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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

Primary Purpose

Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8

Status
Suspended
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Biopsy
Biospecimen Collection
Cabozantinib S-malate
Computed Tomography
Magnetic Resonance Imaging
Nivolumab
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clinical Stage III Cutaneous Melanoma AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • STEP 1 - SPECIMEN SUBMISSION INCLUSION CRITERIA
  • 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 prior to progression. 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 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 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 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
  • Have adequate tissue specimen from procedure obtained within 6 months prior to step 1 registration and after development of resistance to anti-PD-1/L1 therapy. Archival tissue must consist of tumor block or at least 20 freshly cut serially sectioned and numbered 4-5 micron unstained, positively-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 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 INCLUSION CRITERIA
    • Participants must have been eligible for step 1 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, computed tomography (CT) chest, abdomen and pelvis must be obtained. For HNSCC participants, CT neck and chest must be obtained. Further imaging (i.e., magnetic resonance imaging [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 with treated brain metastases must have discontinued steroid treatment at least 14 days prior to step 2 registration
    • Participants must have a history and physical examination performed within 28 days prior to step 2 registration
    • Participants must be able to take oral medication without breaking, opening, crushing, dissolving or chewing capsules
    • 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)
    • Fridericia corrected QT interval (QTcF) =< 470 milliseconds on screening electrocardiogram (ECG) (within 28 days prior to step 2 registration)
    • Creatinine =< 3 x institutional ULN OR 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

Exclusion Criteria:

  • STEP 1 - SPECIMEN SUBMISSION EXCLUSION CRITERIA
  • Participants must not have an active infection requiring systemic therapy (except HBV, HCV or HIV as mentioned above)
  • Participants must not have received surgery, chemotherapy, radiation therapy, biologic agents, or steroids within 14 days prior to step 1 registration
  • Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to 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) 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 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 not have active autoimmune disease requiring systemic steroids (equivalent of > 10mg of prednisone) or other immune suppression. Exceptions:

    • Type 1 diabetes mellitus
    • Hypothyroidism 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 known central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (e.g., carotid artery)
  • 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 prior to step 1 registration as documented by 2 baseline blood pressure readings taken at least 30 minutes apart within 28 days prior to step 1 registration. The baseline systolic blood pressure readings must be =< 150 mmHg and the baseline diastolic blood pressure readings must be =< 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
  • STEP 2 TREATMENT REGISTRATION EXCLUSION CRITERIA
  • 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 must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to the head and neck, with the additional following conditions:

    • 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 2 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 2 registration
    • Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) and must be completed at least 4 weeks prior to step 2 registration
    • Treatment areas should be healed with no sequelae from RT that would predispose to fistula formation
  • 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 any prior treatment with anti-VEGF based therapies
  • 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 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 not have malabsorption syndrome
  • Participants must not have central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (e.g., carotid artery)

