Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy

Metastatic Renal Cell Carcinoma Clinical Trial

— PROSPER  

Official title:

A Phase 3 RandOmized Study Comparing PERioperative Nivolumab vs. Observation in Patients With Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER RCC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03055013
• Other study ID #: NCI-2016-00326
• Secondary ID: NCI-2016-00326EA
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 28, 2017
• Est. completion date: June 9, 2031

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase III trial compares nephrectomy (surgery to remove a kidney or part of a kidney) with nivolumab to the usual approach of nephrectomy followed by standard post-operative follow-up and monitoring, in treating patients with kidney cancer that is limited to a certain part of the body (localized). Nivolumab is a drug that may help stimulate the immune system to attack any cancer cells that may remain after surgery. The addition of nivolumab to the usual surgery could prevent the cancer from returning. It is not yet known whether nivolumab and nephrectomy is more effective than nephrectomy alone in treating patients with kidney cancer.

Description:

PRIMARY OBJECTIVE:

I. To compare recurrence-free survival (RFS) between patients with renal cell carcinoma randomly assigned to perioperative nivolumab in conjunction with radical or partial nephrectomy with patients randomized to surgery alone.

SECONDARY OBJECTIVES:

I. To evaluate for differences in recurrence-free survival associated with perioperative nivolumab compared to surgery alone among the subset of patients with clear cell histology.

II. To compare the overall survival between the two arms. III. To describe the safety and tolerability of perioperative nivolumab.

CORRELATIVE OBJECTIVES:

I. To correlate the primary tumor's expression of PD-L1 with outcome. II. To correlate the expression of PD-L1 on tumor tissue at nephrectomy and recurrence with outcome.

III. To archive images for potential central confirmation of recurrence and for future correlative work with American College of Radiology Imaging Network (ACRIN), including markers predicting outcome or response.

IV. To prospectively collect tumor and biologic specimens (e.g., serum, peripheral blood mononuclear cells [PBMCs]) for future correlative studies.

V. To characterize the pharmacokinetics of nivolumab and explore exposure response relationships with respect to safety and efficacy.

VI. To characterize the immunogenicity of nivolumab.

QUALITY OF LIFE OBJECTIVE:

I. To evaluate differences in change from baseline in patient-reported symptoms and toxicities among patients randomized to treatment with nivolumab compared to surgery alone.

OTHER EXPLORATORY OBJECTIVES:

I. To explore descriptively the efficacy of treatment with nivolumab in patients with non-clear cell (including unclassified) histologies.

II. To characterize the effects of nivolumab on bone metabolism and bone density.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and every 12 months for 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 819
• Est. completion date: June 9, 2031
• Est. primary completion date: May 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have a renal mass consistent with a clinical stage >= T2Nx renal cell carcinoma (RCC) or TanyN+ RCC for which radical or partial nephrectomy is planned

• If histological confirmation of RCC has not been done within 12 months prior to randomization, patient must be willing to undergo a core biopsy for this purpose if randomized to Arm A

• NOTE: This histologic confirmation can be a (1) standard of care diagnostic biopsy or (2) a research biopsy or a planned metastasectomy. Tissue must be obtained with results available prior to the neoadjuvant dose

• Patients randomized to Arm A: core tumor biopsy must have demonstrated RCC of any histology, including sarcomatoid, unclassified, or "unknown histology" (if preoperative biopsy was uninformative) with exception below for non-diagnostic biopsies

• If the biopsy performed following randomization clearly demonstrates a benign condition, oncocytoma or a different type of cancer that is not RCC, the patient is not eligible and must come off study

• A non-diagnostic biopsy is considered a good faith effort and does not need to be repeated unless deemed clinically necessary by the treating investigator

• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Patients with a prior RCC that was treated > 5 years before are eligible if the current tumor is consistent with a new primary in the opinion of the treating investigator

• Patients with bilateral synchronous RCCs are eligible if they can be resected or definitively treated at the same time or within a 12 week window from time of initial nephrectomy (partial or radical) or procedure and maintain adequate residual renal function; the patient is not eligible if both kidneys are to be completely removed and subsequent hemodialysis will be required

• Permitted forms of local therapy for second tumor:

• Partial or radical nephrectomy

• If kidney tumor is =< 3 cm: thermal ablation (e.g., radiofrequency ablation, cryoablation or stereotactic radiosurgery)

