BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study

May 1, 2024 updated by: National Cancer Institute (NCI)

Biomarker Stratified CaboZantinib (NSC#761968) and NivOlumab (NSC#748726) (BiCaZO) - A Phase II Study of Combining Cabozantinib and Nivolumab in Participants With Advanced Solid Tumors (IO Refractory Melanoma or HNSCC) Stratified by Tumor Biomarkers - an immunoMATCH Pilot Study

This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or squamous cell head and neck cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine how quickly patients can be divided into groups based on biomarkers in their tumors. A biomarker is a biological molecule found in the blood, other body fluids, or in tissues that is a sign of a normal or abnormal process or a sign of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. The two biomarkers that this trial is studying are "tumor mutational burden" and "tumor inflammation signature." Another purpose of this trial is to help doctors learn if cabozantinib and nivolumab shrink or stabilize the cancer, and whether patients respond differently to the combination depending on the status of the biomarkers.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of molecular characterization based on tumor mutation burden (TMB) for participant stratification, as assessed by the proportion of participants with less than or equal to a 21-day turnaround time for biopsy results in Stage I of the study.

II. To evaluate the feasibility of molecular characterization based on TMB and gene expression profiling (GEP) (for Tumor Inflammation Score [TIS]) for stratification as assessed by the proportion of participants with less than or equal to a 21-day turnaround time for biopsy results in the overall study (Stage I and Stage II).

III. To evaluate the efficacy by overall response rate (ORR - defined as confirmed and unconfirmed partial responses plus complete responses) of cabozantinib S-malate (cabozantinib) plus nivolumab in each disease cohort, both across and within tumor biomarker subgroups.

SECONDARY OBJECTIVES:

I. To assess the difference in ORR in each disease cohort between tumor marker subgroups separately for each disease cohort.

II. To assess safety and tolerability of this treatment in these populations. III. To estimate disease control rate (DCR) in participants receiving cabozantinib plus nivolumab in each disease cohort, stratified by tumor biomarkers.

IV. To estimate progression-free survival (PFS) in participants receiving cabozantinib plus nivolumab in each disease cohort, stratified by tumor biomarkers.

V. To estimate overall survival (OS) in participants receiving cabozantinib plus nivolumab in each disease cohort, stratified by tumor biomarkers.

VI. To assess the proportion of patients with assay failure, and the time from the date of tissue collection to molecular group determination at the end of Stage I.

ADDITIONAL OBJECTIVE:

I. To identify candidate biomarkers predictive of response and toxicity to the cabozantinib and nivolumab combination.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle and cabozantinib orally (PO) daily. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) scans and collection of blood samples throughout the trial. Patients undergo a tumor biopsy during screening and optionally during follow-up.

After completion of the study treatment, patients are followed for up to 3 years.

