A Study to Compare Treatments for a Type of Kidney Cancer Called TFE/Translocation Renal Cell Carcinoma (tRCC)

Metastatic Renal Cell Carcinoma Clinical Trial

Official title:

A Randomized Phase 2 Trial of Axitinib/Nivolumab Combination Therapy vs. Single Agent Nivolumab for the Treatment of TFE/Translocation Renal Cell Carcinoma (tRCC) Across All Age Groups

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03595124
• Other study ID #: NCI-2018-01489
• Secondary ID: NCI-2018-01489AR
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 8, 2019
• Est. completion date: September 30, 2027

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 II trial studies how well axitinib and nivolumab work in treating patients with TFE/translocation renal cell carcinoma that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Axitinib 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. Giving axitinib and nivolumab may work better in treating patients with TFE/translocation renal cell carcinoma compared to standard treatment, including surgery, chemotherapy, or immunotherapy.

Description:

PRIMARY OBJECTIVE: I. To establish the clinical activity, assessed primarily by progression-free survival, of nivolumab therapy with or without axitinib for advanced transcription factor E3/translocation morphology renal cell carcinoma (TFE/tRCC). SECONDARY OBJECTIVE: I. To further define the toxicities of the study arms in the treatment of translocation morphology RCC across all ages. EXPLORATORY OBJECTIVES: I. To characterize tRCC clinical behavior across all age groups. II. To evaluate type of antitumor immune response and stability of T cell activation before and after treatment with immunotherapy or antiangiogenic therapy. III. To develop a tumor bank of tRCC tumor samples treated on study for further biological investigations. IV. To characterize the pharmacokinetics of axitinib when given in combination with nivolumab in pediatric patients with tRCC. OUTLINE: Patients are now randomized to 1 of 2 arms - Arm A or Arm C. ARM A: Patients receive axitinib orally (PO) twice daily (BID) on days 1-28 and nivolumab intravenously (IV) over 30 minutes, or per institutional guidelines, on days 1 and 15 (if < 18 years old) or on day 1 (if >= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive axitinib PO BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL AS OF 1/23/2020 - PROSPECTIVE PATIENTS ARE RANDOMLY ASSIGNED TO ARMS A OR C) ARM C: Patients receive nivolumab IV over 30 minutes, or per institutional guidelines, on days 1 and 15 (if < 18 years old) or on day 1 (if >= 18 years old). Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and every 6 months for 2 years. Follow-up at year 5 and beyond is at the discretion of the treating physician.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months and older

Eligibility

Inclusion Criteria:

• Patients must be >= 12 months at enrollment
• Patients must have a body surface area (BSA) >= 0.53 m^2
• Histologically confirmed unresectable or metastatic translocation morphology renal cell carcinoma diagnosed using World Health Organization (WHO)-defined criteria. Patients may be newly diagnosed or have received prior cancer therapy
• Patients must have had histologic verification of the malignancy
• Patients must have measurable disease, documented by clinical, radiographic, or histologic criteria as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Patients must have a tumor showing the appropriate morphologic appearance, and either confirmed TFE3 nuclear protein expression by immunohistochemistry with appropriate positive and negative controls performed at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, or evidence of TFE3 or TFEb translocation by either fluorescence in situ hybridization (FISH) or reverse transcriptase- polymerase chain reaction (RT-PCR) performed at a CLIA-certified laboratory. For TFE3 immunohistochemistry, any nuclear positivity in the presence of appropriate positive and negative controls should be considered as evidence of TFE3 immunohistochemical expression. NOTE: If the institution is unable to perform these studies, unstained slides may be submitted to Dr. Elizabeth Perlman, who will perform TFE3 analysis at no charge. The slide will be returned to the referring institution for local evaluation, to be included in their institutional report
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Patients must have a life expectancy of >= 8 weeks
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (6 weeks if prior nitrosourea)
• Immunotherapy: Must not have received within 4 weeks of entry onto this study
• Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent
• Radiation therapy (RT): >= 2 weeks for local palliative RT (small port); >= 6 months must have elapsed if prior craniospinal RT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (performed within 7 days prior to enrollment)
• Platelet count >= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (performed within 7 days prior to enrollment)
• Urine protein: =< 30 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hours (h) urine sample (performed within 7 days prior to enrollment)
• For patients < 18 years of age: Serum creatinine =< 1.5 x upper limit of normal (ULN), or measured or calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 for patient with creatinine levels > 1.5 x institutional ULN, or a serum creatinine based on age/gender as follows (performed

within 7 days prior to enrollment):

