardon, Ohio 44024
United States
Good Samaritan Hospital - Cincinnati
Cincinnati, Ohio 45220
United States
Case Western Reserve University
Cleveland, Ohio 44106
United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland, Ohio 44111
United States
Cleveland Clinic Foundation
Cleveland, Ohio 44195
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
Hillcrest Hospital Cancer Center
Mayfield Heights, Ohio 44124
United States
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio 44060
United States
University Hospitals Parma Medical Center
Parma, Ohio 44129
United States
UH Seidman Cancer Center at Saint John Medical Center
Westlake, Ohio 44145
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma 74146
United States
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon 97914
United States
Providence Portland Medical Center
Portland, Oregon 97213
United States
Providence Saint Vincent Medical Center
Portland, Oregon 97225
United States
UPMC-Heritage Valley Health System Beaver
Beaver, Pennsylvania 15009
United States
UPMC Hillman Cancer Center at Butler Health System
Butler, Pennsylvania 16001
United States
UPMC Hillman Cancer Center - Passavant - Cranberry
Cranberry Township, Pennsylvania 16066
United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania 16505
United States
UPMC Cancer Center at UPMC Horizon
Farrell, Pennsylvania 16121
United States
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania 15601
United States
IRMC Cancer Center
Indiana, Pennsylvania 15701
United States
UPMC-Johnstown/John P. Murtha Regional Cancer Center
Johnstown, Pennsylvania 15901
United States
UPMC Cancer Center at UPMC McKeesport
McKeesport, Pennsylvania 15132
United States
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
Mechanicsburg, Pennsylvania 17050
United States
UPMC Hillman Cancer Center - Monroeville
Monroeville, Pennsylvania 15146
United States
UPMC Hillman Cancer Center in Coraopolis
Moon Township, Pennsylvania 15108
United States
UPMC Hillman Cancer Center - Part of Frick Hospital
Mount Pleasant, Pennsylvania 15666
United States
Arnold Palmer Cancer Center Medical Oncology Norwin
N. Huntingdon, Pennsylvania 15642
United States
UPMC Cancer Center-Natrona Heights
Natrona Heights, Pennsylvania 15065
United States
UPMC Hillman Cancer Center - New Castle
New Castle, Pennsylvania 16105
United States
UPMC-Magee Womens Hospital
Pittsburgh, Pennsylvania 15213
United States
UPMC-Saint Margaret
Pittsburgh, Pennsylvania 15215
United States
UPMC-Mercy Hospital
Pittsburgh, Pennsylvania 15219
United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
UPMC-Passavant Hospital
Pittsburgh, Pennsylvania 15237
United States
UPMC-Saint Clair Hospital Cancer Center
Pittsburgh, Pennsylvania 15243
United States
UPMC Cancer Center at UPMC Northwest
Seneca, Pennsylvania 16346
United States
UPMC Cancer Center-Washington
Washington, Pennsylvania 15301
United States
UPMC West Mifflin-Cancer Center Jefferson
West Mifflin, Pennsylvania 15122
United States
Women and Infants Hospital
Providence, Rhode Island 02905
United States
Parkland Memorial Hospital
Dallas, Texas 75235
United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
United States
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth, Texas 76104
United States
UT Southwestern Clinical Center at Richardson/Plano
Richardson, Texas 75080
United States
University of Virginia Cancer Center
Charlottesville, Virginia 22908
United States
Henrico Doctor's Hospital
Richmond, Virginia 23229
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
Swedish Cancer Institute-Edmonds
Edmonds, Washington 98026
United States
Swedish Cancer Institute-Issaquah
Issaquah, Washington 98029
United States
Fred Hutchinson Cancer Center
Seattle, Washington 98109
United States
Swedish Medical Center-First Hill
Seattle, Washington 98122
United States
Duluth Clinic Ashland
Ashland, Wisconsin 54806
United States
Northwest Wisconsin Cancer Center
Ashland, Wisconsin 54806
United States