Testing Cabozantinib With or Without Atezolizumab in Patients With Advanced Papillary Kidney Cancer, PAPMET2 Trial

A Phase II Randomized Trial of Cabozantinib (NSC #761968) With or Without Atezolizumab (NSC #783608) in Patients With Advanced Papillary Renal Cell Carcinoma (PAPMET2)

This phase II trial compares the effect of atezolizumab in combination with usual treatment with cabozantinib to cabozantinib alone in patients with papillary renal cell carcinoma that has spread from where it first started (primary site) to other places in the body (metastatic). Papillary renal cell carcinoma (PRCC) is a type of kidney cancer that forms in the lining of the tiny tubes in the kidney that return filtered substances that the body needs back to the blood and remove extra fluid and waste as urine. Most papillary tumors look like long, thin finger-like growths under a microscope. It is also called papillary kidney cancer or PRCC. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply and may also prevent the growth of new blood vessels that tumors need to grow. By these actions it may help slow or stop the spread of tumor cells. Combination therapy with atezolizumab and cabozantinib may shrink the tumor and allow a longer survival time in patients with metastatic renal cell carcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Stage IV Renal Cell Cancer AJCC v8; Metastatic Papillary Renal Cell Carcinoma
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Drug: Cabozantinib S-malate; Biological: Atezolizumab; Procedure: Computed Tomography; Procedure: Bone Scan; Procedure: Biospecimen Collection

Detailed Description

PRIMARY OBJECTIVE:

I. To compare progression-free survival in participants with metastatic papillary renal cell carcinoma (mPRCC) randomized to cabozantinib (cabozantinib S-malate) with atezolizumab versus cabozantinib alone.

SECONDARY OBJECTIVES:

I. To compare overall survival in participants with mPRCC randomized to cabozantinib with atezolizumab versus cabozantinib alone.

II. To compare Response Evaluation Criteria in Solid Tumors (RECIST) objective response rate (confirmed and unconfirmed, complete and partial response) in participants with mPRCC randomized to cabozantinib with atezolizumab versus cabozantinib alone.

III. To evaluate the quantitative and qualitive adverse events observed in each treatment arm.

BANKING OBJECTIVE:

I. To bank biospecimens for future correlative studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive cabozantinib S-malate orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood and urine sample collection throughout the trial. Patients may also undergo bone scan throughout the trial.

