Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Sunitinib or Sorafenib in Treating Patients With Kidney Cancer That Was Removed By Surgery

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Biomarker/Laboratory analysis, Treatment Active 18 and over NCI ECOG-E2805 E2805, CALGB-E2805, SWOG-E2805, CAN-NCIC-E2805, NCT00326898

Special Category: NCI Web site featured trial, CTSU trial

Objectives

Primary

1. Compare the disease-free survival of patients with locally advanced renal cell carcinoma treated with adjuvant sunitinib malate vs sorafenib vs placebo after radical or partial nephrectomy.

Secondary

1. Compare overall survival of patients treated with these regimens.
2. Define the toxicity of prolonged administration of sunitinib malate or sorafenib in these patients.
3. Assess angiogenesis markers in tissue, blood, and urine as predictors of disease-free survival and therapeutic benefit.
4. Assess the frequency of oncogene and tumor suppressor gene mutations as predictors of disease-free survival and therapeutic benefit.
5. Assess tumor and genetic polymorphisms as predictors of disease-free survival and therapeutic benefit.
6. Use DNA methylation profiles as predictors of outcome and therapeutic benefit.
7. Correlate polymorphisms in drug-metabolizing enzymes with steady-state concentrations of sorafenib or sunitinib malate in selected patients.
8. Study the effect of vascular endothelial growth factor-targeted therapy on circulating endothelial cells and circulating endothelial progenitors.
9. Evaluate cardiac function in a subset of patients.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed renal cell carcinoma, including any of the following subtypes:
  • Clear cell carcinoma
  • Nonclear cell carcinoma
    • No collecting duct or medullary carcinomas



• Meets 1 of the following risk categories:
  • Intermediate high-risk disease
    • pT1b, G3-4 N0 (or pNX where clinically N0) M0
    • pT2, G1-2 N0 (or pNX where clinically N0) M0
    • pT2, G3-4 N0 (or pNX where clinically N0) M0
    • pT3a, G1-2 (as long as pT3a is not due to adrenal involvement) N0 (or pNX where clinically N0) M0
    • Patients with microvascular invasion of the renal vein of pT1a-pT3a (as long as pT3a is not due to adrenal involvement and grade 1-2) N0 (or pNX where clinically N0) M0
  • Very high-risk disease
    • pT3a, G3-4 (or any grade pT3a if due to adrenal involvement) N0 (or pNX where clinically N0) M0
    • pT3b-c G any N0 (or pNX where clinically N0) M0
    • pT4 G N0 (or pNX where clinically N0) M0 any
    • pT any G any N+
    • Patients with microvascular invasion of the renal vein with above other characteristics



• Planning to start study treatment between 4-12 weeks after radical or partial nephrectomy
  • Underwent full surgical resection (i.e., radical or partial nephrectomy) by either open or laparoscopic technique within the past 3-10 weeks
    • Clinical evidence of lymph node positivity requires complete regional lymphadenectomy
    • All surgical specimens must have negative margins
  • Planning to undergo the above surgical resection AND meets all of the following criteria:
    • Primary intact renal cell carcinoma, eligible for nephrectomy with curative intent
    • pT1b-4, N0 or any fully resectable N (i.e., N1-2), M0 disease by radiologic criteria, meeting any of the following criteria:
      • Tumors ≥ 4 cm
      • Macroscopic fully resectable nodes
      • Surgically resectable renal vein thrombus
      • Surgically resectable inferior vena caval thrombus by radiologic criteria
    • Multifocal ipsilateral renal cell carcinoma allowed provided fully resectable and does not exceed inclusion criteria



• No evidence of residual or metastatic renal cell cancer by chest, abdomen, and pelvic CT scan with oral and IV contrast (or MRI scan of the abdomen and pelvis with gadolinium and a CT scan of the chest with or without IV contrast) within 4 weeks of randomization (after radical or partial nephrectomy)



• No history of distant metastases

Prior/Concurrent Therapy:

• Recovered from prior surgery
• No prior anticancer therapy for renal cell carcinoma in either the adjuvant or neoadjuvant setting, including any of the following:
  • Metastectomy
  • Radiotherapy to the renal bed
• At least 2 weeks since prior and no concurrent treatment with any of the following*:
  • Cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital)
  • Hypericum perforatum (St. John’s wort)
  • Ketoconazole
  • Dexamethasone
  • Dysrhythmic drugs (i.e., terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide)
  • Haloperidol
  • Risperidone
  • Rifampin
  • Grapefruit juice or grapefruit

   [Note: * Topical and inhaled steroids are allowed]

• Concurrent participation in protocol ECOG-E1Y03 allowed
• No other concurrent investigational anticancer agents

Patient Characteristics:

• ECOG performance status 0-1
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Creatinine ≤ 2.0 times upper limit of normal (ULN) OR creatinine clearance ≥ 30 mL/min
• Bilirubin ≤ 1.5 times ULN
• SGOT and SGPT ≤ 2.5 times ULN
• Absolute baseline LVEF ≥ 50% by MUGA within 4 weeks of randomization
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer, in situ cervical cancer, or ductal or lobular carcinoma in situ of the breast
• No serious intercurrent illness, including, but not limited to, any of the following:
  • Clinically significant cardiovascular disease(e.g., uncontrolled hypertension, myocardial infraction, or unstable angina)
  • New York Heart Association class II-IV congestive heart failure
  • Peripheral vascular disease ≥ grade 2
  • Psychiatric illness or social situation that would preclude study compliance
• At least 6 months since any of the following:
  • Myocardial infarction
  • Severe or unstable angina
  • Coronary or peripheral artery bypass graft
  • Symptomatic congestive heart failure
  • Cerebrovascular accident
  • Transient ischemic attack
  • Pulmonary embolism
• No ongoing ventricular cardiac dysrhythmias ≥ grade 2
• No ongoing atrial fibrillation
• No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation ≥ 3 beats in a row)
• QTc interval < 500 msec by baseline EKG
• No uncontrolled hypertension (i.e., diastolic blood pressure ≥ 100 mm Hg despite optimal medical therapy)
• No pre-existing thyroid abnormality with thyroid stimulating hormone that cannot be maintained in the normal range with medication
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known HIV infection
• Able to swallow pills

Expected Enrollment

A total of 1,332 patients will be accrued for this study.

