A Randomized Phase II Trial of Nivolumab and Ipilimumab Compared to Nivolumab Monotherapy in Patients With Deficient Mismatch Repair System Recurrent Endometrial Carcinoma

Who is this study for? Patients with deficient mismatch repair system recurrent endometrial carcinoma
What treatments are being studied? Ipilimumab+Nivolumab
Status: Recruiting
Location: See all (111) locations...
Intervention Type: Procedure, Biological
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: Female
Minimum Age: 18
Healthy Volunteers: f
View:

• Patients with measurable or non-measurable (detectable) recurrent endometrial cancer

• Measurable disease will be defined and monitored by RECIST v 1.1. Measurable disease is defined per RECIST 1.1 criteria 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

• Non-measurable (detectable) disease in a patient is defined in this protocol per RECIST 1.1 criteria as one who does not have measurable disease but has at least one of the following conditions:

‣ All other lesions (or sites of disease), including small lesions (longest diameter \<10 mm or pathological lymph nodes with \>= 10 to \< 15 mm short axis), are considered non-measurable disease

⁃ Ascites and/or pleural effusion attributed to tumor

⁃ Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions

• Patients must have endometrial cancer with deficient mismatch repair system. All patients must have institutional immunohistochemistry (IHC) and/or microsatellite instability (MSI) testing to determine mismatch repair (MMR) status. MMR deficiency is defined as lack of expression of one or more mismatch repair proteins (MLH1, PMS2, MSH2, MSH6, EPCAM) by immunohistochemistry and/or presence of microsatellite instability high using the National Cancer Institute (NCI)-5plex and Promega v1.2 assays, or institutional standards (e.g. next-generation sequencing \[NGS\] panel)

‣ Method(s) of detection of MMR deficiency will be recorded for each patient. An institutional pathology report, and additional reports if available, documenting these results must be submitted. Patients with equivocal results on MMR testing by immunohistochemistry may be eligible if they have documented evidence of microsatellite instability by MSI testing or by next generation sequencing assays. MMR testing by IHC may be used to resolve equivocal/indeterminate MSI results

• 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, mucinous adenocarcinoma, dedifferentiated/undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.)

• Patients may have received 1-2 prior lines of systemic therapy:

‣ Prior anti-PD1/PD-L1 therapy is allowed if given in combination with chemotherapy or radiation therapy in adjuvant or primary metastatic/recurrent settings. Patients must have had a complete response and have disease progression/relapse with treatment-free interval of 12 months or more from last dose of therapy with immune check inhibition

• 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 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 registration

• Any other prior therapy directed at the malignant tumor including chemotherapy, targeted agents, biologic agents, immunologic agents, and any investigational agents, must be discontinued at least 4 weeks prior to registration (6 weeks for nitrosoureas or mitomycin C)

• Age \>= 18

• Eastern Cooperative Oncology Group (ECOG) 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 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

• Adequate oxygen saturation via pulse oximeter (CTCAE v.5.0 hypoxia \< grade 2 within 28 days prior to registration)

• Thyroid-stimulating hormone (TSH) within normal limits (TSH \< ULN allowed in euthyroid patients on thyroid replacement therapy). TSH testing is only required if clinically indicated

• Patients must have recovered from effects of recent surgery, radiotherapy or chemotherapy. At least 4 weeks must have elapsed since major surgery

• As clinically indicated, patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better and have a corrected QT (QTc) interval \< 450 msec

• The effects of nivolumab, and ipilimumab on the developing human fetus are unknown. For this reason and because nivolumab and ipilimumab are known to be teratogenic, women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 5 months after the last dose of investigational drug. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) do not require contraception

‣ WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL

• 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

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

• Patients with evidence of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load 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

• 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 the patient is stable off steroids for at least one month

• 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

• Patients with vitiligo, endocrine deficiencies including 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

