Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer

A Phase II Evaluation of Nivolumab, a Fully Human Antibody Against PD-1, in the Treatment of Persistent or Recurrent Cervical Cancer

This phase II trial studies the side effects and how well nivolumab works in treating patients with cervical cancer that has grown, come back, or spread to other places in the body. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Recurrent Cervical Carcinoma; Stage IV Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Nivolumab

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the antitumor activity (proportion of objective response by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) of nivolumab with objective tumor response in patients with persistent, recurrent or metastatic carcinoma of the cervix.

II. To determine the nature and degree of toxicity of nivolumab as assessed by Common Terminology Criteria for Adverse Events (CTCAE) in patients with persistent, recurrent or metastatic carcinoma of the cervix.

SECONDARY OBJECTIVES:

I. To estimate the duration of progression-free survival (PFS) and overall survival (OS).

TERTIARY OBJECTIVES:

I. To systematically evaluate programmed cell death (PD)-1 and B7 homolog 1 (B7-H1) (i.e., PD-1 ligand) expression in tumor infiltrating lymphocytes (TILs) and cervical cancer cells and explore their correlations with objective response, PFS, and OS in nivolumab-treated patients with PD-1 and B7-H1 scoring results.

II. To explore the composition of immune infiltrates in tumor specimens/biopsies from primary and/or metastatic/recurrent sites with selected markers including (but not limited) to cluster of differentiation (CD)4+, CD8+, forkhead box P3 (FoxP3), CD25, lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin mucin-3 (TIM-3), and inducible T-cell co-stimulator (ICOS) and their correlations to objective response, PFS and OS in nivolumab-treated patients.

III. To evaluate human papillomavirus (HPV) status and to explore the changes of pre- and post-immune therapy responses to HPV16/18/31/35/45 E7 antigens in patients peripheral blood lymphocytes (PBL) and serum using proliferative and interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) (cellular immunity) and serological (enzyme-linked immunosorbent assay [ELISA]) assays.

IV. To explore the levels of circulating tumor cells (CTCs) pre-treatment and at 8 and 12 weeks and their association with patient outcome.

OUTLINE:

Patients receive nivolumab intravenously (IV) over approximately 60 minutes every 2 weeks for a maximum of 46 doses over 92 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Alaska
    • Anchorage, Alaska, United States, 98508
      • Anchorage Associates in Radiation Medicine
    • Anchorage, Alaska, United States, 99508
      • Alaska Breast Care and Surgery LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
    • Anchorage, Alaska, United States, 99508
      • Anchorage Oncology Centre
    • Anchorage, Alaska, United States, 99508
      • Katmai Oncology Group
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
    • Anchorage, Alaska, United States, 99504
      • Anchorage Radiation Therapy Center
    • Anchorage, Alaska, United States, 99508
      • Alaska Regional Hospital
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • CHI Saint Vincent Cancer Center Hot Springs
  • California
    • Auburn, California, United States, 95602
      • Sutter Auburn Faith Hospital
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Baldwin Park, California, United States, 91706
      • Kaiser Permanente-Baldwin Park
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Burlingame, California, United States, 94010
      • Mills-Peninsula Medical Center
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • Davis, California, United States, 95616
      • Sutter Davis Hospital
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Camino Division
    • Mountain View, California, United States, 94040
      • Palo Alto Medical Foundation-Gynecologic Oncology
    • Palo Alto, California, United States, 94301
      • Palo Alto Medical Foundation Health Care
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Roseville, California, United States, 95661
      • Sutter Roseville Medical Center
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • San Diego, California, United States, 92120
      • Kaiser Permanente-San Diego Zion
    • San Diego, California, United States, 92108
      • Kaiser Permanente-San Diego Mission
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center-Pacific Campus
    • San Marcos, California, United States, 92078
      • Kaiser Permanente-San Marcos
    • Santa Cruz, California, United States, 95065
      • Palo Alto Medical Foundation-Santa Cruz
    • Santa Rosa, California, United States, 95403
      • Sutter Pacific Medical Foundation
    • Sunnyvale, California, United States, 94086
      • Palo Alto Medical Foundation-Sunnyvale
    • Vacaville, California, United States, 95687
      • Sutter Cancer Centers Radiation Oncology Services-Vacaville
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Delaware Clinical and Laboratory Physicians PA
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Newark, Delaware, United States, 19713
      • Christiana Gynecologic Oncology LLC
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
    • Seaford, Delaware, United States, 19973
      • TidalHealth Nanticoke / Allen Cancer Center
    • Wilmington, Delaware, United States, 19801
      • Christiana Care Health System-Wilmington Hospital
  • Georgia
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
    • Savannah, Georgia, United States, 31404
      • Summit Cancer Care-Memorial
    • Savannah, Georgia, United States, 31404
      • Low Country Cancer Care
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Health - Coeur d'Alene
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Luke's Cancer Institute - Nampa
    • Post Falls, Idaho, United States, 83854
      • Kootenai Clinic Cancer Services - Post Falls
    • Sandpoint, Idaho, United States, 83864
      • Kootenai Cancer Clinic
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Cancer Institute - Twin Falls
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carbondale, Illinois, United States, 62902
      • Memorial Hospital of Carbondale
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Hinsdale, Illinois, United States, 60521
      • Sudarshan K Sharma MD Limited-Gynecologic Oncology
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • O'Fallon, Illinois, United States, 62269
      • Cancer Care Center of O'Fallon
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Radiation Oncology of Northern Illinois
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Springfield, Illinois, United States, 62702
      • Central Illinois Hematology Oncology Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Sidney and Lois Eskenazi Hospital
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Iowa
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Council Bluffs, Iowa, United States, 51503
      • Alegent Health Mercy Hospital
    • Creston, Iowa, United States, 50801
      • Greater Regional Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50314
      • Mission Cancer and Blood - Laurel
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67905
      • Cancer Center of Kansas-Liberal
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Flaget Memorial Hospital
    • Corbin, Kentucky, United States, 40701
      • Commonwealth Cancer Center-Corbin
    • Lexington, Kentucky, United States, 40504
      • Saint Joseph Radiation Oncology Resource Center
    • Lexington, Kentucky, United States, 40509
      • Saint Joseph Hospital East
    • Louisville, Kentucky, United States, 40202
      • Jewish Hospital
    • Louisville, Kentucky, United States, 40245
      • UofL Health Medical Center Northeast
    • Louisville, Kentucky, United States, 40215
      • Saints Mary and Elizabeth Hospital
    • Shepherdsville, Kentucky, United States, 40165
      • Jewish Hospital Medical Center South
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center- Scarborough Campus
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Dearborn, Michigan, United States, 48126
      • Henry Ford Medical Center-Fairlane
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • Weisberg Cancer Treatment Center
    • Novi, Michigan, United States, 48377
      • Henry Ford Medical Center-Columbus
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Bonne Terre, Missouri, United States, 63628
      • Parkland Health Center-Bonne Terre
    • Branson, Missouri, United States, 65616
      • Cox Cancer Center Branson
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Southwest Campus
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital Joplin
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic-Rolla-Cancer and Hematology
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • BJC Outpatient Center at Sunset Hills
  • Montana
    • Anaconda, Montana, United States, 59711
      • Community Hospital of Anaconda
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
    • Kearney, Nebraska, United States, 68845
      • Heartland Hematology and Oncology
    • Lincoln, Nebraska, United States, 68510
      • Saint Elizabeth Regional Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68130
      • Alegent Health Lakeside Hospital
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68122
      • Hematology and Oncology Consultants PC
    • Papillion, Nebraska, United States, 68046
      • Midlands Community Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Women's Cancer Center of Nevada
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Voorhees, New Jersey, United States, 08043
      • MD Anderson Cancer Center at Cooper-Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87106
      • Southwest Gynecologic Oncology Associates Inc
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Clinton, North Carolina, United States, 28328