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Hospital in Arizona
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
        • Principal Investigator:
          • Arkadiusz Z. Dudek
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • University of Arkansas for Medical Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 501-686-8274
        • Principal Investigator:
          • Omar T. Atiq
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Rocky Mountain Regional VA Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 888-336-8262
        • Principal Investigator:
          • Jessica D. McDermott
      • Colorado Springs, Colorado, United States, 80909
        • Recruiting
        • UCHealth Memorial Hospital Central
        • Contact:
          • Site Public Contact
          • Phone Number: 719-365-2406
        • Principal Investigator:
          • Robert J. Hoyer
      • Colorado Springs, Colorado, United States, 80920
        • Recruiting
        • Memorial Hospital North
        • Contact:
          • Site Public Contact
          • Phone Number: 719-364-6700
        • Principal Investigator:
          • Robert J. Hoyer
      • Fort Collins, Colorado, United States, 80524
        • Recruiting
        • Poudre Valley Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 970-297-6150
        • Principal Investigator:
          • Robert J. Hoyer
      • Fort Collins, Colorado, United States, 80528
        • Recruiting
        • Cancer Care and Hematology-Fort Collins
        • Contact:
        • Principal Investigator:
          • Robert J. Hoyer
      • Greeley, Colorado, United States, 80631
        • Recruiting
        • UCHealth Greeley Hospital
        • Contact:
        • Principal Investigator:
          • Robert J. Hoyer
      • Loveland, Colorado, United States, 80538
        • Recruiting
        • Medical Center of the Rockies
        • Contact:
          • Site Public Contact
          • Phone Number: 970-203-7083
        • Principal Investigator:
          • Robert J. Hoyer
    • Delaware
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Helen F Graham Cancer Center
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Medical Oncology Hematology Consultants PA
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32224-9980
        • Recruiting
        • Mayo Clinic in Florida
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
        • Principal Investigator:
          • Arkadiusz Z. Dudek
    • Idaho
      • Boise, Idaho, United States, 83712
        • Recruiting
        • Saint Luke's Cancer Institute - Boise
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Boise, Idaho, United States, 83706
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Boise
        • Contact:
        • Principal Investigator:
          • John M. Schallenkamp
      • Caldwell, Idaho, United States, 83605
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Caldwell
        • Contact:
        • Principal Investigator:
          • John M. Schallenkamp
      • Coeur d'Alene, Idaho, United States, 83814
        • Recruiting
        • Kootenai Health - Coeur d'Alene
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Fruitland, Idaho, United States, 83619
        • Recruiting
        • Saint Luke's Cancer Institute - Fruitland
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Meridian, Idaho, United States, 83642
        • Recruiting
        • Saint Luke's Cancer Institute - Meridian
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Nampa, Idaho, United States, 83686
        • Recruiting
        • Saint Luke's Cancer Institute - Nampa
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Nampa, Idaho, United States, 83687
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Nampa
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Post Falls, Idaho, United States, 83854
        • Recruiting
        • Kootenai Clinic Cancer Services - Post Falls
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Sandpoint, Idaho, United States, 83864
        • Recruiting
        • Kootenai Cancer Clinic
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Twin Falls, Idaho, United States, 83301
        • Recruiting
        • Saint Luke's Cancer Institute - Twin Falls
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
    • Illinois
      • Aurora, Illinois, United States, 60504
        • Recruiting
        • Rush - Copley Medical Center
        • Contact:
        • Principal Investigator:
          • Prem Sobti
      • Bloomington, Illinois, United States, 61704
        • Recruiting
        • Illinois CancerCare-Bloomington
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Canton, Illinois, United States, 61520
        • Recruiting
        • Illinois CancerCare-Canton
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Carthage, Illinois, United States, 62321
        • Recruiting
        • Illinois CancerCare-Carthage
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Centralia, Illinois, United States, 62801
        • Recruiting
        • Centralia Oncology Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:
        • Principal Investigator:
          • Jeffrey A. Sosman
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois
        • Contact:
          • Site Public Contact
          • Phone Number: 312-355-3046
        • Principal Investigator:
          • Ryan Nguyen
      • Danville, Illinois, United States, 61832
        • Recruiting
        • Carle at The Riverfront
        • Contact:
        • Principal Investigator:
          • Prem Sobti
      • DeKalb, Illinois, United States, 60115
        • Recruiting
        • Northwestern Medicine Cancer Center Kishwaukee
        • Contact:
        • Principal Investigator:
          • Jeffrey A. Sosman
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Decatur Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Dixon, Illinois, United States, 61021
        • Recruiting
        • Illinois CancerCare-Dixon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 815-285-7800
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Carle Physician Group-Effingham
        • Contact:
        • Principal Investigator:
          • Prem Sobti
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Crossroads Cancer Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Eureka, Illinois, United States, 61530
        • Recruiting
        • Illinois CancerCare-Eureka
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Galesburg, Illinois, United States, 61401
        • Recruiting
        • Illinois CancerCare-Galesburg
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Geneva, Illinois, United States, 60134
        • Recruiting
        • Northwestern Medicine Cancer Center Delnor
        • Contact:
        • Principal Investigator:
          • Jeffrey A. Sosman
      • Kewanee, Illinois, United States, 61443
        • Recruiting
        • Illinois CancerCare-Kewanee Clinic
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Lake Forest, Illinois, United States, 60045
        • Recruiting
        • Northwestern Medicine Lake Forest Hospital
        • Contact:
        • Principal Investigator:
          • Jeffrey A. Sosman
      • Macomb, Illinois, United States, 61455
        • Recruiting
        • Illinois CancerCare-Macomb
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Mattoon, Illinois, United States, 61938
        • Recruiting
        • Carle Physician Group-Mattoon/Charleston
        • Contact:
        • Principal Investigator:
          • Prem Sobti
      • O'Fallon, Illinois, United States, 62269
        • Recruiting
        • Cancer Care Center of O'Fallon
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Ottawa, Illinois, United States, 61350
        • Recruiting
        • Illinois CancerCare-Ottawa Clinic
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Pekin, Illinois, United States, 61554
        • Recruiting
        • Illinois CancerCare-Pekin
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Peoria, Illinois, United States, 61615
        • Recruiting
        • Illinois CancerCare-Peoria
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Peru, Illinois, United States, 61354
        • Recruiting
        • Illinois CancerCare-Peru
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Princeton, Illinois, United States, 61356
        • Recruiting
        • Illinois CancerCare-Princeton
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Southern Illinois University School of Medicine
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 217-545-7929
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Springfield Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 800-444-7541
      • Springfield, Illinois, United States, 62781
        • Recruiting
        • Memorial Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Prem Sobti
      • Warrenville, Illinois, United States, 60555
        • Recruiting
        • Northwestern Medicine Cancer Center Warrenville
        • Contact:
        • Principal Investigator:
          • Jeffrey A. Sosman
      • Washington, Illinois, United States, 61571
        • Recruiting
        • Illinois CancerCare - Washington
        • Contact:
        • Principal Investigator:
          • Bryan A. Faller
      • Yorkville, Illinois, United States, 60560
        • Recruiting
        • Rush-Copley Healthcare Center
        • Contact:
        • Principal Investigator:
          • Prem Sobti
    • Iowa
      • Ames, Iowa, United States, 50010
        • Recruiting
        • Mary Greeley Medical Center
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Ames, Iowa, United States, 50010
        • Recruiting
        • McFarland Clinic - Ames
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
      • Ankeny, Iowa, United States, 50023
        • Recruiting
        • Mission Cancer and Blood - Ankeny
        • Principal Investigator:
          • Richard L. Deming
        • Contact:
          • Site Public Contact
          • Phone Number: 515-282-2921
      • Boone, Iowa, United States, 50036
        • Recruiting
        • McFarland Clinic - Boone
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Cedar Rapids, Iowa, United States, 52403
        • Recruiting
        • Mercy Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 319-365-4673
        • Principal Investigator:
          • Deborah W. Wilbur
      • Cedar Rapids, Iowa, United States, 52403
        • Recruiting
        • Oncology Associates at Mercy Medical Center
        • Principal Investigator:
          • Deborah W. Wilbur
        • Contact:
          • Site Public Contact
          • Phone Number: 319-363-2690
      • Clive, Iowa, United States, 50325
        • Recruiting
        • Medical Oncology and Hematology Associates-West Des Moines
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Richard L. Deming
      • Clive, Iowa, United States, 50325
        • Recruiting
        • Mercy Cancer Center-West Lakes
        • Principal Investigator:
          • Richard L. Deming
        • Contact:
      • Des Moines, Iowa, United States, 50309
        • Recruiting
        • Medical Oncology and Hematology Associates-Des Moines
        • Principal Investigator:
          • Joshua Lukenbill
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
      • Des Moines, Iowa, United States, 50314
        • Recruiting
        • Mercy Medical Center - Des Moines
        • Principal Investigator:
          • Richard L. Deming
        • Contact:
      • Des Moines, Iowa, United States, 50314
        • Recruiting
        • Mission Cancer and Blood - Laurel
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Richard L. Deming
      • Fort Dodge, Iowa, United States, 50501
        • Recruiting
        • McFarland Clinic - Trinity Cancer Center
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Jefferson, Iowa, United States, 50129
        • Recruiting
        • McFarland Clinic - Jefferson
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
      • Marshalltown, Iowa, United States, 50158
        • Recruiting
        • McFarland Clinic - Marshalltown
        • Principal Investigator:
          • Joseph J. Merchant
        • Contact:
          • Site Public Contact
          • Phone Number: 515-956-4132
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
      • Springfield, Massachusetts, United States, 01199
        • Recruiting
        • Baystate Medical Center
        • Contact:
        • Principal Investigator:
          • John C. McCann
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-865-1125
        • Principal Investigator:
          • Paul L. Swiecicki
      • Battle Creek, Michigan, United States, 49017
        • Recruiting
        • Bronson Battle Creek
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Brighton, Michigan, United States, 48114
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Canton, Michigan, United States, 48188
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Chelsea, Michigan, United States, 48118
      • Chelsea, Michigan, United States, 48118
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Wayne State University/Karmanos Cancer Institute
        • Contact:
        • Principal Investigator:
          • Ammar Sukari
      • Farmington Hills, Michigan, United States, 48334
        • Recruiting
        • Weisberg Cancer Treatment Center
        • Contact:
        • Principal Investigator:
          • Ammar Sukari
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Cancer and Blood Disease Treatment Center
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Hematology Oncology PC
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesys Hurley Cancer Institute
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Hurley Medical Center
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Spectrum Health at Butterworth Campus
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Trinity Health Grand Rapids Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Kalamazoo, Michigan, United States, 49007
        • Recruiting
        • Bronson Methodist Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Kalamazoo, Michigan, United States, 49007
        • Recruiting
        • West Michigan Cancer Center
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Kalamazoo, Michigan, United States, 49009