Sites / Locations

  • University of Arkansas for Medical Sciences
  • Rocky Mountain Regional VA Medical Center
  • UCHealth Memorial Hospital Central
  • Memorial Hospital North
  • Poudre Valley Hospital
  • Cancer Care and Hematology-Fort Collins
  • UCHealth Greeley Hospital
  • Medical Center of the Rockies
  • Helen F Graham Cancer Center
  • Medical Oncology Hematology Consultants PA
  • Mayo Clinic in Florida
  • Saint Alphonsus Cancer Care Center-Boise
  • Saint Luke's Cancer Institute - Boise
  • Saint Alphonsus Cancer Care Center-Caldwell
  • Kootenai Health - Coeur d'Alene
  • Saint Luke's Cancer Institute - Fruitland
  • Saint Luke's Cancer Institute - Meridian
  • Saint Luke's Cancer Institute - Nampa
  • Saint Alphonsus Cancer Care Center-Nampa
  • Kootenai Clinic Cancer Services - Post Falls
  • Kootenai Cancer Clinic
  • Saint Luke's Cancer Institute - Twin Falls
  • Rush - Copley Medical Center
  • Illinois CancerCare-Bloomington
  • Illinois CancerCare-Canton
  • Illinois CancerCare-Carthage
  • Centralia Oncology Clinic
  • Northwestern University
  • Carle at The Riverfront
  • Cancer Care Specialists of Illinois - Decatur
  • Decatur Memorial Hospital
  • Northwestern Medicine Cancer Center Kishwaukee
  • Illinois CancerCare-Dixon
  • Carle Physician Group-Effingham
  • Crossroads Cancer Center
  • Illinois CancerCare-Eureka
  • Illinois CancerCare-Galesburg
  • Northwestern Medicine Cancer Center Delnor
  • Illinois CancerCare-Kewanee Clinic
  • Northwestern Medicine Lake Forest Hospital
  • Illinois CancerCare-Macomb
  • Carle Physician Group-Mattoon/Charleston
  • Cancer Care Center of O'Fallon
  • Illinois CancerCare-Ottawa Clinic
  • Illinois CancerCare-Pekin
  • Illinois CancerCare-Peoria
  • Illinois CancerCare-Peru
  • Illinois CancerCare-Princeton
  • Southern Illinois University School of Medicine
  • Springfield Clinic
  • Memorial Medical Center
  • Carle Cancer Center
  • Northwestern Medicine Cancer Center Warrenville
  • Illinois CancerCare - Washington
  • Rush-Copley Healthcare Center
  • Mary Greeley Medical Center
  • McFarland Clinic - Ames
  • McFarland Clinic - Boone
  • Mercy Hospital
  • Oncology Associates at Mercy Medical Center
  • Medical Oncology and Hematology Associates-Des Moines
  • Mercy Medical Center - Des Moines
  • McFarland Clinic - Trinity Cancer Center
  • McFarland Clinic - Jefferson
  • McFarland Clinic - Marshalltown
  • Tufts Medical Center
  • Saint Joseph Mercy Hospital
  • University of Michigan Comprehensive Cancer Center
  • Bronson Battle Creek
  • Saint Joseph Mercy Brighton
  • Trinity Health IHA Medical Group Hematology Oncology - Brighton
  • Saint Joseph Mercy Canton
  • Trinity Health IHA Medical Group Hematology Oncology - Canton
  • Saint Joseph Mercy Chelsea
  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