ARM II: Patients receive cabozantinib S-malate PO QD on days 1-21 and atezolizumab intravenously (IV) over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI and blood and urine sample collection throughout the trial. Patients may also undergo bone scan throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for up to 5 years.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85004
      • Cancer Center at Saint Joseph's
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Anaheim, California, United States, 92806
      • Kaiser Permanente-Anaheim
    • Baldwin Park, California, United States, 91706
      • Kaiser Permanente-Baldwin Park
    • Bellflower, California, United States, 90706
      • Kaiser Permanente-Bellflower
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Dublin, California, United States, 94568
      • Epic Care-Dublin
    • Emeryville, California, United States, 94608
      • Epic Care Partners in Cancer Care
    • Fontana, California, United States, 92335
      • Kaiser Permanente-Fontana
    • Harbor City, California, United States, 90710
      • Kaiser Permanente South Bay
    • Irvine, California, United States, 92618
      • Kaiser Permanente-Irvine
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90034
      • Kaiser Permanente West Los Angeles
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Ontario, California, United States, 91761
      • Kaiser Permanente-Ontario
    • Panorama City, California, United States, 91402
      • Kaiser Permanente - Panorama City
    • Riverside, California, United States, 92505
      • Kaiser Permanente-Riverside
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • San Diego, California, United States, 92120
      • Kaiser Permanente-San Diego Zion
    • San Marcos, California, United States, 92078
      • Kaiser Permanente-San Marcos
    • Walnut Creek, California, United States, 94597
      • Epic Care Cyberknife Center
    • Woodland Hills, California, United States, 91367
      • Kaiser Permanente-Woodland Hills
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Health - Coeur d'Alene
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83687
      • Saint Alphonsus Cancer Care Center-Nampa
    • Nampa, Idaho, United States, 83687
      • Saint Luke's Cancer Institute - Nampa
    • Post Falls, Idaho, United States, 83854
      • Kootenai Clinic Cancer Services - Post Falls
    • Sandpoint, Idaho, United States, 83864
      • Kootenai Clinic Cancer Services - Sandpoint
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Cancer Institute - Twin Falls
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • DeKalb, Illinois, United States, 60115
      • Northwestern Medicine Cancer Center Kishwaukee
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Dixon, Illinois, United States, 61021
      • Illinois CancerCare-Dixon
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Geneva, Illinois, United States, 60134
      • Northwestern Medicine Cancer Center Delnor
    • Glenview, Illinois, United States, 60026
      • Northwestern Medicine Glenview Outpatient Center
    • Grayslake, Illinois, United States, 60030
      • Northwestern Medicine Grayslake Outpatient Center
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Lake Forest, Illinois, United States, 60045
      • Northwestern Medicine Lake Forest Hospital
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • O'Fallon, Illinois, United States, 62269
      • Cancer Care Center of O'Fallon
    • Orland Park, Illinois, United States, 60462
      • Northwestern Medicine Orland Park
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Rockford, Illinois, United States, 61114
      • UW Health Carbone Cancer Center Rockford
    • Shiloh, Illinois, United States, 62269
      • Memorial Hospital East
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Springfield, Illinois, United States, 62781
      • Springfield Memorial Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Warrenville, Illinois, United States, 60555
      • Northwestern Medicine Cancer Center Warrenville
    • Washington, Illinois, United States, 61571
      • Illinois CancerCare - Washington
  • Iowa
    • Ames, Iowa, United States, 50010
      • Mary Greeley Medical Center
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Ankeny, Iowa, United States, 50023
      • UI Health Care Mission Cancer and Blood - Ankeny Clinic
    • Boone, Iowa, United States, 50036
      • McFarland Clinic - Boone
    • Clive, Iowa, United States, 50325
      • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • UI Health Care Mission Cancer and Blood - Des Moines Clinic
    • Des Moines, Iowa, United States, 50314
      • UI Health Care Mission Cancer and Blood - Laurel Clinic
    • Fort Dodge, Iowa, United States, 50501
      • McFarland Clinic - Trinity Cancer Center
    • Jefferson, Iowa, United States, 50129
      • McFarland Clinic - Jefferson
    • Marshalltown, Iowa, United States, 50158
      • McFarland Clinic - Marshalltown
    • Waukee, Iowa, United States, 50263
      • UI Health Care Mission Cancer and Blood - Waukee Clinic
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Cancer Center / Stormont Vail Health
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • East Jefferson General Hospital
    • Metairie, Louisiana, United States, 70006
      • LSU Healthcare Network / Metairie Multi-Specialty Clinic
    • Metairie, Louisiana, United States, 70002
      • Mary Bird Perkins Cancer Center - Metairie
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
    • New Orleans, Louisiana, United States, 70115
      • Touro Infirmary
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Brighton, Michigan, United States, 48114
      • Trinity Health IHA Medical Group Hematology Oncology - Brighton