        • Recruiting
        • Ascension Borgess Cancer Center
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Lansing, Michigan, United States, 48912
        • Recruiting
        • University of Michigan Health - Sparrow Lansing
        • Principal Investigator:
          • Elie G. Dib
        • Contact:
      • Livonia, Michigan, United States, 48154
        • Recruiting
        • Trinity Health Saint Mary Mercy Livonia Hospital
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
      • Muskegon, Michigan, United States, 49444
        • Recruiting
        • Trinity Health Muskegon Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Norton Shores, Michigan, United States, 49444
        • Recruiting
        • Cancer and Hematology Centers of Western Michigan - Norton Shores
        • Principal Investigator:
          • Kathleen J. Yost
        • Contact:
      • Reed City, Michigan, United States, 49677
        • Recruiting
        • Corewell Health Reed City Hospital
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Saint Joseph, Michigan, United States, 49085
        • Recruiting
        • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Traverse City, Michigan, United States, 49684
        • Recruiting
        • Munson Medical Center
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Wyoming, Michigan, United States, 49519
        • Recruiting
        • University of Michigan Health - West
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Ypsilanti, Michigan, United States, 48106
      • Ypsilanti, Michigan, United States, 48197
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
        • Contact:
        • Principal Investigator:
          • Elie G. Dib
    • Minnesota
      • Bemidji, Minnesota, United States, 56601
      • Brainerd, Minnesota, United States, 56401
        • Recruiting
        • Essentia Health Saint Joseph's Medical Center
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Coon Rapids, Minnesota, United States, 55433
        • Recruiting
        • Mercy Hospital
        • Contact:
        • Principal Investigator:
          • David M. King
      • Deer River, Minnesota, United States, 56636
        • Recruiting
        • Essentia Health - Deer River Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Detroit Lakes, Minnesota, United States, 56501
        • Recruiting
        • Essentia Health Saint Mary's - Detroit Lakes Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Duluth, Minnesota, United States, 55805
        • Recruiting
        • Essentia Health Cancer Center
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Edina, Minnesota, United States, 55435
        • Recruiting
        • Fairview Southdale Hospital
        • Contact:
        • Principal Investigator:
          • David M. King
      • Fosston, Minnesota, United States, 56542
        • Recruiting
        • Essentia Health - Fosston
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Fridley, Minnesota, United States, 55432
        • Active, not recruiting
        • Unity Hospital
      • Hibbing, Minnesota, United States, 55746
        • Recruiting
        • Essentia Health Hibbing Clinic
        • Principal Investigator:
          • Bret E. Friday
        • Contact:
          • Site Public Contact
          • Phone Number: 218-786-3308
      • Minneapolis, Minnesota, United States, 55407
        • Recruiting
        • Abbott-Northwestern Hospital
        • Contact:
        • Principal Investigator:
          • David M. King
      • Park Rapids, Minnesota, United States, 56470
        • Recruiting
        • Essentia Health - Park Rapids
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
        • Principal Investigator:
          • Arkadiusz Z. Dudek
      • Saint Louis Park, Minnesota, United States, 55416
        • Recruiting
        • Park Nicollet Clinic - Saint Louis Park
        • Contact:
        • Principal Investigator:
          • David M. King
      • Saint Paul, Minnesota, United States, 55101
        • Recruiting
        • Regions Hospital
        • Contact:
        • Principal Investigator:
          • David M. King
      • Saint Paul, Minnesota, United States, 55102
        • Recruiting
        • United Hospital
        • Contact:
        • Principal Investigator:
          • David M. King
      • Sandstone, Minnesota, United States, 55072
        • Recruiting
        • Essentia Health Sandstone
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Virginia, Minnesota, United States, 55792
        • Recruiting
        • Essentia Health Virginia Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Woodbury, Minnesota, United States, 55125
        • Recruiting
        • Minnesota Oncology Hematology PA-Woodbury
        • Contact:
        • Principal Investigator:
          • David M. King
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Recruiting
        • Saint Francis Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 573-334-2230
          • Email: sfmc@sfmc.net
    • Montana
      • Anaconda, Montana, United States, 59711
        • Recruiting
        • Community Hospital of Anaconda
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Billings, Montana, United States, 59101
        • Recruiting
        • Billings Clinic Cancer Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Bozeman, Montana, United States, 59715
        • Recruiting
        • Bozeman Deaconess Hospital
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Great Falls, Montana, United States, 59405
        • Recruiting
        • Benefis Healthcare- Sletten Cancer Institute
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Kalispell, Montana, United States, 59901
        • Recruiting
        • Kalispell Regional Medical Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Missoula, Montana, United States, 59804
        • Recruiting
        • Community Medical Hospital
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
    • Nebraska
      • Bellevue, Nebraska, United States, 68123
        • Recruiting
        • Nebraska Medicine-Bellevue
        • Contact:
        • Principal Investigator:
          • Alissa S. Marr
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:
        • Principal Investigator:
          • Alissa S. Marr
      • Omaha, Nebraska, United States, 68118
        • Recruiting
        • Nebraska Medicine-Village Pointe
        • Contact:
          • Site Public Contact
          • Phone Number: 402-559-5600
        • Principal Investigator:
          • Alissa S. Marr
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Recruiting
        • University of New Mexico Cancer Center
        • Contact:
        • Principal Investigator:
          • Moises Harari-Turquie
    • New York
      • Lake Success, New York, United States, 11042
        • Active, not recruiting
        • Northwell Health/Center for Advanced Medicine
    • North Carolina
      • Clinton, North Carolina, United States, 28328
        • Recruiting
        • Southeastern Medical Oncology Center-Clinton
        • Contact:
        • Principal Investigator:
          • Samer S. Kasbari
      • Goldsboro, North Carolina, United States, 27534