  • Wayne State University/Karmanos Cancer Institute
  • Weisberg Cancer Treatment Center
  • Genesee Cancer and Blood Disease Treatment Center
  • Genesee Hematology Oncology PC
  • Genesys Hurley Cancer Institute
  • Hurley Medical Center
  • Spectrum Health at Butterworth Campus
  • Trinity Health Grand Rapids Hospital
  • Bronson Methodist Hospital
  • West Michigan Cancer Center
  • Ascension Borgess Cancer Center
  • Sparrow Hospital
  • Trinity Health Saint Mary Mercy Livonia Hospital
  • Trinity Health Muskegon Hospital
  • Cancer and Hematology Centers of Western Michigan - Norton Shores
  • Spectrum Health Reed City Hospital
  • Marie Yeager Cancer Center
  • Munson Medical Center
  • University of Michigan Health - West
  • Huron Gastroenterology PC
  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
  • Essentia Health Saint Joseph's Medical Center
  • Mercy Hospital
  • Essentia Health - Deer River Clinic
  • Essentia Health Saint Mary's - Detroit Lakes Clinic
  • Essentia Health Cancer Center
  • Fairview Southdale Hospital
  • Essentia Health - Fosston
  • Unity Hospital
  • Essentia Health Hibbing Clinic
  • Essentia Health - Park Rapids
  • Mayo Clinic in Rochester
  • Park Nicollet Clinic - Saint Louis Park
  • Regions Hospital
  • United Hospital
  • Essentia Health Sandstone
  • Essentia Health Virginia Clinic
  • Minnesota Oncology Hematology PA-Woodbury
  • Saint Francis Medical Center
  • Community Hospital of Anaconda
  • Billings Clinic Cancer Center
  • Bozeman Deaconess Hospital
  • Benefis Healthcare- Sletten Cancer Institute
  • Kalispell Regional Medical Center
  • Community Medical Hospital
  • Nebraska Medicine-Bellevue
  • Nebraska Medicine-Village Pointe
  • University of Nebraska Medical Center
  • University of New Mexico Cancer Center
  • Northwell Health/Center for Advanced Medicine
  • Southeastern Medical Oncology Center-Clinton
  • Southeastern Medical Oncology Center-Goldsboro
  • Southeastern Medical Oncology Center-Jacksonville
  • Essentia Health Cancer Center-South University Clinic
  • Essentia Health - Jamestown Clinic
  • University of Oklahoma Health Sciences Center
  • Saint Charles Health System
  • Saint Alphonsus Medical Center-Ontario
  • Thomas Jefferson University Hospital
  • Jefferson Torresdale Hospital
  • Asplundh Cancer Pavilion
  • Huntsman Cancer Institute/University of Utah
  • Inova Schar Cancer Institute
  • Centra Lynchburg Hematology-Oncology Clinic Inc
  • Virginia Cancer Institute
  • VCU Massey Cancer Center at Stony Point
  • Virginia Commonwealth University/Massey Cancer Center
  • Duluth Clinic Ashland
  • Gundersen Lutheran Medical Center
  • ProHealth D N Greenwald Center
  • ProHealth Oconomowoc Memorial Hospital
  • ProHealth Waukesha Memorial Hospital
  • UW Cancer Center at ProHealth Care