• Patient must have the ability to understand and the willingness to sign a written informed consent document

• White blood cells >= 2000/uL (within 8 weeks prior to randomization)

• Absolute neutrophil count (ANC) >= 1,500/mm^3 (within 8 weeks prior to randomization)

• Platelet count >= 100,000/mm^3 (within 8 weeks prior to randomization)

• Hemoglobin >= 9.0 g/dL (within 8 weeks prior to randomization)

• Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) >= 40mL/min (within 8 weeks prior to randomization)

• Total bilirubin =< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 x ULN) (within 8 weeks prior to randomization)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN (within 8 weeks prior to randomization)

Exclusion Criteria:

• Clinical or radiological evidence of distant metastases (M0) unless the presumed M1 disease is planned to be resected/definitively treated (e.g., thermal ablation, stereotactic radiation) at the same time or up to 12 weeks after the date of the initial procedure such that the patient is considered "no evidence of disease" (M1 NED)

• Liver, bone, or brain metastases are not permitted

• No more than 3 metastases are permitted, and all must be able to be removed or definitively treated within 12 weeks of the primary tumor resection

• Prior systemic or local anti-cancer therapy for the current RCC, including:

• Partial nephrectomy for the current RCC

• Metastasectomy for the current RCC diagnosis unless performed to render patient NED (in addition to the planned nephrectomy) within 6 months prior to the current diagnosis

• Current or past antineoplastic systemic therapies for RCC: i.e., chemotherapy, hormonal therapy, immunotherapy, or standard or investigational agents for treatment of RCC

• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways

• History of RCC that was treated with curative intent within the past 5 years

• Concurrent malignancies, with the following exceptions:

• Adequately treated basal cell or squamous cell skin cancer

• In situ cervical cancer

• A history of superficial Ta urothelial cancer is permitted (as long as not currently undergoing treatment) whereas T1 or greater disease is excluded if < 3 years from diagnosis; concurrent persistent disease is not permitted

• Adequately treated stage I or II cancer from which the patient is currently in complete remission

• Any other cancer and stage from which the patient has been disease-free for at least 3 years prior to the time of randomization and as long as they are not receiving any current treatment (e.g. adjuvant or maintenance systemic or local therapy)

• Concurrent low risk prostate cancer on active surveillance

• Active known or suspected autoimmune disease. The following autoimmune disorders are permitted: patients with vitiligo, type I diabetes mellitus, controlled/stable hypo or hyperthyroidism due to autoimmune or non-autoimmune conditions (hormone replacement is allowed), psoriasis not requiring systemic treatment, or other conditions not expected to recur

• Ongoing condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications with the exceptions outlined below

• Any treatment with other immunosuppressive agents within 14 days prior to the first dose of study drug with the following exceptions:

• Topical, ocular, intra-articular, intranasal, inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone or the equivalent are permitted in the absence of active autoimmune disease

• A brief (less than 3 weeks) course of corticosteroids (any amount) for prophylaxis (for example: contrast dye allergy) or for treatment of non-autoimmune conditions (for example: nausea, delayed-type hypersensitivity reaction caused by a contact allergen) is permitted

• Uncontrolled adrenal insufficiency

• Known evidence of chronic active liver disease or evidence of acute or chronic hepatitis B Virus (HBV) or hepatitis C (HCV); HBV and HCV testing must be completed within 8 weeks prior to randomization

• NOTE: If the patient has been treated and cured, and the HCV ribonucleic acid (RNA) is undetectable, the patient is eligible for this study

• Serious intercurrent illness, including ongoing or active infection requiring parenteral antibiotics

• Known evidence of human immunodeficiency virus (HIV) infection, since the effects of nivolumab on anti-retroviral therapy have not been studied; HIV testing is only required if past or current history is suspected

• Known medical condition (e.g. a condition associated with uncontrolled diarrhea such as ulcerative colitis or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results

• Major surgery within 28 days prior to randomization

• Concurrent enrollment in other clinical trials testing a therapeutic intervention