Locations
United States
Alabama
University of Alabama at Birmingham Cancer Center
RECRUITING
Birmingham
Georgia
University Cancer and Blood Center LLC
RECRUITING
Athens
Augusta University Medical Center
RECRUITING
Augusta
Iowa
University of Iowa/Holden Comprehensive Cancer Center
RECRUITING
Iowa City
Idaho
Saint Alphonsus Cancer Care Center-Boise
SUSPENDED
Boise
Saint Luke's Cancer Institute - Boise
RECRUITING
Boise
Saint Alphonsus Cancer Care Center-Caldwell
SUSPENDED
Caldwell
Kootenai Health - Coeur d'Alene
RECRUITING
Coeur D'alene
Saint Luke's Cancer Institute - Fruitland
RECRUITING
Fruitland
Saint Luke's Cancer Institute - Meridian
RECRUITING
Meridian
Saint Alphonsus Cancer Care Center-Nampa
SUSPENDED
Nampa
Saint Luke's Cancer Institute - Nampa
RECRUITING
Nampa
Kootenai Clinic Cancer Services - Post Falls
RECRUITING
Post Falls
Kootenai Clinic Cancer Services - Sandpoint
RECRUITING
Sandpoint
Illinois
University of Illinois
RECRUITING
Chicago
Carle at The Riverfront
RECRUITING
Danville
Carle Physician Group-Effingham
RECRUITING
Effingham
Carle Physician Group-Mattoon/Charleston
RECRUITING
Mattoon
Carle Cancer Center
RECRUITING
Urbana
Indiana
IU Health North Hospital
RECRUITING
Carmel
Northwest Cancer Center - Main Campus
RECRUITING
Crown Point
Northwest Oncology LLC
RECRUITING
Dyer
Northwest Cancer Center - Hobart
RECRUITING
Hobart
Saint Mary Medical Center
RECRUITING
Hobart
Indiana University/Melvin and Bren Simon Cancer Center
RECRUITING
Indianapolis
Saint Catherine Hospital
RECRUITING
Indianapolis
The Community Hospital
RECRUITING
Munster
Women's Diagnostic Center - Munster
RECRUITING
Munster
Northwest Cancer Center - Valparaiso
RECRUITING
Valparaiso
Kentucky
The James Graham Brown Cancer Center at University of Louisville
RECRUITING
Louisville
UofL Health Medical Center Northeast
RECRUITING
Louisville
Minnesota
Mercy Hospital
RECRUITING
Coon Rapids
Essentia Health - Deer River Clinic
RECRUITING
Deer River
Essentia Health Cancer Center
RECRUITING
Duluth
Miller-Dwan Hospital
RECRUITING
Duluth
Fairview Southdale Hospital
RECRUITING
Edina
Essentia Health Hibbing Clinic
RECRUITING
Hibbing
Abbott-Northwestern Hospital
RECRUITING
Minneapolis
United Hospital
RECRUITING
Saint Paul
Essentia Health Sandstone
RECRUITING
Sandstone
Essentia Health Virginia Clinic
RECRUITING
Virginia
Missouri
Washington University School of Medicine
RECRUITING
St Louis
Montana
Community Hospital of Anaconda
RECRUITING
Anaconda
Billings Clinic Cancer Center
RECRUITING
Billings
Intermountain Health West End Clinic
RECRUITING
Billings
Saint Vincent Frontier Cancer Center
RECRUITING
Billings
Bozeman Health Deaconess Hospital
RECRUITING
Bozeman
Benefis Sletten Cancer Institute
RECRUITING
Great Falls
Logan Health Medical Center
RECRUITING
Kalispell
Community Medical Center
RECRUITING
Missoula
North Carolina
Duke University Medical Center
RECRUITING
Durham
Duke Women's Cancer Care Raleigh
RECRUITING
Raleigh
North Dakota
Essentia Health Cancer Center-South University Clinic
RECRUITING
Fargo
Nebraska
Nebraska Methodist Hospital
RECRUITING
Omaha
New Mexico
University of New Mexico Cancer Center
RECRUITING
Albuquerque
Nevada
Women's Cancer Center of Nevada
RECRUITING
Las Vegas
New York
Roswell Park Cancer Institute
ACTIVE_NOT_RECRUITING
Buffalo
University of Rochester
RECRUITING
Rochester
State University of New York Upstate Medical University
RECRUITING
Syracuse
Ohio
UHHS-Chagrin Highlands Medical Center
RECRUITING
Beachwood
Geauga Hospital
RECRUITING
Chardon
Good Samaritan Hospital - Cincinnati
RECRUITING
Cincinnati
Case Western Reserve University
RECRUITING
Cleveland
Cleveland Clinic Cancer Center/Fairview Hospital
RECRUITING
Cleveland
Cleveland Clinic Foundation
RECRUITING
Cleveland
Ohio State University Comprehensive Cancer Center
RECRUITING
Columbus
Hillcrest Hospital Cancer Center
RECRUITING
Mayfield Heights
UH Seidman Cancer Center at Lake Health Mentor Campus