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (nivolumab and cabozantinib)

Arm Description

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.

Outcomes

Primary Outcome Measures

Biomarker results turnaround time
A biomarker turnaround time estimate of at least 75% within 21 days will be considered successful with respect to feasibility.
Objective response rate
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.

Secondary Outcome Measures

Rate and profile of >= grade 3 treatment-related adverse events
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).
Disease control rate
Will be estimated using the method of Kaplan-Meier.
Progression-free survival
Will be estimated using the method of Kaplan-Meier.
Overall survival
Will be estimated using the method of Kaplan-Meier.
Turnaround time for the Tumor Inflammation Score in stage I

Full Information

First Posted
November 25, 2021
Last Updated
October 10, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05136196
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Suspended
Why Stopped
Scheduled Interim Monitoring
Study Start Date
December 6, 2022 (Actual)
Primary Completion Date
September 1, 2024 (Anticipated)
Study Completion Date
September 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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 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. VII. To assess turnaround time for TIS for at least 30 patients in stage I to ensure that at least 75% have a turnaround time of < 21 days. If TIS is not ready for real-time testing when 30 slots remain for Stage I, accrual will be paused until assay validation is complete. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Head and Neck Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma, Lip and Oral Cavity Squamous Cell Carcinoma, Melanoma, Oropharyngeal Squamous Cell Carcinoma, Stage III Hypopharyngeal Carcinoma AJCC v8, Stage III Laryngeal Cancer AJCC v8, Stage III Lip and Oral Cavity Cancer AJCC v8, Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8, Stage IV Hypopharyngeal Carcinoma AJCC v8, Stage IV Laryngeal Cancer AJCC v8, Stage IV Lip and Oral Cavity Cancer AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (nivolumab and cabozantinib)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
BIOPSY_TYPE, Bx
Intervention Description
Undergo tumor biopsies
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of blood samples
Intervention Type
Drug
Intervention Name(s)
Cabozantinib S-malate
Other Intervention Name(s)
BMS-907351, Cabometyx, Cometriq, XL-184, XL184
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo CT scans
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Intervention Description
Undergo MRI scans
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
ABP 206, BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Biomarker results turnaround time
Description
A biomarker turnaround time estimate of at least 75% within 21 days will be considered successful with respect to feasibility.
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
Title
Objective response rate
Description
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.
Time Frame
At the end of stage I
Secondary Outcome Measure Information:
Title
Rate and profile of >= grade 3 treatment-related adverse events
Description
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).
Time Frame
Up to 2 years
Title
Disease control rate
Description
Will be estimated using the method of Kaplan-Meier.
Time Frame
Up to 2 years
Title
Progression-free survival
Description
Will be estimated using the method of Kaplan-Meier.
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
Title
Overall survival
Description
Will be estimated using the method of Kaplan-Meier.
Time Frame
From date of registration to date of death due to any cause, assessed up to 2 years
Title
Turnaround time for the Tumor Inflammation Score in stage I
Time Frame
Assessed within 21 days
Other Pre-specified Outcome Measures:
Title
Additional markers of response or resistance
Description
Explore additional markers of response or resistance through hypothesis generating analysis.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 prior to progression. 