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
Summary
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.
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 Stage II of the study. 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 study treatment, patients are followed up every 12 weeks for 1 year and then every 6 months until 3 years after step 2 registration.
Arms & interventions
- ProcedureBiopsy Procedure
Undergo tumor biopsies
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- DrugCabozantinib S-malate
Given PO
- ProcedureComputed Tomography
Undergo CT scans
- ProcedureMagnetic Resonance Imaging
Undergo MRI scans
- BiologicalNivolumab
Given IV
Outcome measures
Primary
Biomarker results turnaround time
A biomarker turnaround time estimate of at least 75% within 21 days will be considered successful with respect to feasibility. For melanoma participants, turnaround time is defined as the 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. For head and neck squamous cell carcinoma (HNSCC) participants, turnaround time is defined as the time-period between date of tissue submission by the site to central repository and one day after both results have been received by the Southwest Oncology Group Statistics and Data Management Center to simulate when the site would have received notification of participant molecular group determination.
Time frame: Within 21 days
Objective response rate
Confirmed and unconfirmed complete and partial responses) in molecular subgroups. Will assess biomarker response association. To test this association, will consider combination of biomarkers coded as 0 = Lo/Lo, 1 = Lo/Hi or Hi/Lo, and 2 = Hi/Hi. 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). For the melanoma cohort, with approximately equal sized biomarker combination subgroups, a one-sided 0.10 level test for trend using (0,1,2) coding with logistic regression has a power of 80%. The same analysis for HNSCC will have lower power for the same effect size due to the unequal frequencies in the subgroups defined by the biomarkers. We will also conduct disease-by-biomarker interaction tests; however, there will be limited power to detect even to detect relatively large interaction parameters.
Time frame: At the end of stage I
Secondary
Rate and profile of >= grade 3 treatment-related adverse events
Time frame: Up to 2 years
Disease control rate
Time frame: 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
Overall survival
Time frame: 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
Eligibility criteria
Study locations (222)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Tower Cancer Research Foundation
Beverly Hills, California, 90211
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
The Angeles Clinic and Research Institute - West Los Angeles Office
Los Angeles, California, 90025
Cedars-Sinai Medical Center
Los Angeles, California, 90048
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Rocky Mountain Regional VA Medical Center
Aurora, Colorado, 80045
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, 80909
Memorial Hospital North
Colorado Springs, Colorado, 80920
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, 80528
UCHealth Greeley Hospital
Greeley, Colorado, 80631
Medical Center of the Rockies
Loveland, Colorado, 80538
Helen F Graham Cancer Center
Newark, Delaware, 19713
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu, Hawaii, 96813
Queen's Cancer Cenrer - POB I
Honolulu, Hawaii, 96813
Queen's Medical Center
Honolulu, Hawaii, 96813
Queen's Cancer Center - Kuakini
Honolulu, Hawaii, 96817
Hawaii Cancer Care - Westridge
‘Aiea, Hawaii, 96701
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
Saint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, 83301
Rush-Copley Medical Center
Aurora, Illinois, 60504
Illinois CancerCare-Bloomington
Bloomington, Illinois, 61704
Illinois CancerCare-Canton
Canton, Illinois, 61520
Illinois CancerCare-Carthage
Carthage, Illinois, 62321
Centralia Oncology Clinic
Centralia, Illinois, 62801
Northwestern University
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
Carle at The Riverfront
Danville, Illinois, 61832
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois, 60115
Illinois CancerCare-Dixon
Dixon, Illinois, 61021
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Illinois CancerCare-Eureka
Eureka, Illinois, 61530
Illinois CancerCare-Galesburg
Galesburg, Illinois, 61401
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois, 60134
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois, 61443
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois, 60045
Illinois CancerCare-Macomb
Macomb, Illinois, 61455
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Loyola University Medical Center
Maywood, Illinois, 60153
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
Northwestern Medicine Orland Park
Orland Park, Illinois, 60462
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Illinois CancerCare-Pekin
Pekin, Illinois, 61554
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Illinois CancerCare-Peru
Peru, Illinois, 61354
Illinois CancerCare-Princeton
Princeton, Illinois, 61356
Memorial Hospital East
Shiloh, Illinois, 62269
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Springfield Clinic
Springfield, Illinois, 62702
Springfield Memorial Hospital
Springfield, Illinois, 62781
Carle Cancer Center
Urbana, Illinois, 61801
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois, 60555
Illinois CancerCare - Washington
Washington, Illinois, 61571
Rush-Copley Healthcare Center
Yorkville, Illinois, 60560
Mary Greeley Medical Center
Ames, Iowa, 50010
McFarland Clinic - Ames
Ames, Iowa, 50010
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
McFarland Clinic - Boone
Boone, Iowa, 50036
Mercy Hospital
Cedar Rapids, Iowa, 52403