        • Recruiting
        • Southeastern Medical Oncology Center-Goldsboro
        • Contact:
        • Principal Investigator:
          • Samer S. Kasbari
      • Jacksonville, North Carolina, United States, 28546
        • Recruiting
        • Southeastern Medical Oncology Center-Jacksonville
        • Principal Investigator:
          • Samer S. Kasbari
        • Contact:
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
      • Fargo, North Dakota, United States, 58122
      • Fargo, North Dakota, United States, 58103
        • Recruiting
        • Essentia Health Cancer Center-South University Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Fargo, North Dakota, United States, 58122
      • Jamestown, North Dakota, United States, 58401
        • Recruiting
        • Essentia Health - Jamestown Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
    • Ohio
      • Centerville, Ohio, United States, 45459
        • Recruiting
        • Miami Valley Hospital South
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45415
        • Recruiting
        • Miami Valley Hospital North
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45409
        • Recruiting
        • Dayton Blood and Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 937-276-8320
        • Principal Investigator:
          • Tarek M. Sabagh
      • Franklin, Ohio, United States, 45005-1066
        • Recruiting
        • Atrium Medical Center-Middletown Regional Hospital
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Greenville, Ohio, United States, 45331
        • Recruiting
        • Miami Valley Cancer Care and Infusion
        • Principal Investigator:
          • Tarek M. Sabagh
        • Contact:
          • Site Public Contact
          • Phone Number: 937-569-7515
      • Troy, Ohio, United States, 45373
        • Recruiting
        • Upper Valley Medical Center
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Minh Phan
    • Oregon
      • Bend, Oregon, United States, 97701
        • Recruiting
        • Saint Charles Health System
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Clackamas, Oregon, United States, 97015
        • Recruiting
        • Clackamas Radiation Oncology Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Newberg, Oregon, United States, 97132
        • Recruiting
        • Providence Newberg Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Ontario, Oregon, United States, 97914
        • Recruiting
        • Saint Alphonsus Medical Center-Ontario
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Oregon City, Oregon, United States, 97045
        • Recruiting
        • Providence Willamette Falls Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
      • Portland, Oregon, United States, 97225
        • Recruiting
        • Providence Saint Vincent Medical Center
        • Contact:
        • Principal Investigator:
          • Charles W. Drescher
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Hospital
        • Contact:
        • Principal Investigator:
          • Jennifer M. Johnson
      • Philadelphia, Pennsylvania, United States, 19114
        • Recruiting
        • Jefferson Torresdale Hospital
        • Contact:
        • Principal Investigator:
          • Jennifer M. Johnson
      • Willow Grove, Pennsylvania, United States, 19090
        • Recruiting
        • Asplundh Cancer Pavilion
        • Contact:
        • Principal Investigator:
          • Jennifer M. Johnson
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
      • Sioux Falls, South Dakota, United States, 57117-5134
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute/University of Utah
        • Contact:
        • Principal Investigator:
          • Jeffery S. Russell
    • Virginia
      • Alexandria, Virginia, United States, 22304
        • Recruiting
        • Inova Alexandria Hospital
        • Contact:
        • Principal Investigator:
          • Sekwon Jang
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Inova Schar Cancer Institute
        • Contact:
        • Principal Investigator:
          • Sekwon Jang
      • Fairfax, Virginia, United States, 22033
        • Recruiting
        • Inova Fair Oaks Hospital
        • Contact:
        • Principal Investigator:
          • Sekwon Jang
      • Falls Church, Virginia, United States, 22042
        • Recruiting
        • Inova Fairfax Hospital
        • Contact:
        • Principal Investigator:
          • Sekwon Jang
      • Lynchburg, Virginia, United States, 24501
        • Recruiting
        • Centra Lynchburg Hematology-Oncology Clinic Inc
        • Principal Investigator:
          • Andrew Poklepovic
        • Contact:
      • Richmond, Virginia, United States, 23229
        • Recruiting
        • Virginia Cancer Institute
        • Contact:
        • Principal Investigator:
          • Andrew Poklepovic
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University/Massey Cancer Center
        • Contact:
        • Principal Investigator:
          • Andrew Poklepovic
      • Richmond, Virginia, United States, 23235
        • Recruiting
        • VCU Massey Cancer Center at Stony Point
        • Contact:
        • Principal Investigator:
          • Andrew Poklepovic
    • Wisconsin
      • Ashland, Wisconsin, United States, 54806
        • Recruiting
        • Duluth Clinic Ashland
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • La Crosse, Wisconsin, United States, 54601
        • Recruiting
        • Gundersen Lutheran Medical Center
        • Contact:
        • Principal Investigator:
          • David E. Marinier
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Principal Investigator:
          • Callisia N. Clarke
        • Contact:
          • Site Public Contact
          • Phone Number: 414-805-3666
      • Minocqua, Wisconsin, United States, 54548
      • Mukwonago, Wisconsin, United States, 53149
        • Recruiting
        • ProHealth D N Greenwald Center
        • Contact:
        • Principal Investigator:
          • Timothy R. Wassenaar
      • Oconomowoc, Wisconsin, United States, 53066
        • Recruiting
        • ProHealth Oconomowoc Memorial Hospital
        • Principal Investigator:
          • Timothy R. Wassenaar
        • Contact:
          • Site Public Contact
          • Phone Number: 262-928-7878
      • Superior, Wisconsin, United States, 54880
        • Recruiting
        • Essentia Health Saint Mary's Hospital - Superior
        • Principal Investigator:
          • Bret E. Friday
        • Contact:
          • Site Public Contact
          • Phone Number: 701-364-6272
      • Waukesha, Wisconsin, United States, 53188
        • Recruiting
        • ProHealth Waukesha Memorial Hospital
        • Principal Investigator:
          • Timothy R. Wassenaar
        • Contact:
          • Site Public Contact
          • Phone Number: 262-928-7632
      • Waukesha, Wisconsin, United States, 53188
        • Recruiting
        • UW Cancer Center at ProHealth Care
        • Principal Investigator:
          • Timothy R. Wassenaar
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • STEP 1 - SPECIMEN SUBMISSION