• 1 to < 2 years - 0.6 mg/dL (male, female)
• 2 to < 6 years - 0.8 mg/dL (male, female)
• 6 to < 10 years - 1 mg/dL (male, female)
• 10 to < 13 years - 1.2 mg/dL (male, female)
• 13 to < 16 years - 1.5 mg/dL (male), 1.4 mg/dL (female)
• >= 16 years - 1.7 mg/dL (male), 1.4 mg/dL (female)
• Creatinine clearance should be calculated per institutional standard
• For patients >= 18 years of age: Serum creatinine =< 2 x ULN, or measured or calculated creatinine clearance or radioisotope GFR >= 40 mL/min/1.73 m^2 for patient with creatinine levels > 2 x institutional ULN (performed within 7 days prior to enrollment)
• Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin =< 1.5 x ULN for age, or direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 X ULN (performed within 7 days prior to enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN for age (performed within 7 days prior to enrollment)
• Albumin > 2.5 mg/dL (performed within 7 days prior to enrollment)
• Shortening fraction of >= 27% by echocardiogram, or
• Ejection fraction of >= 50% by radionuclide angiogram
• No history of myocardial infarction, severe or unstable angina, or peripheral vascular disease
• Corrected QT (QTc) =< 480 msec. Note: Patients with grade 1 prolonged QTc (450-480 msec) at the time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN. However, if patient is receiving anticoagulant therapy, PT or partial thromboplastin time (PTT) should be within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• A baseline blood pressure (BP) =< the 95th percentile for age, height, and gender for patients < 18 years old, or =< 150 mmHg (systolic) and =< 90 mmHg (diastolic) for patients >= 18 years old
• Note: 2 serial blood pressures should be taken at least 1 hour apart and averaged to determine baseline BP
• Patients are eligible if on stable doses (>= 7 days) of anti-hypertensive medications with a baseline BP meeting the criteria above

Exclusion Criteria:

• Patients unable to swallow whole tablets
• Patients who in the opinion of the investigator are not able to comply with the study procedures are not eligible
• Prior Therapy
• Patients who have received prior therapy with axitinib, nivolumab, or other PD1/PD-L1 targeted therapies
• Patients who have received prior therapy with more than one anti VEGF based agent (antibody or tyrosine kinase inhibitor)
• Patients with hypersensitivity to axitinib, nivolumab, or any of its excipients
• Patients who previously received an allogeneic stem cell transplant (SCT) or solid organ transplant are not eligible
• Patients may not be receiving any other investigational agents (within 4 weeks prior to study enrollment)
• Patients who have received prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study enrollment or who have not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks prior to enrollment
• Surgery: Patients who have had or who are planning to have the following invasive

procedures are not eligible:

• Major surgical procedure, laparoscopic procedure, open biopsy, core biopsy, fine needle aspirate, or significant traumatic injury within 7 days prior to enrollment. NOTE: External central lines must be placed at least 3 days prior to planned treatment initiation and subcutaneous ports must be placed at least 7 days prior to planned treatment initiation
• Patients who are planning cytoreductive surgery within the first 12 weeks following therapy initiation
• Patients who have a serious or non-healing wound or ulcer at the time of study enrollment are not eligible
• Patients who have a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study enrollment are not eligible
• Patients who have received prior targeted small molecule therapy within 2 weeks of enrollment or have not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks prior to enrollment. NOTE: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Pre-existing conditions, which may include:
• Additional known malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
• Patients with underlying immune deficiency, chronic infections including hepatitis, tuberculosis (TB), or autoimmune disease
• Human immunodeficiency virus (HIV)-infected patients with the exception of patients on an effective anti-retroviral therapy with an undetectable viral load within 6 months prior to enrollment
• Patients with underlying hematologic issues including congenital bleeding diathesis, known previous gastrointestinal (GI) bleeding requiring intervention within the past 6 months, history of hemoptysis within 42 days prior to study enrollment, active pulmonary emboli, or deep vein thromboses (DVT) that are not stable on anticoagulation regimen
• Patients must not have had significant vascular disease (i.e. Moya-Moya, aortic aneurysm requiring surgical repair)
• A known history of, or any evidence of active, non-infectious pneumonitis
• Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to study enrollment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study enrollment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• Any uncontrolled, intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia
• Any serious medical or psychiatric illness/condition including substance use disorders likely in the judgment of the investigator(s) to interfere or limit compliance with study requirements/treatment
• Patients with active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Treatments and/or medications the patient is receiving or has received that would make

her/him ineligible, including:

• Concomitant (or receipt of) treatment with medications that may affect the metabolism of nivolumab and/or axitinib within 7 days prior to planned first dose of protocol therapy
• A live vaccine within 30 days of planned first dose of protocol therapy. NOTE:

Inactivated flu vaccines are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed

• Pregnancy and breast feeding
• Due to risks of fetal and teratogenic adverse events as seen in animal studies, a negative pregnancy test must be obtained in females of childbearing potential, defined as females who are post-menarchal. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Females of childbearing potential that are sexually active must agree to either practice 2 medically accepted highly-effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 5 months after the last dose of study drug
• Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy through 5 months after the last dose of study therapy
• Male patients of reproductive potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy. Prior history of vasectomy does not replace requirement for contraceptive use
• Regulatory requirements
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma
• Stage III Renal Cell Cancer AJCC v8
• Stage IV Renal Cell Cancer AJCC v8
• Unresectable Renal Cell Carcinoma

Intervention

Drug:
• Axitinib
Given PO

Biological:
• Nivolumab
Given IV

Locations

Country	Name	City	State
Puerto Rico	HIMA San Pablo Oncologic Hospital	Caguas
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	Kaiser Permanente-Anaheim	Anaheim	California
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	PCR Oncology	Arroyo Grande	California
United States	Mission Hospital	Asheville	North Carolina
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	Overlake Medical Center	Bellevue	Washington
United States	Kaiser Permanente-Bellflower	Bellflower	California
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Harrison Medical Center	Bremerton	Washington
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Maimonides Medical Center	Brooklyn	New York
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Minnesota Oncology - Burnsville	Burnsville	Minnesota
United States	Cambridge Medical Center	Cambridge	Minnesota
United States	Mercy Cancer Center - Carmichael	Carmichael	California
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Carson Tahoe Regional Medical Center	Carson City	Nevada
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Memorial Hospital	Chattanooga	Tennessee
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	Bethesda North Hospital	Cincinnati	Ohio
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Prisma Health Cancer Institute - Laurens	Clinton	South Carolina
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Carle at The Riverfront	Danville	Illinois
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Kaiser Permanente Downey Medical Center	Downey	California
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	El Paso Children's Hospital	El Paso	Texas
United States	Mercy Cancer Center - Elk Grove	Elk Grove	California
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Saint Francis Hospital	Federal Way	Washington
United States	Kaiser Permanente-Fontana	Fontana	California
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Unity Hospital	Fridley	Minnesota
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Mountain Blue Cancer Care Center	Golden	Colorado
United States	CTCA at Western Regional Medical Center	Goodyear	Arizona
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin
United States	Saint Vincent Hospital Cancer Center Green Bay	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	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Cancer and Blood Specialists-Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	GenesisCare USA - Henderson	Henderson	Nevada
United States	Las Vegas Cancer Center-Henderson	Henderson	Nevada
United States	Las Vegas Urology - Green Valley	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Urology Specialists of Nevada - Green Valley	Henderson	Nevada
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Clare Hospital	Lakewood	Washington
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Ann M Wierman MD LTD	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada
United States	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada
United States	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Desert West Surgery	Las Vegas	Nevada
United States	GenesisCare USA - Fort Apache	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
United States	GenesisCare USA - Vegas Tenaya	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada
United States	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada
United States	Las Vegas Urology - Sunset	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	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Cancer Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Northwest	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Southwest	Las Vegas	Nevada
United States	Saint Joseph Hospital	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado
United States	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California
United States	Mattel Children's Hospital UCLA	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	Norton Children's Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Holy Family Memorial Hospital	Manitowoc	Wisconsin