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 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 surgery, chemotherapy, radiation therapy, biologic agents, or steroids within 14 days prior to step 1 registration Participants must not have received more than one prior primary radiotherapy regimen, curative or adjuvant, to 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) 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 not have active autoimmune disease requiring systemic steroids (equivalent of > 10mg of prednisone) or other immune suppression. Exceptions: Type 1 diabetes mellitus Hypothyroidism 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 known central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (e.g., carotid artery) 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 prior to step 1 registration as documented by 2 baseline blood pressure readings taken at least 30 minutes apart within 28 days prior to step 1 registration. The baseline systolic blood pressure readings must be =< 150 mmHg and the baseline diastolic blood pressure readings must be =< 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 adequate tissue specimen from procedure obtained within 6 months prior to step 1 registration and after development of resistance to anti-PD-1/L1 therapy. Archival tissue must consist of tumor block or at least 20 freshly cut serially sectioned and numbered 4-5 micron unstained, positively-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 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 Participants must have been eligible for step 1 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 more than one prior primary radiotherapy regimen, curative or adjuvant, to the head and neck, with the additional following conditions: 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 2 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 2 registration Additional palliative radiotherapy regimens are permitted but cannot have been administered to previously treated tissue (i.e., overlapping fields are excluded) and must be completed at least 4 weeks prior to step 2 registration Treatment areas should be healed with no sequelae from RT that would predispose to fistula formation 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 any prior treatment with anti-VEGF based therapies 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 Participants must be able to take oral medication without breaking, opening, crushing, dissolving or chewing capsules 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 Participants must not have malabsorption syndrome Participants must not have central lung lesions involving major blood vessels (arteries or veins) or a tumor encasing major blood vessels (e.g., carotid artery)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Siwen Hu-Lieskovan
Organizational Affiliation
SWOG Cancer Research Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Rocky Mountain Regional VA Medical Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
UCHealth Memorial Hospital Central
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80909
Country
United States
Facility Name
Memorial Hospital North
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80920
Country
United States
Facility Name
Poudre Valley Hospital
City
Fort Collins
State/Province
Colorado
ZIP/Postal Code
80524
Country
United States
Facility Name
Cancer Care and Hematology-Fort Collins
City
Fort Collins
State/Province
Colorado
ZIP/Postal Code
80528
Country
United States
Facility Name
UCHealth Greeley Hospital
City
Greeley
State/Province
Colorado
ZIP/Postal Code
80631
Country
United States
Facility Name
Medical Center of the Rockies
City
Loveland
State/Province
Colorado
ZIP/Postal Code
80538
Country
United States
Facility Name
Helen F Graham Cancer Center
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Medical Oncology Hematology Consultants PA
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Facility Name
Saint Alphonsus Cancer Care Center-Boise
City
Boise
State/Province
Idaho
ZIP/Postal Code
83706
Country
United States
Facility Name
Saint Luke's Cancer Institute - Boise
City
Boise
State/Province
Idaho
ZIP/Postal Code
83712
Country
United States
Facility Name
Saint Alphonsus Cancer Care Center-Caldwell
City
Caldwell
State/Province
Idaho
ZIP/Postal Code
83605
Country
United States
Facility Name
Kootenai Health - Coeur d'Alene
City
Coeur d'Alene
State/Province
Idaho
ZIP/Postal Code
83814
Country
United States
Facility Name
Saint Luke's Cancer Institute - Fruitland
City
Fruitland
State/Province
Idaho
ZIP/Postal Code
83619
Country
United States
Facility Name
Saint Luke's Cancer Institute - Meridian
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
Saint Luke's Cancer Institute - Nampa
City
Nampa
State/Province
Idaho
ZIP/Postal Code
83686
Country
United States
Facility Name
Saint Alphonsus Cancer Care Center-Nampa
City
Nampa
State/Province
Idaho
ZIP/Postal Code
83687
Country
United States
Facility Name
Kootenai Clinic Cancer Services - Post Falls
City
Post Falls
State/Province
Idaho
ZIP/Postal Code
83854
Country
United States
Facility Name
Kootenai Cancer Clinic
City
Sandpoint
State/Province
Idaho
ZIP/Postal Code
83864
Country
United States
Facility Name
Saint Luke's Cancer Institute - Twin Falls
City
Twin Falls
State/Province
Idaho
ZIP/Postal Code
83301
Country
United States
Facility Name
Rush - Copley Medical Center
City
Aurora