      • Sampson Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
    • Jacksonville, North Carolina, United States, 28546
      • Onslow Memorial Hospital
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Belpre, Ohio, United States, 45714
      • Strecker Cancer Center-Belpre
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South
    • Centerville, Ohio, United States, 45459
      • Dayton Physicians LLC-Miami Valley South
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital - Cincinnati
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care Inc-Kenwood
    • Cincinnati, Ohio, United States, 45247
      • TriHealth Cancer Institute-Westside
    • Cincinnati, Ohio, United States, 45255
      • TriHealth Cancer Institute-Anderson
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Columbus, Ohio, United States, 43214
      • Columbus Oncology and Hematology Associates Inc
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43213
      • Mount Carmel East Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Dayton Physician LLC-Miami Valley Hospital North
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Delaware, Ohio, United States, 43015
      • Delaware Health Center-Grady Cancer Center
    • Delaware, Ohio, United States, 43015
      • Delaware Radiation Oncology
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Findlay, Ohio, United States, 45840
      • Armes Family Cancer Center
    • Findlay, Ohio, United States, 45840
      • Orion Cancer Care
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Franklin, Ohio, United States, 45005
      • Dayton Physicians LLC-Atrium
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Greenville, Ohio, United States, 45331
      • Dayton Physicians LLC-Wayne
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Kettering, Ohio, United States, 45409
      • Greater Dayton Cancer Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Marietta, Ohio, United States, 45750
      • Marietta Memorial Hospital
    • Marion, Ohio, United States, 43302
      • OhioHealth Marion General Hospital
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mayfield Heights, Ohio, United States, 44124
      • UH Seidman Cancer Center at Landerbrook Health Center
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Middletown, Ohio, United States, 45042
      • Dayton Physicians LLC-Signal Point
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Newark Radiation Oncology
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Sidney, Ohio, United States, 45365
      • Dayton Physicians LLC-Wilson
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Cancer Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Troy, Ohio, United States, 45373
      • Dayton Physicians LLC - Troy
    • Wadsworth, Ohio, United States, 44281
      • University Hospitals Sharon Health Center
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Oregon
    • Bend, Oregon, United States, 97701
      • Saint Charles Health System
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Clackamas, Oregon, United States, 97015
      • Providence Cancer Institute Clackamas Clinic
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Jefferson Abington Hospital
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Chadds Ford, Pennsylvania, United States, 19317
      • Christiana Care Health System-Concord Health Center
    • Ephrata, Pennsylvania, United States, 17522
      • Ephrata Cancer Center
    • Gettysburg, Pennsylvania, United States, 17325
      • Adams Cancer Center
    • Hanover, Pennsylvania, United States, 17331
      • Cherry Tree Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • York, Pennsylvania, United States, 17403
      • WellSpan Health-York Cancer Center
    • York, Pennsylvania, United States, 17403
      • WellSpan Health-York Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Easley, South Carolina, United States, 29640
      • Prisma Health Cancer Institute - Easley
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Butternut
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
    • Greenville, South Carolina, United States, 29601
      • Greenville Health System Cancer Institute-Andrews
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Memorial Hospital
    • Hixson, Tennessee, United States, 37343
      • Pulmonary Medicine Center of Chattanooga-Hixson
    • Ooltewah, Tennessee, United States, 37363
      • Memorial GYN Plus
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • South Jordan, Utah, United States, 84009
      • South Jordan Health Center
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
  • Washington
    • Aberdeen, Washington, United States, 98520
      • Providence Regional Cancer System-Aberdeen
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Bellevue, Washington, United States, 98005
      • Swedish Cancer Institute-Eastside Oncology Hematology
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Bremerton, Washington, United States, 98310
      • Harrison Medical Center
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Edmonds, Washington, United States, 98026
      • Swedish Cancer Institute-Edmonds
    • Enumclaw, Washington, United States, 98022
      • Saint Elizabeth Hospital
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Lacey, Washington, United States, 98503
      • Providence Regional Cancer System-Lacey
    • Lakewood, Washington, United States, 98499
      • Saint Clare Hospital
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center - Montlake
    • Seattle, Washington, United States, 98109
      • FHCC South Lake Union
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98133
      • University of Washington Medical Center - Northwest
    • Seattle, Washington, United States, 98133
      • Women's Cancer Center of Seattle
    • Shelton, Washington, United States, 98584
      • Providence Regional Cancer System-Shelton
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology PS
    • Spokane, Washington, United States, 99204
      • MultiCare Deaconess Cancer and Blood Specialty Center - Downtown
    • Spokane Valley, Washington, United States, 99216
      • MultiCare Deaconess Cancer and Blood Specialty Center - Valley
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties PLLC
    • Tacoma, Washington, United States, 98405
      • Franciscan Research Center-Northwest Medical Plaza
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
    • Yelm, Washington, United States, 98597
      • Providence Regional Cancer System-Yelm
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Monongalia Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College Of Wisconsin
  • Wyoming
    • Cody, Wyoming, United States, 82414
      • Big Horn Basin Cancer Center
    • Cody, Wyoming, United States, 82414
      • Billings Clinic-Cody
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have persistent, recurrent or metastatic squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix with documented disease progression (disease not amendable to curative therapy); NOTE: the following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma and mesonephric carcinoma; histologic confirmation of the original primary tumor is required via the pathology report
• All patents must have measurable disease as defined by RECIST 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), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI
• Patients must have at least one "target" lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