  • Participants must have histologically confirmed melanoma that is stage III or IV, unresectable, recurrent, or metastatic non-uveal melanoma OR Participants must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) that is either locally recurrent and non-amendable to curative therapy (e.g., radiation, surgery) or metastatic. The primary tumor location must be the oropharynx, oral cavity, hypopharynx, or larynx. Primary tumor site of nasopharynx (any histology) or unknown primary tumor are not eligible

    • Note: For participants with primary oropharyngeal cancer, human papillomavirus (HPV) or p16 status must be known prior to step 1 registration
  • Participants must have disease presentation consistent with measurable disease. Note: Current disease measurements will not be required until step 2 registration
  • Participants must have had documented progression within 12 weeks after the last dose of PD-1 checkpoint inhibition-based therapy. Participants must have been receiving checkpoint inhibition for a minimum of 6 weeks. Participants who recur during adjuvant anti-PD1 treatment or within 12 weeks of completion of adjuvant anti-PD1 treatment are eligible if they have measurable disease and are considered unresectable
  • Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test within 6 months prior to step 1 registration
  • Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load within 28 days prior to step 1 registration
  • Participants with a history of hepatitis C virus (HCV) infection must have no detectable viral load within 28 days prior to step 1 registration
  • Participants must not have an active infection requiring systemic therapy (except HBV, HCV or HIV as mentioned above)
  • Participants must not have known history of congenital long QT syndrome and must not have experienced unstable angina pectoris, clinically significant cardiac arrhythmias, or stroke (transient ischemic attack [TIA] or other ischemic event) within 90 days prior to Step 1 registration
  • Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days prior to step 1 registration, unless clinically stable with ongoing medical management
  • Participants must have recovered to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 toxicities related to any prior treatments, unless adverse events are deemed clinically nonsignificant by the treating investigator or stable on supportive therapy

  • Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to the mucosal surfaces of the head and neck, with the additional following criteria:

    • If the primary radiation is combined with chemotherapy, a minimum of 16 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration. If the radiation is given alone, a minimum of 8 weeks will be required to have elapsed between the end of radiotherapy and step 1 registration
    • Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) with the exception of central nervous system (CNS) radiation and must be completed at least 4 weeks prior to step 1 registration
    • Treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation
  • Participants must not have received prior treatment with anti-VEGF therapies for any reason
  • Participants must be >= 18 years of age
  • Participants must have a Zubrod Performance Status 0 or 1
  • Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and must be class 2B or better to be eligible for this trial
  • Participants must not have any known significant organ disfunction that, in the opinion of the treating investigator, may impact suitability for receiving combination nivolumab/cabozantinib treatment
  • Participants must be able to take oral medication without breaking, opening, crushing, dissolving or chewing capsules
  • Participants must not have malabsorption syndrome

  • Participants must not have active autoimmune disease requiring systemic steroids (equivalent of > 10mg of prednisone) or other immune suppression. Exceptions:

    • Type 1 diabetes mellitus
    • Endocrinopathy only requiring hormone replacement
    • Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment
    • Conditions not expected to recur in the absence of an external trigger
  • Participants must not have received an organ allograft
  • Participants must not have a history of hemoptysis (defined as >= 1/2 tsp of bright red blood per day) or tumor bleeding within 90 days prior to step 1 registration

  • Participants must not have any of the following criteria due to the possibility of increased risk for tumor bleeding with cabozantinib therapy:

    • Prior carotid bleeding
    • Tumors that invade major vessels (e.g., the carotid) as shown unequivocally by imaging studies
    • Central (e.g., within 2 cm from the hilum) lung metastases that are cavitary as shown unequivocally by imaging studies
    • Any prior history of bleeding related to the current head and neck cancer
    • History of gross hemoptysis (bright red blood of 1/2 teaspoon or more per episode of coughing) within 3 months

  • Participants must not require concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)

    • Participants must not require anticoagulants except for the following:

      • Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
      • Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors, rivaroxaban, edoxaban, or apixaban in participants without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to step 1 registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
  • Participants must not have evidence of preexisting uncontrolled hypertension 28 days prior to step 1 registration as documented by baseline blood pressure reading with systolic blood pressure >= 150 mmHg and/or diastolic blood pressure >= 90 mmHg. Participants on antihypertensive therapies with controlled blood pressure are eligible
  • Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • Participants must not be pregnant or nursing due to the known safety profiles of the drugs in this study. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential. In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion and vasectomy with testing showing no sperm in the semen
  • Have an adequate archival tissue specimen verified by the local pathologist and documented on the Pathology Review Form from a procedure obtained after the development of resistance to anti-PD-1/L1 therapy. Archival tissue must consist of tumor block or at least 1 H&E-stained 4-5 micron slide and 20 freshly cut serially sectioned and numbered 4-5 micron unstained, uncharged slides OR

Be willing to undergo research biopsy AND have tumor accessible for biopsy based on the following criteria:

  • Mediastinal, laparoscopic, gastrointestinal, or bronchial endoscopic biopsies can be obtained incidentally to a clinically necessary procedure and NOT for the sole purpose of the clinical trial

  • Acceptable biopsy procedures are:

    • Percutaneous biopsy with local anesthetic and/or sedation with an expected risk of severe complications < 2%
    • Direct transoral biopsy (with or without local anesthetic and/or sedation) with an expected risk of severe complications < 2%
    • Excisional cutaneous biopsy with local anesthetic and/or sedation with an expected risk of severe complications < 2%
    • Biopsy with removal of additional tumor tissue during a medically necessary mediastinoscopy, laparoscopy, gastrointestinal endoscopy, bronchoscopy or craniotomy. No open surgical, laparoscopic or endoscopic procedure should be performed solely to obtain a biopsy for this protocol

    • Removal of additional tumor tissue during a medically necessary surgical procedure

      • Participants must submit whole blood for germline genomic analysis
      • Participants must have been offered the opportunity to participate in specimen banking
      • Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

  • Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator)

    • STEP 2 TREATMENT REGISTRATION

  • Note: No tests or exams are required to be repeated for Step 2 registration (Treatment). However, participants who are known to have a change in eligibility status after Step 1 registration are not eligible for Step 2 registration