State/Province
Illinois
ZIP/Postal Code
60504
Country
United States
Facility Name
Illinois CancerCare-Bloomington
City
Bloomington
State/Province
Illinois
ZIP/Postal Code
61704
Country
United States
Facility Name
Illinois CancerCare-Canton
City
Canton
State/Province
Illinois
ZIP/Postal Code
61520
Country
United States
Facility Name
Illinois CancerCare-Carthage
City
Carthage
State/Province
Illinois
ZIP/Postal Code
62321
Country
United States
Facility Name
Centralia Oncology Clinic
City
Centralia
State/Province
Illinois
ZIP/Postal Code
62801
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Carle at The Riverfront
City
Danville
State/Province
Illinois
ZIP/Postal Code
61832
Country
United States
Facility Name
Cancer Care Specialists of Illinois - Decatur
City
Decatur
State/Province
Illinois
ZIP/Postal Code
62526
Country
United States
Facility Name
Decatur Memorial Hospital
City
Decatur
State/Province
Illinois
ZIP/Postal Code
62526
Country
United States
Facility Name
Northwestern Medicine Cancer Center Kishwaukee
City
DeKalb
State/Province
Illinois
ZIP/Postal Code
60115
Country
United States
Facility Name
Illinois CancerCare-Dixon
City
Dixon
State/Province
Illinois
ZIP/Postal Code
61021
Country
United States
Facility Name
Carle Physician Group-Effingham
City
Effingham
State/Province
Illinois
ZIP/Postal Code
62401
Country
United States
Facility Name
Crossroads Cancer Center
City
Effingham
State/Province
Illinois
ZIP/Postal Code
62401
Country
United States
Facility Name
Illinois CancerCare-Eureka
City
Eureka
State/Province
Illinois
ZIP/Postal Code
61530
Country
United States
Facility Name
Illinois CancerCare-Galesburg
City
Galesburg
State/Province
Illinois
ZIP/Postal Code
61401
Country
United States
Facility Name
Northwestern Medicine Cancer Center Delnor
City
Geneva
State/Province
Illinois
ZIP/Postal Code
60134
Country
United States
Facility Name
Illinois CancerCare-Kewanee Clinic
City
Kewanee
State/Province
Illinois
ZIP/Postal Code
61443
Country
United States
Facility Name
Northwestern Medicine Lake Forest Hospital
City
Lake Forest
State/Province
Illinois
ZIP/Postal Code
60045
Country
United States
Facility Name
Illinois CancerCare-Macomb
City
Macomb
State/Province
Illinois
ZIP/Postal Code
61455
Country
United States
Facility Name
Carle Physician Group-Mattoon/Charleston
City
Mattoon
State/Province
Illinois
ZIP/Postal Code
61938
Country
United States
Facility Name
Cancer Care Center of O'Fallon
City
O'Fallon
State/Province
Illinois
ZIP/Postal Code
62269
Country
United States
Facility Name
Illinois CancerCare-Ottawa Clinic
City
Ottawa
State/Province
Illinois
ZIP/Postal Code
61350
Country
United States
Facility Name
Illinois CancerCare-Pekin
City
Pekin
State/Province
Illinois
ZIP/Postal Code
61554
Country
United States
Facility Name
Illinois CancerCare-Peoria
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Facility Name
Illinois CancerCare-Peru
City
Peru
State/Province
Illinois
ZIP/Postal Code
61354
Country
United States
Facility Name
Illinois CancerCare-Princeton
City
Princeton
State/Province
Illinois
ZIP/Postal Code
61356
Country
United States
Facility Name
Southern Illinois University School of Medicine
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
Springfield Clinic
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
Memorial Medical Center
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62781
Country
United States
Facility Name
Carle Cancer Center
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Northwestern Medicine Cancer Center Warrenville
City
Warrenville
State/Province
Illinois
ZIP/Postal Code
60555
Country
United States
Facility Name
Illinois CancerCare - Washington
City
Washington
State/Province
Illinois
ZIP/Postal Code
61571
Country
United States
Facility Name
Rush-Copley Healthcare Center
City
Yorkville
State/Province
Illinois
ZIP/Postal Code
60560
Country
United States
Facility Name
Mary Greeley Medical Center
City
Ames
State/Province
Iowa
ZIP/Postal Code
50010
Country
United States
Facility Name
McFarland Clinic - Ames
City
Ames
State/Province
Iowa
ZIP/Postal Code
50010
Country
United States
Facility Name
McFarland Clinic - Boone
City
Boone
State/Province
Iowa
ZIP/Postal Code
50036
Country
United States
Facility Name
Mercy Hospital
City
Cedar Rapids
State/Province
Iowa
ZIP/Postal Code
52403
Country
United States
Facility Name
Oncology Associates at Mercy Medical Center
City
Cedar Rapids
State/Province
Iowa
ZIP/Postal Code
52403
Country
United States
Facility Name
Medical Oncology and Hematology Associates-Des Moines
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50309
Country
United States
Facility Name
Mercy Medical Center - Des Moines
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50314
Country
United States
Facility Name
McFarland Clinic - Trinity Cancer Center
City
Fort Dodge
State/Province
Iowa
ZIP/Postal Code