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Saint Vincent Hospital Cancer Center at Marinette	Marinette	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	Health Partners Inc	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Saint Joseph Mount Sterling	Mount Sterling	Kentucky
United States	The Children's Hospital at TriStar Centennial	Nashville	Tennessee
United States	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	New Ulm Medical Center	New Ulm	Minnesota
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Saint Vincent Hospital Cancer Center at Oconto Falls	Oconto Falls	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hematology and Oncology Consultants PC	Omaha	Nebraska
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	Children's Hospital of Orange County	Orange	California
United States	Nemours Children's Hospital	Orlando	Florida
United States	Hope Cancer Care of Nevada-Pahrump	Pahrump	Nevada
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	Rocky Mountain Cancer Centers-Parker	Parker	Colorado
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Huron Medical Center PC	Port Huron	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Legacy Emanuel Children's Hospital	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Fairview Northland Medical Center	Princeton	Minnesota
United States	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Cancer Care Specialists - Reno	Reno	Nevada
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mercy Cancer Center - Rocklin	Rocklin	California
United States	Mercy Cancer Center - Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Children's Hospital of San Antonio	San Antonio	Texas
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Lakeview Hospital	Stillwater	Minnesota
United States	Saint Vincent Hospital Cancer Center at Sturgeon Bay	Sturgeon Bay	Wisconsin
United States	ProMedica Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Cancer Treatment Centers of America	Tulsa	Oklahoma
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Children's National Medical Center	Washington	District of Columbia
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	Woodland Memorial Hospital	Woodland	California
United States	Fairview Lakes Medical Center	Wyoming	Minnesota
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Translocation morphology renal cell carcinoma clinical behavior	Will list and summarize the frequency of site(s) of disease at presentation (including extent of lymph node involvement), site(s) of relapse, surgical practices on protocol therapy, and radiotherapy practices on protocol therapy.	Up to 4 years
Other	Type of antitumor immune response and stability of T cell activation	Will summarize the levels of analytes and tumor expression before and after treatment and evaluate the changes due to treatment after logarithmic transformation using the paired t-test. Analytes include myeloid derived stem cells: CD45, CD11b, CD33, CD14, CD15, HLA-DR, viability, stain 1; regulatory T cells: viability, CD45, CE4, CD3, CD24, FoxP3; CD8 T cells (CD45, CD8, CD3); CD8 phenotype and activation and exhaustion (CD69, CD38, PD1, CD244, TIM3). Tumor expression of PDL-1, PD1, CD3, CD4 and CD8 will be assessed using TFE renal cell carcinoma samples from the study and scored for intensity (0-3).	Baseline up to 4 years
Other	Pharmacokinetics (PK) of axitinib		Up to 4 years
Primary	Progression free survival		From randomization to the earliest of disease progression (according to Response Evaluation Criteria in Solid Tumors adapted for immunotherapy) or death due to any cause, assessed up to 4 years
Secondary	Overall survival	A stratified, one-sided log-rank test (using the stratification factors at randomization, age and prior therapy) will be performed to compare treatment arms with alpha = 0.05. Cox proportional hazards models will also be fit to evaluate the final hazard ratio between the treatment arms, with exploratory modeling taking into account the potential influence of other factors (e.g., baseline disease burden, upfront versus delayed nephrectomy). From these models, the hazard ratio for treatment assignment will be reported with a 90% confidence interval (to align with the overall alpha level of the primary log-rank test).	From randomization to death due to any cause, assessed up to 4 years
Secondary	Overall response rate (ORR)	Will be defined as the rate of complete or partial responses (assessed by imaging) among patients who initiated protocol therapy and completed at least one subsequent imaging assessment. A logistic regression model for overall response, stratified by the stratification factors used at randomization (age and prior therapy) will be fit, including treatment arm as a key covariate. From this model, the odds ratio for treatment arm will be reported with a 90% confidence interval. The ORR observed within each treatment arm will also be reported.	Up to 4 years
Secondary	Incidence of adverse events (AEs)	All grade 3 non-hematologic toxicities and all grade 4-5 or higher adverse events occurring during protocol therapy or within 30 days of treatment discontinuation will be analyzed. The rates of these events will be reported separately by treatment arm with 95% exact confidence intervals, both by individual AE and class of AE (e.g., hematologic). Given that some AEs may be rare, Fisher Exact tests will be used to test for statistical significance among any apparent differences by treatment arm.	Within 30 days of treatment discontinuation