• Appropriate for study entry based on the following diagnostic workup:

  • History/physical examination within 28 days prior to registration
  • Imaging of target lesion(s) within 28 days prior to registration

  • Further protocol-specific assessments:

    • Recovery from adverse effects of recent surgery, radiotherapy or chemotherapy
    • Any other prior therapy directed at the malignant tumor including chemotherapy, biologic/targeted agents and immunologic agents must be discontinued at least three weeks prior to registration
    • Investigation agents must be discontinued for at least 30 days prior to registration
    • Any prior radiation therapy must be completed at least 4 weeks prior to registration
    • At least 4 weeks must have elapsed since any major surgery prior to registration
• Patients must have had one prior systemic chemotherapeutic regimen for management of persistent, recurrent or metastatic carcinoma of the cervix (e.g.; paclitaxel/cisplatin, paclitaxel/cisplatin/bevacizumab); chemotherapy administered concurrent with primary radiation (e.g.; weekly cisplatin) is not counted as a systemic chemotherapy regimen; adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen (e.g.; paclitaxel and carboplatin for up to 4 cycles); NOTE: patients who have received more than one prior regimen are NOT eligible
• Performance status of 0 or 1
• Absolute neutrophil count (ANC) >= 1,500/ul
• Platelets >= 100,000/ul
• Creatinine =< 1.5 x institutional upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min using Cockcroft-Gault formula
• Bilirubin =< 1.5 x ULN
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
• Normal thyroid function testing (thyroid stimulating hormone [TSH]) within 14 days prior to registration
• The patient or a legally authorized representative must provide study-specific informed consent authorization permitting release of personal health information prior to study entry

Exclusion Criteria:

• Patients who have had prior therapy with nivolumab or with an anti-PD-1, anti-PD-ligand (L)1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways
• History of severe hypersensitivity reaction to any monoclonal antibody
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients who are pregnant or nursing; 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 the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IV/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 or have undergone definitive radiation) do not require contraception
  • Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy of bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 month 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 greater than 40 mIU/mL
  • WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product
  • Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform the treating physician immediately

• Patients with known brain metastases or leptomeningeal metastases are excluded unless the following conditions are met:

  • Metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete (must be confirmed within 28 days prior to the first dose of nivolumab administration)
  • There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration

• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

  • Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

• 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, should be excluded; these include but are 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 (IRB), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded; patient 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

  • NOTE: patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if =< 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
• Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, abdominal/pelvic fistula, gastrointestinal perforation, gastrointestinal (GI) obstruction and/or who require parenteral hydration and/or nutrition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (nivolumab); Patients receive nivolumab IV over approximately 60 minutes every 2 weeks for a maximum of 46 doses over 92 weeks in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX-1106; NIVO; ONO-4538; Opdivo; CMAB819; Nivolumab Biosimilar CMAB819; ABP 206; Nivolumab Biosimilar ABP 206; BCD-263; Nivolumab Biosimilar BCD-263

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumor Response as Assessed by RECIST 1.1 Criteria	Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1.	The average of study treatment time was 3.8 months.
Adverse Events (Grade 3 or Higher) During Treatment Period as Assessed by CTCAE Version 4	Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.	Within 100 days of last protocol treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1.	Time from study entry to time of progression or death, whichever occurs first, up to 5 years of follow-up.
Overall Survival	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	Time from study entry to time of death or the date of last contact, up to 5 years of follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Expressions of PD-1 and PD-L1 in Tumor Infiltrating Lymphocytes and Cervical Cancer Cells	Spearman's correlation coefficient will be used to explore the associations of tumor expressions of PD-L1, PD-1 and other interested biomarkers with tumor response. Cox proportional hazards (PH) model will be utilized to evaluate the associations of these tumor expressions with PFS and OS. These expressions may also be dichotomized into high versus low values (cut at the median). Log-rank tests will be used to assess the associations of these dichotomized tumor expressions with PFS and OS. The corresponding hazard rations will be estimated by Cox PH models.	Up to 5 years
Immune Infiltration Related Biomarkers (i.e., CD4+, CD8+, FoxP3) in Tumor Specimens	Immune infiltration related biomarkers (i.e., CD4+, CD8+, FoxP3) in tumor specimens will be associated with objective tumor response, PFS and OS in nivolumab-treated patients.	Up to 5 years
Change in the Immune Response to HPV 16/18/31/35/45 E7 Antigen in Peripheral Blood Lymphocytes and Serum	Wilcoxon signed rank test (for interval or ordinal data) or McNemar's test (for binary data) may be utilized to examine whether the study treatment will change immune response to HPV 16/18/31/35/45 E7 antigen in peripheral blood lymphocytes and serum by changes in the measures of pre- and post-treatment immune response to HPV 16/18/31/35/45 E7.	Baseline to up to 5 years
Change in the CTC Count	Change in the CTC count and whether the CTC count is associated with objective response, PFS and OS in nivolumab-treated patients will be evaluated.	Baseline to up to 12 weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Collaborators: NRG Oncology
• Investigators: Principal Investigator: Alessandro D Santin, NRG Oncology

Publications and helpful links

General Publications

• Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, Khleif S, Lankes HA, Ratner ES, O'Cearbhaill RE, Jazaeri AA, Birrer M. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecol Oncol. 2020 Apr;157(1):161-166. doi: 10.1016/j.ygyno.2019.12.034. Epub 2020 Jan 7.

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2015
• Primary Completion (Actual): March 5, 2019
• Study Completion (Estimated): March 4, 2025

Study Registration Dates

• First Submitted: October 2, 2014
• First Submitted That Met QC Criteria: October 2, 2014
• First Posted (Estimated): October 6, 2014

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Disease Attributes; Neoplasms, Complex and Mixed; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Carcinoma; Recurrence; Carcinoma, Adenosquamous; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: NCI-2014-02021 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180868 (U.S. NIH Grant/Contract); PNRG-GY002_A01PAMDREVW01; NRG-GY002 (Other Identifier: CTEP)