50501
Country
United States
Facility Name
McFarland Clinic - Jefferson
City
Jefferson
State/Province
Iowa
ZIP/Postal Code
50129
Country
United States
Facility Name
McFarland Clinic - Marshalltown
City
Marshalltown
State/Province
Iowa
ZIP/Postal Code
50158
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Saint Joseph Mercy Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Bronson Battle Creek
City
Battle Creek
State/Province
Michigan
ZIP/Postal Code
49017
Country
United States
Facility Name
Saint Joseph Mercy Brighton
City
Brighton
State/Province
Michigan
ZIP/Postal Code
48114
Country
United States
Facility Name
Trinity Health IHA Medical Group Hematology Oncology - Brighton
City
Brighton
State/Province
Michigan
ZIP/Postal Code
48114
Country
United States
Facility Name
Saint Joseph Mercy Canton
City
Canton
State/Province
Michigan
ZIP/Postal Code
48188
Country
United States
Facility Name
Trinity Health IHA Medical Group Hematology Oncology - Canton
City
Canton
State/Province
Michigan
ZIP/Postal Code
48188
Country
United States
Facility Name
Saint Joseph Mercy Chelsea
City
Chelsea
State/Province
Michigan
ZIP/Postal Code
48118
Country
United States
Facility Name
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
City
Chelsea
State/Province
Michigan
ZIP/Postal Code
48118
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Weisberg Cancer Treatment Center
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
Genesee Cancer and Blood Disease Treatment Center
City
Flint
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Facility Name
Genesee Hematology Oncology PC
City
Flint
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Facility Name
Genesys Hurley Cancer Institute
City
Flint
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Facility Name
Hurley Medical Center
City
Flint
State/Province
Michigan
ZIP/Postal Code
48503
Country
United States
Facility Name
Spectrum Health at Butterworth Campus
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Trinity Health Grand Rapids Hospital
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Bronson Methodist Hospital
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
West Michigan Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
Ascension Borgess Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49009
Country
United States
Facility Name
Sparrow Hospital
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48912
Country
United States
Facility Name
Trinity Health Saint Mary Mercy Livonia Hospital
City
Livonia
State/Province
Michigan
ZIP/Postal Code
48154
Country
United States
Facility Name
Trinity Health Muskegon Hospital
City
Muskegon
State/Province
Michigan
ZIP/Postal Code
49444
Country
United States
Facility Name
Cancer and Hematology Centers of Western Michigan - Norton Shores
City
Norton Shores
State/Province
Michigan
ZIP/Postal Code
49444
Country
United States
Facility Name
Spectrum Health Reed City Hospital
City
Reed City
State/Province
Michigan
ZIP/Postal Code
49677
Country
United States
Facility Name
Marie Yeager Cancer Center
City
Saint Joseph
State/Province
Michigan
ZIP/Postal Code
49085
Country
United States
Facility Name
Munson Medical Center
City
Traverse City
State/Province
Michigan
ZIP/Postal Code
49684
Country
United States
Facility Name
University of Michigan Health - West
City
Wyoming
State/Province
Michigan
ZIP/Postal Code
49519
Country
United States
Facility Name
Huron Gastroenterology PC
City
Ypsilanti
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
City
Ypsilanti
State/Province
Michigan
ZIP/Postal Code
48197
Country
United States
Facility Name
Essentia Health Saint Joseph's Medical Center
City
Brainerd
State/Province
Minnesota
ZIP/Postal Code
56401
Country
United States
Facility Name
Mercy Hospital
City
Coon Rapids
State/Province
Minnesota
ZIP/Postal Code
55433
Country
United States
Facility Name
Essentia Health - Deer River Clinic
City
Deer River
State/Province
Minnesota
ZIP/Postal Code
56636
Country
United States
Facility Name
Essentia Health Saint Mary's - Detroit Lakes Clinic
City
Detroit Lakes
State/Province
Minnesota
ZIP/Postal Code
56501
Country
United States
Facility Name
Essentia Health Cancer Center
City
Duluth
State/Province
Minnesota
ZIP/Postal Code
55805
Country
United States
Facility Name
Fairview Southdale Hospital
City
Edina
State/Province
Minnesota
ZIP/Postal Code
55435
Country
United States
Facility Name
Essentia Health - Fosston
City
Fosston
State/Province
Minnesota
ZIP/Postal Code
56542
Country
United States
Facility Name
Unity Hospital
City
Fridley
State/Province
Minnesota
ZIP/Postal Code
55432
Country
United States
Facility Name
Essentia Health Hibbing Clinic
City
Hibbing
State/Province
Minnesota
ZIP/Postal Code
55746
Country
United States
Facility Name
Essentia Health - Park Rapids
City
Park Rapids
State/Province
Minnesota
ZIP/Postal Code
56470