RECRUITING
Mentor
UH Seidman Cancer Center at Saint John Medical Center
RECRUITING
Westlake
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Oklahoma Cancer Specialists and Research Institute-Tulsa
RECRUITING
Tulsa
Oregon
Saint Alphonsus Cancer Care Center-Ontario
SUSPENDED
Ontario
Providence Portland Medical Center
RECRUITING
Portland
Providence Saint Vincent Medical Center
RECRUITING
Portland
Pennsylvania
UPMC-Heritage Valley Health System Beaver
RECRUITING
Beaver
UPMC Hillman Cancer Center at Butler Health System
RECRUITING
Butler
UPMC Hillman Cancer Center - Passavant - Cranberry
RECRUITING
Cranberry Township
UPMC Hillman Cancer Center Erie
RECRUITING
Erie
UPMC Cancer Center at UPMC Horizon
RECRUITING
Farrell
UPMC Cancer Centers - Arnold Palmer Pavilion
RECRUITING
Greensburg
IRMC Cancer Center
RECRUITING
Indiana
UPMC-Johnstown/John P. Murtha Regional Cancer Center
RECRUITING
Johnstown
UPMC Cancer Center at UPMC McKeesport
RECRUITING
Mckeesport
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
RECRUITING
Mechanicsburg
UPMC Hillman Cancer Center - Monroeville
RECRUITING
Monroeville
UPMC Hillman Cancer Center in Coraopolis
RECRUITING
Moon Township
UPMC Hillman Cancer Center - Part of Frick Hospital
RECRUITING
Mount Pleasant
Arnold Palmer Cancer Center Medical Oncology Norwin
RECRUITING
N. Huntingdon
UPMC Cancer Center-Natrona Heights
RECRUITING
Natrona Heights
UPMC Hillman Cancer Center - New Castle
RECRUITING
New Castle
University of Pittsburgh Cancer Institute (UPCI)
RECRUITING
Pittsburgh
UPMC-Magee Womens Hospital
RECRUITING
Pittsburgh
UPMC-Mercy Hospital
RECRUITING
Pittsburgh
UPMC-Passavant Hospital
RECRUITING
Pittsburgh
UPMC-Saint Clair Hospital Cancer Center
RECRUITING
Pittsburgh
UPMC-Saint Margaret
RECRUITING
Pittsburgh
UPMC Cancer Center at UPMC Northwest
RECRUITING
Seneca
UPMC Cancer Center-Washington
RECRUITING
Washington
UPMC West Mifflin-Cancer Center Jefferson
RECRUITING
West Mifflin
Rhode Island
Women and Infants Hospital
RECRUITING
Providence
Texas
Parkland Memorial Hospital
RECRUITING
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
RECRUITING
Dallas
UT Southwestern/Simmons Cancer Center-Fort Worth
RECRUITING
Fort Worth
UT Southwestern Clinical Center at Richardson/Plano
RECRUITING
Richardson
Virginia
University of Virginia Cancer Center
RECRUITING
Charlottesville
Henrico Doctor's Hospital
RECRUITING
Richmond
VCU Massey Comprehensive Cancer Center
RECRUITING
Richmond
Washington
Fred Hutchinson Cancer Center
ACTIVE_NOT_RECRUITING
Seattle
Swedish Medical Center-First Hill
RECRUITING
Seattle
Wisconsin
Duluth Clinic Ashland
RECRUITING
Ashland
Northwest Wisconsin Cancer Center
RECRUITING
Ashland
Time Frame
Start Date: 2022-06-02
Estimated Completion Date: 2026-04-30
Participants
Target number of participants: 81
Treatments
Experimental: Arm I (nivolumab and ipilimumab)
Patients receive nivolumab 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 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.~MAINTENANCE THERAPY: Patients achieving CR receive nivolumab for an additional 12 months in the absence of disease progression or unacceptable toxicity.~Additionally, patients may optionally undergo collection of tissue samples on study as well as blood samples throughout the trial. Patients also undergo CT scan and/or MRI throughout the trial.
Active_comparator: Arm II (nivolumab)
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 receive nivolumab for an additional 12 months in the absence of disease progression or unacceptable toxicity.~Additionally, patients may optionally undergo collection of tissue samples on study as well as blood samples throughout the trial. Patients also undergo CT scan and/or MRI throughout the trial.
Sponsors
Leads: National Cancer Institute (NCI)
Collaborators: NRG Oncology

This content was sourced from clinicaltrials.gov

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