    • Brighton, Michigan, United States, 48114
      • Trinity Health Medical Center - Brighton
    • Canton, Michigan, United States, 48188
      • Trinity Health IHA Medical Group Hematology Oncology - Canton
    • Canton, Michigan, United States, 48188
      • Trinity Health Medical Center - Canton
    • Caro, Michigan, United States, 48723
      • Caro Cancer Center
    • Chelsea, Michigan, United States, 48118
      • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
    • Chelsea, Michigan, United States, 48118
      • Chelsea Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Farmington Hills, Michigan, United States, 48334
      • Weisberg Cancer Treatment Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesee Hematology Oncology PC
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Flint, Michigan, United States, 48503
      • Cancer Hematology Centers - Flint
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49009
      • Beacon Kalamazoo Cancer Center
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Marlette, Michigan, United States, 48453
      • Saint Mary's Oncology/Hematology Associates of Marlette
    • Muskegon, Michigan, United States, 49444
      • Trinity Health Muskegon Hospital
    • Niles, Michigan, United States, 49120
      • Corewell Health Lakeland Hospitals - Niles Hospital
    • Norton Shores, Michigan, United States, 49444
      • Cancer and Hematology Centers of Western Michigan - Norton Shores
    • Pontiac, Michigan, United States, 48341
      • Trinity Health Saint Joseph Mercy Oakland Hospital
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Saginaw, Michigan, United States, 48601
      • MyMichigan Medical Center Saginaw
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
    • Tawas City, Michigan, United States, 48764
      • MyMichigan Medical Center Tawas
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Wyoming, Michigan, United States, 49519
      • University of Michigan Health - West
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Ypsilanti, Michigan, United States, 48106
      • Huron Gastroenterology PC
  • Minnesota
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • City of Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Farmington, Missouri, United States, 63640
      • Parkland Health Center - Farmington
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • St Louis, Missouri, United States, 63136
      • Siteman Cancer Center at Christian Hospital
    • St Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • St Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • St Louis, Missouri, United States, 63128
      • Mercy Hospital South
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • BJC Outpatient Center at Sunset Hills
  • Montana
    • Anaconda, Montana, United States, 59711
      • Community Hospital of Anaconda
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59102
      • Saint Vincent Frontier Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Health Deaconess Hospital
    • Great Falls, Montana, United States, 59405
      • Benefis Sletten Cancer Institute
    • Kalispell, Montana, United States, 59901
      • Logan Health Medical Center
    • Missoula, Montana, United States, 59804
      • Community Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • OptumCare Cancer Care at Charleston
    • Las Vegas, Nevada, United States, 89183
      • OptumCare Cancer Care at Fort Apache
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Duke Cancer Center Cary
    • Clinton, North Carolina, United States, 28328
      • Southeastern Medical Oncology Center-Clinton
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Southeastern Medical Oncology Center-Goldsboro
    • Jacksonville, North Carolina, United States, 28546
      • Southeastern Medical Oncology Center-Jacksonville
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
    • Raleigh, North Carolina, United States, 27609
      • Duke Cancer Center Raleigh
  • Ohio
    • Avon, Ohio, United States, 44011
      • UH Seidman Cancer Center at UH Avon Health Center
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Dayton, Ohio, United States, 45415
      • Dayton Physician LLC - Englewood
    • Dayton, Ohio, United States, 45409
      • Premier Blood and Cancer Center
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Miami Valley Cancer Care and Infusion
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Oregon
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Ontario, Oregon, United States, 97914
      • Saint Alphonsus Cancer Care Center-Ontario
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Dallas, Texas, United States, 75237
      • UT Southwestern Simmons Cancer Center - RedBird
    • Fort Worth, Texas, United States, 76104
      • UT Southwestern/Simmons Cancer Center-Fort Worth
    • Richardson, Texas, United States, 75080
      • UT Southwestern Clinical Center at Richardson/Plano
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Farmington, Utah, United States, 84025
      • Farmington Health Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23235
      • VCU Massey Cancer Center at Stony Point
    • Richmond, Virginia, United States, 23298
      • VCU Massey Comprehensive Cancer Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston Division
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Medical Center-EC Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Medical Center - Minocqua
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Medical Center-Rice Lake
    • Stevens Point, Wisconsin, United States, 54482
      • Marshfield Medical Center-River Region at Stevens Point
    • Weston, Wisconsin, United States, 54476
      • Marshfield Medical Center - Weston