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, 50325
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa, 50501
McFarland Clinic - Jefferson
Jefferson, Iowa, 50129
McFarland Clinic - Marshalltown
Marshalltown, Iowa, 50158
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263
Tufts Medical Center
Boston, Massachusetts, 02111
Baystate Medical Center
Springfield, Massachusetts, 01199
Tufts Medical Center Cancer Center Stoneham
Stoneham, Massachusetts, 02180
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Bronson Battle Creek
Battle Creek, Michigan, 49017
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
OSF Saint Francis Hospital and Medical Group
Escanaba, Michigan, 49829
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, 48334
Cancer Hematology Centers - Flint
Flint, Michigan, 48503
Genesee Hematology Oncology PC
Flint, Michigan, 48503
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, 49503
Trinity Health Grand Rapids Hospital
Grand Rapids, Michigan, 49503
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
West Michigan Cancer Center
Kalamazoo, Michigan, 49007
Beacon Kalamazoo Cancer Center
Kalamazoo, Michigan, 49009
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
Trinity Health Muskegon Hospital
Muskegon, Michigan, 49444
Corewell Health Lakeland Hospitals - Niles Hospital
Niles, Michigan, 49120
Cancer and Hematology Centers of Western Michigan - Norton Shores
Norton Shores, Michigan, 49444
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341
Corewell Health Reed City Hospital
Reed City, Michigan, 49677
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085
Munson Medical Center
Traverse City, Michigan, 49684
University of Michigan Health - West
Wyoming, Michigan, 49519
Huron Gastroenterology PC
Ypsilanti, Michigan, 48106
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota, 56401
Mercy Hospital
Coon Rapids, Minnesota, 55433
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636
Essentia Health Saint Mary's - Detroit Lakes Clinic
Detroit Lakes, Minnesota, 56501
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Fairview Southdale Hospital
Edina, Minnesota, 55435
Essentia Health - Fosston
Fosston, Minnesota, 56542
Unity Hospital
Fridley, Minnesota, 55432
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Essentia Health - Park Rapids
Park Rapids, Minnesota, 56470
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Essentia Health Sandstone
Sandstone, Minnesota, 55072
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792
Ridgeview Medical Center
Waconia, Minnesota, 55387
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital South
St Louis, Missouri, 63128
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Community Hospital of Anaconda
Anaconda, Montana, 59711
Billings Clinic Cancer Center
Billings, Montana, 59101
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Logan Health Medical Center
Kalispell, Montana, 59901
Community Medical Center
Missoula, Montana, 59804
Nebraska Medicine-Bellevue
Bellevue, Nebraska, 68123
Nebraska Medicine-Village Pointe
Omaha, Nebraska, 68118
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Northwell Health/Center for Advanced Medicine
Lake Success, New York, 11042
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, 28328
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, 27534
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, 28546
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota, 58103
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122
Essentia Health - Jamestown Clinic
Jamestown, North Dakota, 58401
Miami Valley Hospital South
Centerville, Ohio, 45459
Premier Blood and Cancer Center
Dayton, Ohio, 45409
Miami Valley Hospital North
Dayton, Ohio, 45415
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066
Miami Valley Cancer Care and Infusion
Greenville, Ohio, 45331
Upper Valley Medical Center
Troy, Ohio, 45373
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Saint Charles Health System
Bend, Oregon, 97701
Clackamas Radiation Oncology Center
Clackamas, Oregon, 97015
Providence Newberg Medical Center
Newberg, Oregon, 97132
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914
Providence Willamette Falls Medical Center
Oregon City, Oregon, 97045
Providence Portland Medical Center
Portland, Oregon, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Jefferson Torresdale Hospital
Philadelphia, Pennsylvania, 19114
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090
Rapid City Regional Hospital
Rapid City, South Dakota, 57701
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Dartmouth Cancer Center - North
Saint Johnsbury, Vermont, 05819
Inova Alexandria Hospital
Alexandria, Virginia, 22304
Inova Schar Cancer Institute
Fairfax, Virginia, 22031
Inova Fair Oaks Hospital
Fairfax, Virginia, 22033
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Centra Alan B Pearson Regional Cancer Center
Lynchburg, Virginia, 24501
Virginia Cancer Institute
Richmond, Virginia, 23229
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
VCU Health Tappahannock Hospital
Tappahannock, Virginia, 22560
Duluth Clinic Ashland
Ashland, Wisconsin, 54806
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, 53149
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, 53066
Saint Vincent Hospital Cancer Center at Oconto Falls
Oconto Falls, Wisconsin, 54154
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868
Saint Vincent Hospital Cancer Center at Sheboygan
Sheboygan, Wisconsin, 53081
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482
Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay, Wisconsin, 54235-1495
Essentia Health Saint Mary's Hospital - Superior
Superior, Wisconsin, 54880
ProHealth Waukesha Memorial Hospital
Waukesha, Wisconsin, 53188
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, 53188
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476