• History of severe hypersensitivity to a monoclonal antibody

• Pregnant or breast-feeding, as the effects of nivolumab on the developing human fetus or in the nursing infant are unknown; all patients of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a patient of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception, as described in the informed consent form (ICF), or by abstaining from sexual intercourse for the duration of their participation in the study; patients of childbearing potential must use adequate methods to avoid pregnancy for 5 months after the last dose of nivolumab

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma
• Sarcomatoid Renal Cell Carcinoma
• Stage II Renal Cell Cancer AJCC v7
• Stage III Renal Cell Cancer AJCC v7
• Unclassified Renal Cell Carcinoma

Intervention

Procedure:
• Nephrectomy
Undergo nephrectomy

Biological:
• Nivolumab
Given IV

Other:
• Patient Observation
Undergo observation

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	QEII Health Sciences Centre/Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Saint Joseph's Healthcare Charlton Campus	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	CHUM - Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	Niagara Health System-Saint Catharines General	Saint Catharines	Ontario
Canada	Centre Hospitalier Universitaire de Sherbrooke-Fleurimont	Sherbrooke	Quebec
Canada	Odette Cancer Centre- Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	Windsor Regional Cancer Centre	Windsor	Ontario
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Israel	Rambam Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Langlade Hospital and Cancer Center	Antigo	Wisconsin
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Harold Alfond Center for Cancer Care	Augusta	Maine
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	AIS Cancer Center at San Joaquin Community Hospital	Bakersfield	California
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Greater Baltimore Medical Center	Baltimore	Maryland
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana
United States	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Our Lady of the Lake Physicians Group - Medical Oncology	Baton Rouge	Louisiana
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Waldo County General Hospital	Belfast	Maine
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Beverly Hospital	Beverly	Massachusetts
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford	Biddeford	Maine
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Veterans Administration Medical Center - Birmingham	Birmingham	Alabama
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Lafayette Family Cancer Center-EMMC	Brewer	Maine
United States	Saint Joseph Mercy Brighton	Brighton	Michigan
United States	James J Peters VA Medical Center	Bronx	New York
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Ascension Southeast Wisconsin Hospital - Elmbrook Campus	Brookfield	Wisconsin
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Joseph Mercy Canton	Canton	Michigan
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Rex Hematology Oncology Associates-Cary	Cary	North Carolina
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ralph H Johnson VA Medical Center	Charleston	South Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Saint Joseph Mercy Chelsea	Chelsea	Michigan
United States	Saint Luke's Hospital	Chesterfield	Missouri
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Prisma Health Cancer Institute - Laurens	Clinton	South Carolina
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Community Cancer Institute	Clovis	California
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Memorial Hospital North	Colorado Springs	Colorado
United States	UCHealth Memorial Hospital Central	Colorado Springs	Colorado
United States	MU Health - University Hospital/Ellis Fischel Cancer Center	Columbia	Missouri
United States	UM Sylvester Comprehensive Cancer Center at Coral Gables	Coral Gables	Florida
United States	Northshore Oncology Associates-Covington	Covington	Louisiana
United States	Siteman Cancer Center at West County Hospital	Creve Coeur	Missouri
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Deerfield Beach	Deerfield Beach	Florida
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Elmhurst Memorial Hospital	Elmhurst	Illinois
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Sanford Roger Maris Cancer Center	Fargo	North Dakota
United States	Farmington Health Center	Farmington	Utah
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Simonds-Sinon Regional Cancer Center	Fitchburg	Massachusetts
United States	Aurora Health Center-Fond du Lac	Fond Du Lac	Wisconsin
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Cancer Care and Hematology-Fort Collins	Fort Collins	Colorado
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Parkview Regional Medical Center	Fort Wayne	Indiana
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Ascension Saint Francis - Reiman Cancer Center	Franklin	Wisconsin
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Gibbs Cancer Center-Gaffney	Gaffney	South Carolina
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	University of Texas Medical Branch	Galveston	Texas
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	Aurora Health Care Germantown Health Center	Germantown	Wisconsin
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Glens Falls Hospital	Glens Falls	New York
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Aurora Cancer Care-Grafton	Grafton	Wisconsin
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	UCHealth Greeley Hospital	Greeley	Colorado
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Gibbs Cancer Center-Pelham	Greer	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Gulfport Memorial Hospital	Gulfport	Mississippi
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Kaiser Permanente - Harbor City	Harbor City	California
United States	Hartford Hospital	Hartford	Connecticut
United States	HaysMed University of Kansas Health System	Hays	Kansas
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Edward Hines Jr VA Hospital	Hines	Illinois
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	Oncology Center of The South Incorporated	Houma	Louisiana
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Franciscan Health Indianapolis	Indianapolis	Indiana
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana
United States	Kaiser Permanente-Irvine	Irvine	California
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin
United States	Truman Medical Centers	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Kansas Cancer Center - North	Kansas City	Missouri
United States	Vidant Oncology-Kenansville	Kenansville	North Carolina
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Aurora Cancer Care-Kenosha South	Kenosha	Wisconsin
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Lakeland Regional Health Hollis Cancer Center	Lakeland	Florida
United States	The Watson Clinic	Lakeland	Florida
United States	Sparrow Hospital	Lansing	Michigan
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	OptumCare Cancer Care at Charleston	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kansas Cancer Center - Lee's Summit	Lee's Summit	Missouri
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Kaiser Permanente West Los Angeles	Los Angeles	California
United States	UCLA / Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Medical Center of the Rockies	Loveland	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	William S Middleton VA Medical Center	Madison	Wisconsin
United States	Aurora Bay Area Medical Group-Marinette	Marinette	Wisconsin
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Sovah Health Martinsville	Martinsville	Virginia
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	Bon Secours Memorial Regional Medical Center	Mechanicsville	Virginia
United States	Aspirus Medford Hospital	Medford	Wisconsin
United States	Rogue Valley Medical Center	Medford	Oregon
United States	Midstate Medical Center	Meriden	Connecticut
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	LSU Healthcare Network / Metairie Multi-Specialty Clinic	Metairie	Louisiana
United States	Miami Cancer Institute	Miami	Florida
United States	UM Sylvester Comprehensive Cancer Center at Kendall	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Woodland Cancer Care Center	Michigan City	Indiana
United States	UH Seidman Cancer Center at Southwest General Hospital	Middleburg Heights	Ohio
United States	Bon Secours Saint Francis Medical Center	Midlothian	Virginia
United States	Aurora Cancer Care-Milwaukee	Milwaukee	Wisconsin
United States	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin
United States	Aurora Sinai Medical Center	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Minneapolis VA Medical Center	Minneapolis	Minnesota
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Franciscan Health Mooresville	Mooresville	Indiana
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Edward Hospital/Cancer Center	Naperville	Illinois
United States	Meharry Medical College	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	The Hospital of Central Connecticut	New Britain	Connecticut
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Ascension Providence Hospitals - Novi	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Olathe Health Cancer Center	Olathe	Kansas
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Kaiser Permanente-Ontario	Ontario	California
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	VA Palo Alto Health Care System	Palo Alto	California
United States	Kaiser Permanente - Panorama City	Panorama City	California
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Ascension Via Christi - Pittsburg	Pittsburg	Kansas
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois
United States	UM Sylvester Comprehensive Cancer Center at Plantation	Plantation	Florida
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Miriam Hospital	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Aurora Cancer Care-Racine	Racine	Wisconsin
United States	Rex Hematology Oncology Associates-Blue Ridge	Raleigh	North Carolina
United States	UNC Rex Cancer Center of Wakefield	Raleigh	North Carolina
United States	UNC Rex Healthcare	Raleigh	North Carolina
United States	Eisenhower Medical Center	Rancho Mirage	California
United States	Renown Regional Medical Center	Reno	Nevada
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Vidant Oncology-Richlands	Richlands	North Carolina
United States	Bon Secours Saint Mary's Hospital	Richmond	Virginia
United States	Reid Health	Richmond	Indiana
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Kaiser Permanente-Riverside	Riverside	California
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Penobscot Bay Medical Center	Rockport	Maine
United States	Kaiser Permanente-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center at Saint Peters Hospital	Saint Peters	Missouri
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Audie L Murphy VA Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford	Sanford	Maine
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	South Jordan Health Center	South Jordan	Utah
United States	Maine Medical Partners - South Portland	South Portland	Maine
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Aurora Medical Center in Summit	Summit	Wisconsin
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	University of Kansas Health System Saint Francis Campus	Topeka	Kansas
United States	William Beaumont Hospital - Troy	Troy	Michigan
United States	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Vince Lombardi Cancer Clinic-Two Rivers	Two Rivers	Wisconsin
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	George Washington University Medical Center	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	Aspirus Regional Cancer Center	Wausau	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Ascension Medical Group Southeast Wisconsin - Mayfair Road	Wauwatosa	Wisconsin
United States	Aurora Cancer Care-Milwaukee West	Wauwatosa	Wisconsin
United States	Aurora West Allis Medical Center	West Allis	Wisconsin
United States	University of Cincinnati Cancer Center-West Chester	West Chester	Ohio
United States	Lexington Medical Center	West Columbia	South Carolina
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Dickstein Cancer Treatment Center	White Plains	New York
United States	Presbyterian Intercommunity Hospital	Whittier	California
United States	UPMC Susquehanna	Williamsport	Pennsylvania
United States	Winchester Hospital	Winchester	Massachusetts
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Aspirus Cancer Care - Wisconsin Rapids	Wisconsin Rapids	Wisconsin
United States	Kaiser Permanente-Woodland Hills	Woodland Hills	California
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Canadian Cancer Trials Group