    • Participants must have been eligible for step 1 registration continue to meet eligibility for step 1 registration prior to step 2 registration.
    • Participants must have had their tumor tissue submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System prior to step 2 registration
    • Participants registered during stage II of the protocol must have received assignment to an open cohort from the SWOG Statistics and Data Management Center based on their biomarker screening profile (not applicable for patients registered during stage I of the protocol)
    • Participants must have measurable disease. All measurable disease must be assessed within 28 days prior to step 2 registration. All non-measurable disease must be assessed within 42 days prior to step 2 registration. Note: All disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)
    • For melanoma participants, CT chest, abdomen and pelvis must be obtained. For HNSCC participants, CT neck and chest must be obtained. Further imaging (i.e., MR brain, CT abdomen/pelvis or extremities, bone scan) will be performed as deemed appropriate by the treating physician
    • Participants with treated brain metastases must have no evidence of progression on the follow-up brain imaging after central nervous system (CNS)-directed therapy
    • Participants must not have experienced any significant health changes that, in the opinion of the treating investigator, may impact continued suitability for receiving combination nivolumab/cabozantinib treatment
    • Participants with treated brain metastases must have discontinued steroid treatment at least 14 days prior to step 2 registration
    • Participants must not have received investigational agents or monoclonal antibodies (except Food and Drug Administration [FDA] approved supportive care antibodies, such as denosumab) within 28 days prior to step 2 registration
    • Participants must not have received surgery, chemotherapy, radiation therapy, biologic agents, or steroids within 14 days prior to step 2 registration.
    • Participants must not have received administration of a live, attenuated vaccine within 30 days prior to step 2 registration. Note: Participants may have received a messenger ribonucleic acid (mRNA) or viral vector-based coronavirus disease 2019 (COVID-19) vaccine within 30 days prior to step 2 registration
    • Participants must not have received administration of any strong CYP3A4 inducers, such as but not limited to rifampin, carbamazepine, enzalutamide, mitotane, phenytoin and St. John's wort, within 14 days prior to step 2 registration
    • Participants must not have received administration of any strong CYP3A4 inhibitors, such as but not limited to clarithromycin, itraconazole, ketoconazole, grapefruit juice, indinavir, nelfinavir, ritonavir, nefazodone, saquinavir, and telithromycin, within 5 times the half-life of the CYP3A inhibitor prior to step 2 registration
    • Participants must have a history and physical examination performed within 28 days prior to step 2 registration
    • Leukocytes >= 3,000/uL (within 28 days prior to step 2 registration)
    • Absolute neutrophil count >= 1,500/uL (within 28 days prior to step 2 registration)
    • Platelets >= 100,000/uL (within 28 days prior to step 2 registration)
    • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) or =< 3 x ULN for participants with Gilbert's disease (within 28 days prior to step 2 registration)
    • Aspartate aminotransferase (AST) =< 3 x institutional ULN (within 28 days prior to step 2 registration)
    • Alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to step 2 registration)
    • Urinalysis: For baseline value (no required value for eligibility)
    • Measured (OR calculated) creatinine clearance >= 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to step 2 registration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (nivolumab and cabozantinib)
Patients receive nivolumab IV over 30 minutes on day 1 of each cycle and cabozantinib PO daily. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI scans and collection of blood samples throughout the trial. Patients undergo a tumor biopsy during screening and optionally during follow-up.
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
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Drug: Cabozantinib S-malate
Given PO
Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL-184
  • XL184
Procedure: Biopsy
Undergo tumor biopsies
Other Names:
  • Bx
  • BIOPSY_TYPE
Procedure: Computed Tomography
Undergo CT scans
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Procedure: Magnetic Resonance Imaging
Undergo MRI scans
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarker results turnaround time
Time Frame: Time-period between date of tissue submission by the site to central repository and date the site was sent notification of participant molecular group determination, assessed within 21 days
A biomarker turnaround time estimate of at least 75% within 21 days will be considered successful with respect to feasibility.
Time-period between date of tissue submission by the site to central repository and date the site was sent notification of participant molecular group determination, assessed within 21 days
Objective response rate
Time Frame: At the end of stage I
Confirmed and unconfirmed complete and partial responses) in molecular subgroups. Assume each biomarker level is associated with an odds-ratio of approximately 3.1 (for example, corresponding to a difference in response rate of 5 percent to 14 percent from Lo/Lo to Lo/Hi or Hi/Lo). A one-sided .10 level test for trend using (0,1,2) coding above with logistic regression has a power of 80 percent. We will also consider biomarker trend analysis adjusting for disease types. We will also conduct disease-by-biomarker interaction tests; however, there will be limited power even to detect relatively large interaction parameters.
At the end of stage I

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate and profile of >= grade 3 treatment-related adverse events
Time Frame: Up to 2 years
Per Common Terminology Criteria for Adverse Events 5.0. With respect to overall disease group, 60 participants are sufficient to estimate the probability of a particular toxicity to within +/- 13 percent. Any toxicity occurring with at least a 5 percent probability is likely to be seen at least once (95 percent chance).
Up to 2 years
Disease control rate
Time Frame: Up to 2 years
Will be estimated using the method of Kaplan-Meier.
Up to 2 years
Progression-free survival
Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years
Will be estimated using the method of Kaplan-Meier.
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 2 years
Overall survival
Time Frame: From date of registration to date of death due to any cause, assessed up to 2 years
Will be estimated using the method of Kaplan-Meier.
From date of registration to date of death due to any cause, assessed up to 2 years
Turnaround time for the Tumor Inflammation Score in stage II
Time Frame: Assessed within 21 days
Assessed within 21 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Additional markers of response or resistance
Time Frame: Up to 2 years
Explore additional markers of response or resistance through hypothesis generating analysis.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Siwen Hu-Lieskovan, SWOG Cancer Research Network

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 6, 2022

Primary Completion (Estimated)

September 1, 2024

Study Completion (Estimated)

September 1, 2024

Study Registration Dates

First Submitted

November 25, 2021

First Submitted That Met QC Criteria

November 25, 2021

First Posted (Actual)

November 29, 2021

Study Record Updates

Last Update Posted (Actual)

May 2, 2024

Last Update Submitted That Met QC Criteria

May 1, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2021-12653 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180888 (U.S. NIH Grant/Contract)
  • S2101 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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