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Park Nicollet Clinic - Saint Louis Park
City
Saint Louis Park
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
Regions Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55101
Country
United States
Facility Name
United Hospital
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55102
Country
United States
Facility Name
Essentia Health Sandstone
City
Sandstone
State/Province
Minnesota
ZIP/Postal Code
55072
Country
United States
Facility Name
Essentia Health Virginia Clinic
City
Virginia
State/Province
Minnesota
ZIP/Postal Code
55792
Country
United States
Facility Name
Minnesota Oncology Hematology PA-Woodbury
City
Woodbury
State/Province
Minnesota
ZIP/Postal Code
55125
Country
United States
Facility Name
Saint Francis Medical Center
City
Cape Girardeau
State/Province
Missouri
ZIP/Postal Code
63703
Country
United States
Facility Name
Community Hospital of Anaconda
City
Anaconda
State/Province
Montana
ZIP/Postal Code
59711
Country
United States
Facility Name
Billings Clinic Cancer Center
City
Billings
State/Province
Montana
ZIP/Postal Code
59101
Country
United States
Facility Name
Bozeman Deaconess Hospital
City
Bozeman
State/Province
Montana
ZIP/Postal Code
59715
Country
United States
Facility Name
Benefis Healthcare- Sletten Cancer Institute
City
Great Falls
State/Province
Montana
ZIP/Postal Code
59405
Country
United States
Facility Name
Kalispell Regional Medical Center
City
Kalispell
State/Province
Montana
ZIP/Postal Code
59901
Country
United States
Facility Name
Community Medical Hospital
City
Missoula
State/Province
Montana
ZIP/Postal Code
59804
Country
United States
Facility Name
Nebraska Medicine-Bellevue
City
Bellevue
State/Province
Nebraska
ZIP/Postal Code
68123
Country
United States
Facility Name
Nebraska Medicine-Village Pointe
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68118
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
Northwell Health/Center for Advanced Medicine
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Southeastern Medical Oncology Center-Clinton
City
Clinton
State/Province
North Carolina
ZIP/Postal Code
28328
Country
United States
Facility Name
Southeastern Medical Oncology Center-Goldsboro
City
Goldsboro
State/Province
North Carolina
ZIP/Postal Code
27534
Country
United States
Facility Name
Southeastern Medical Oncology Center-Jacksonville
City
Jacksonville
State/Province
North Carolina
ZIP/Postal Code
28546
Country
United States
Facility Name
Essentia Health Cancer Center-South University Clinic
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58103
Country
United States
Facility Name
Essentia Health - Jamestown Clinic
City
Jamestown
State/Province
North Dakota
ZIP/Postal Code
58401
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Saint Charles Health System
City
Bend
State/Province
Oregon
ZIP/Postal Code
97701
Country
United States
Facility Name
Saint Alphonsus Medical Center-Ontario
City
Ontario
State/Province
Oregon
ZIP/Postal Code
97914
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Jefferson Torresdale Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19114
Country
United States
Facility Name
Asplundh Cancer Pavilion
City
Willow Grove
State/Province
Pennsylvania
ZIP/Postal Code
19090
Country
United States
Facility Name
Huntsman Cancer Institute/University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Inova Schar Cancer Institute
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Centra Lynchburg Hematology-Oncology Clinic Inc
City
Lynchburg
State/Province
Virginia
ZIP/Postal Code
24501
Country
United States
Facility Name
Virginia Cancer Institute
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23229
Country
United States
Facility Name
VCU Massey Cancer Center at Stony Point
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23235
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Duluth Clinic Ashland
City
Ashland
State/Province
Wisconsin
ZIP/Postal Code
54806
Country
United States
Facility Name
Gundersen Lutheran Medical Center
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
ProHealth D N Greenwald Center
City
Mukwonago
State/Province
Wisconsin
ZIP/Postal Code
53149
Country
United States
Facility Name
ProHealth Oconomowoc Memorial Hospital
City
Oconomowoc
State/Province
Wisconsin
ZIP/Postal Code
53066
Country
United States
Facility Name
ProHealth Waukesha Memorial Hospital
City
Waukesha
State/Province
Wisconsin
ZIP/Postal Code
53188
Country
United States
Facility Name
UW Cancer Center at ProHealth Care
City
Waukesha
State/Province
Wisconsin
ZIP/Postal Code
53188
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
IPD Sharing URL
https://grants.nih.gov/policy/sharing.htm

Learn more about this trial

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

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