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must have a histologically confirmed diagnosis of metastatic papillary renal cell carcinoma (PRCC), either type 1 or type 2. (NOTE: A designation of type 1 or type 2 should be made by the local pathologist if possible but is not required). Mixed histologies which contain type 1 or type 2 along with any other RCC histology/histologies will be allowed provided that they contain a papillary component
• Participants must have measurable disease per RECIST 1.1 criteria. All measurable lesions must be assessed by CT or MRI within 28 days prior to registration. All non-measurable lesions must be assessed by CT or MRI, or nuclear medicine bone scan within 42 days prior to registration. The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. If there is clinical suspicion for bone metastases at the time of enrollment (at the discretion of the investigator), bone scan must be performed at baseline (within 42 days prior to registration)
• Participants with new or progressive brain metastases (active brain metastases) must not require immediate central nervous system (CNS) specific treatment at the time of study registration or anticipated during the first cycle of therapy. Patients with leptomeningeal disease are excluded from enrolling
• Participants with measurable disease, per RECIST version (v)1.1, must be present outside the CNS
• Participants must have no history of intracranial hemorrhage or spinal cord hemorrhage
• Participants must not have undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment
• Participants must not have ongoing requirements for corticosteroids as therapy for CNS disease
• Participants, if needed, must receive a stable dose of anti-convulsant therapy
• Participants must not have cavitating pulmonary lesions
• Participants must not have uncontrolled pleural effusions, pericardial effusions, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters (e.g., PleurX [registered trademark]) are allowed
• Participants must not have tumor invading the gastrointestinal (GI) tract or evidence of endotracheal or endobronchial tumor within 28 days prior to registration
• Participants must not have evidence of tumor invading or encasing any major blood vessels
• Participants must not have had major surgery within 28 days prior to registration, and participants must have recovered from any adverse effects of surgery
• Participants must not have had prior treatment with cabozantinib for any reason
• Participants must not have had prior treatment or adjuvant therapy with PD-1/PD-L1 checkpoint inhibitors for any reason within the past 6 months
• Participants must not have received more than one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib). If a participant develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic RCC. If a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC
• Participants must not take within 14 days prior to registration, nor plan to take while on protocol treatment, any strong CYP3A4 inhibitors (e.g. boceprevir, cobicistat, danoprevir, elvitegravir/RIT, fluvoxamine, indinavir, itraconazole, ketoconazole, lopinavir/RIT, nefazodone, nelfinavir, posaconazole, ritonavir, telaprevir, telithromycin, tipranavir/RIT, or voriconazole,); Please refer to https://drug-interactions.medicine.iu.edu/MainTable.aspx for the updated CYP3A4 inhibitors or inducers
• Participants must not take within 14 days prior to registration, nor plan to take while on protocol treatment, any strong CYP3A4 inducers (e.g. avasimibe, phenytoin, rifampin, rifabutin); Please refer to https://drug-interactions.medicine.iu.edu/MainTable.aspx for the updated CYP3A4 inhibitors or inducers
• Participants must complete all prior radiation therapy at least 14 days prior to registration. Participants must have recovered to =< grade 1 from all associated toxicities at the time of registration unless the toxicity is determined to be not clinically significant by the registering investigator
• Participants must not be receiving or planning to receive any other investigational agents at time of registration
• Participants must not have been diagnosed with a clinically significant autoimmune disease, exceptions such as diabetes, eczema, and vitiligo are allowed. Other non-clinically significant autoimmune diseases are allowed if approved by the registering investigator
• Participants must not be on steroid doses > 10 mg prednisone equivalent. Replacement steroid doses for adrenal insufficiency will be allowed. Also, short duration steroid therapy to prevent allergic reactions are acceptable (e.g. prior to CT imaging)
• Participants must be >= 18 years of age
• Participants must have a complete physical examination and medical history within 28 days prior to registration
• Participants must have a Zubrod performance status of 0-2
• White blood count (WBC) >= 2 x 10^3/uL (within 28 days prior to registration)
• Absolute neutrophil count (ANC) >= 1.5 x 10^3/uL (within 28 days prior to registration)
• Platelet count >= 100 x 10^3/uL (within 28 days prior to registration)
• Lymphocyte count >= 0.5 x 10^3/uL (within 28 days prior to registration)
• Hemoglobin (>= 9 g/dL) (within 28 days prior to registration). Participants may be transfused to meet this criterion
• Total serum bilirubin =< 1.5 x the institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to registration). Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN
• Aspartate aminotransferase (AST) must be =< 3 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT) must be =< 5 x the institutional ULN (within 28 days prior to registration)
• Alanine aminotransferase (ALT), must be =< 3 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGPT) must be =< 5 x the institutional ULN (within 28 days prior to registration)
• Participants must have serum creatinine =< 2 x the institutional ULN OR creatinine clearance (either measured or calculated) > 30 mL/min and obtained within 28 days prior to registration
• Participants must not have any clinical evidence of congestive heart failure (CHF) (specifically, New York Heart Association [NYHA] class III [moderate] or class IV [severe]) at the time of registration
• 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 registration
• Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days of registration, unless clinically stable with ongoing medical management
• Participants must have urine protein < 3+ within 28 days prior to registration. If urine protein is 3+ or greater, then urine protein by 24-hour collection must show less than 3 grams of protein
• Participants must have documented blood pressure of systolic blood pressure (SBP) < 150 mm Hg or diastolic blood pressure (DBP) < 100 mm Hg within 14 days prior to registration
• Participants with known human immunodeficiency virus (HIV) must be on effective anti-retroviral therapy at registration and have undetectable viral load within 6 months of registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy within 6 months prior to registration, if indicated
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load within 6 months prior to registration
• Participants must be able to take oral medications (i.e., swallow pills whole). Participants must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures that could in the opinion of the treating investigator affect absorption, or active peptic ulcer disease. Participants with intractable nausea or vomiting are not eligible
• Participants must not have had any clinically-significant GI bleeding within 3 months prior to registration and participants must not have a GI disorder which (at the discretion of the investigator) bears a high risk of perforation or fistula (e.g. Crohn's disease)
• Participants must not have had hemoptysis of >= (2.5 mL) of red blood, and do not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior registration
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Participants must not be pregnant or nursing, due to VEGF therapy being toxic to embryogenesis. 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
• Participants must not be on warfarin, at therapeutic doses. Low dose aspirin for cardio-protection (per local applicable guidelines) and low molecular weight heparin (LMWH) are allowed
• Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking 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