Countries where clinical trial is conducted

United States,  Canada,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Association Between the Primary Tumor's Expression of PD-L1 With Outcome	Association between the primary tumor's expression of PD-L1 with outcome	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years
Other	Association Between the Expression of PD-L1 on Tumor Tissue at Nephrectomy as Well as Recurrence and Outcome	Association between the expression of PD-L1 on tumor tissue at nephrectomy as well as recurrence and outcome	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years
Other	To Archive Images for Potential Central Confirmation of Recurrence and for Future Correlative Work	To archive images for potential central confirmation of recurrence and for future correlative work	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years
Other	To Collect Tumor and Biologic Specimens for Future Correlative Studies	To collect tumor and biologic specimens for future correlative studies	Assessed at baseline, nephrectomy, 9 months and recurrence
Other	To Characterize the Pharmacokinetics of Nivolumab and Explore Exposure Response Relationships With Respect to Safety and Efficacy	To characterize the pharmacokinetics of nivolumab and explore exposure response relationships with respect to safety and efficacy	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years
Other	To Characterize the Immunogenicity of Nivolumab	To characterize the immunogenicity of nivolumab	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years
Other	To Evaluate Differences in Change From Baseline in Patient-reported Symptoms and Toxicities Among Patients Randomized to Treatment With Nivolumab Compared to Surgery Alone	To evaluate differences in change from baseline in patient-reported symptoms and toxicities among patients randomized to treatment with nivolumab compared to surgery alone	Assessed at baseline, pre-nephrectomy, 8 weeks post-nephrectomy, 20 weeks, 40 weeks, 54 weeks, recurrence and 2 years post randomization
Other	To Explore Descriptively the Efficacy of Treatment With Nivolumab in Patients With Non-clear Cell (Including Unclassified) Histologies.	To explore descriptively the efficacy of treatment with nivolumab in patients with non-clear cell (including unclassified) histologies.	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years
Other	To Characterize the Effects of Nivolumab on Bone Metabolism and Bone Density	To characterize the effects of nivolumab on bone metabolism and bone density	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years
Primary	Recurrence-free Survival (RFS) Rate at 5 Years	RFS is defined as time from randomization to disease recurrence or death from any cause. Patients who did not undergo nephrectomy or were not disease-free following nephrectomy were considered as having an event at day 1. Patients that are alive without an event were censored at the date of last disease evaluation. RFS rate at 5 years was the proportion of patients who are recurrence-free and alive at 5 years based on Kaplan-Meier estimates.	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years
Secondary	Recurrence-free Survival (RFS) Rate at 3 Years Among Patients With Clear Cell Histology	RFS is defined as time from randomization to disease recurrence or death from any cause. Patients who did not undergo nephrectomy or were not disease-free following nephrectomy were considered as having an event at day 1. Patients that are alive without an event were censored at the date of last disease evaluation. RFS rate at 3 years was the proportion of patients who are recurrence-free and alive at 3 years based on Kaplan-Meier estimates.	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 1 year
Secondary	Overall Survival Rate at 5 Years	Overall survival is defined as time from randomization to death from any cause. Overall survival rate at 5 years was the proportion of patients who are alive at 5 years based on Kaplan-Meier estimates.	Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years