  • NOTE: For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
• As a part of the 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (cabozantinib S-malate); Patients receive cabozantinib S-malate PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI and blood and urine sample collection throughout the trial. Patients may also undergo bone scan throughout the trial.	Procedure: Magnetic Resonance Imaging; Undergo MRI; 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; Drug: Cabozantinib S-malate; Given PO; Other Names: BMS-907351; Cabometyx; Cometriq; XL-184; XL184; XL 184; 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; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Bone Scan; Undergo bone scans; Other Names: Bone Scintigraphy; Procedure: Biospecimen Collection; Undergo collection of blood and urine samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection
Experimental: Arm II (cabozantinib S-malate, atezolizumab); Patients receive cabozantinib S-malate PO QD on days 1-21 and atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan or MRI and blood and urine sample collection throughout the trial. Patients may also undergo bone scan throughout the trial.	Procedure: Magnetic Resonance Imaging; Undergo MRI; 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; Drug: Cabozantinib S-malate; Given PO; Other Names: BMS-907351; Cabometyx; Cometriq; XL-184; XL184; XL 184; Biological: Atezolizumab; Given IV; Other Names: Tecentriq; MPDL3280A; RO5541267; RG7446; MPDL 3280A; MPDL 328OA; MPDL-3280A; MPDL328OA; RG-7446; RG 7446; RO 5541267; RO-5541267; 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; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Bone Scan; Undergo bone scans; Other Names: Bone Scintigraphy; Procedure: Biospecimen Collection; Undergo collection of blood and urine samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	A proportional hazards model will be used to evaluate the experimental arm compared to the control arm, adjusted for the stratification factors as covariates in the model. A one-sided p-value =< 0.05 will indicate statistical significance. Participants last known to be alive and progression free are censored at date of last contact.	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Will be estimated by the Kaplan-Meier method, and a stratified log-rank test will be used to compare the treatment arms. Participants last known to be alive are censored at date of last contact.	From date of registration to date of death due to any cause, assessed up to 5 years
Objective response rate	Will be estimated to within +/- 11% (95% confidence interval).	Up to 5 years
Incidence of adverse events	Will be estimated to within +/- 11% (95% confidence interval). Will utilize the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 for toxicity and serious adverse event reporting.	Day 1 of each cycle

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Benjamin L Maughan, SWOG Cancer Research Network

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Spectrum Analysis; Specimen Handling; Magnetic Resonance Spectroscopy; atezolizumab; cabozantinib
• Other Study ID Numbers: NCI-2022-04668 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180888 (U.S. NIH Grant/Contract); S2200 (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
• product manufactured in and exported from the U.S.: No