Outcomes

Disease-free survival

Overall survival

Outline

This is a randomized, double-blind, multicenter study. Patients who have not had surgical resection undergo radical or partial nephrectomy first. Patients are then stratified according to risk (intermediate high-risk vs very high-risk), histology (clear cell vs non-clear cell [except collecting duct or medullary]), ECOG performance status (0 vs 1), and the type of nephrectomy (laparoscopic vs open). Patients are randomized to 1 of 3 treatment arms.

• Arm A: Patients receive oral sunitinib malate once daily for 4 weeks followed by rest for 2 weeks and oral placebo for sorafenib twice daily for 6 weeks.



• Arm B: Patients receive oral sorafenib twice daily for 6 weeks and oral placebo for sunitinib malate once daily for 4 weeks followed by rest for 2 weeks.



• Arm C: Patients receive oral placebo for sorafenib as in arm A and oral placebo for sunitinib malate as in arm B.

In all arms, treatment repeats every 6 weeks for up to 9 courses in the absence of disease progression or unacceptable toxicity.

Tumor tissue is collected prior to or during nephrectomy. Blood and urine samples are collected at baseline and periodically during study for biomarker correlative studies.

After completion of study treatment, patients are followed periodically for 9 years.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Naomi Balzer-Haas, MD, Protocol chair		Ph: 215-615-5121 Email: naomi.haas@uphs.upenn.edu
Keith Flaherty, MD, Protocol co-chair		Ph: 215-662-8624
Robert Uzzo, MD, Protocol co-chair		Ph: 215-728-3501; 888-369-2427

Cancer and Leukemia Group B

Christopher Kane, MD, Protocol chair		Ph: 415-353-7171; 800-888-8664

Southwest Oncology Group

Christopher Wood, MD, Protocol chair		Ph: 713-792-3250; 800-392-1611

NCIC-Clinical Trials Group

Michael Jewett, MD, Protocol chair		Ph: 416-946-2903 Email: m.jewett@utoronto.ca

U.S.A.
Alabama
	Birmingham
	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
		Clinical Trials Office - Lurleen Wallace Comprehensive Cancer	Ph:  205-934-0309
	Huntsville
	Clearview Cancer Institute
		Clinical Trials Office - Clearview Cancer Institute	Ph:  256-705-4224
	Mobile
	Providence Cancer Center at Providence Hospital
		Paul Schwarzenberger, MD	Ph:  251-544-1013
Alaska
	Anchorage
	Providence Cancer Center
		Clinical Trials Office - Providence Cancer Center	Ph:  907-261-3109
	Fairbanks
	Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
		Jacqueline Vuky	Ph:  907-458-5380 800-678-5458
Arizona
	Scottsdale
	Mayo Clinic Scottsdale
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
	Tucson
	Arizona Cancer Center at University of Arizona Health Sciences Center
		Clinical Trials Office - Arizona Cancer Center at University of Arizona Health Sciences Center	Ph:  520-626-9008
Arkansas
	Bentonville
	Highlands Oncology Group - Springdale
		Joseph Beck, MD, FACP	Ph:  479-587-1700
	Hot Springs
	St. Joseph's Mercy Cancer Center
		Prabhakara Reddy	Ph:  501-623-2731
	Little Rock
	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
		Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Ph:  501-686-8274
California
	Berkeley
	Alta Bates Summit Comprehensive Cancer Center
		Clinical Trials Office - Alta Bates Summit Comprehensive Cancer Center	Ph:  510-204-3428
	Burbank
	Providence Saint Joseph Medical Center - Burbank
		Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank	Ph:  818-847-3220
	Burlingame
	Peninsula Medical Center
		David Irwin, MD	Ph:  510-204-1591
	Castro Valley
	East Bay Radiation Oncology Center
		James Feusner, MD	Ph:  510-428-3689
	Eden Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Castro Valley
		James Feusner, MD	Ph:  510-428-3689
	Concord
	Cancer Care Center at John Muir Health - Concord Campus
		Clinical Trials Office - Cancer Care Center at John Muir Health - Concord Campus	Ph:  925-674-2580
	Duarte
	City of Hope Comprehensive Cancer Center
		Clinical Trials Office - City of Hope Comprehensive Cancer Center	Ph:  800-826-4673
			Email: becomingapatient@coh.org
	Fairfield
	North Bay Cancer Center
		Clinical Trials Office - North Bay Cancer Center	Ph:  707-429-6976
	Fremont
	Kaiser Permanente - Fremont
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Valley Medical Oncology
		James Feusner, MD	Ph:  510-428-3689
	Fullerton
	Virginia K. Crosson Cancer Center at St. Jude Medical Center
		Clinical Trials Office - Virginia K. Crosson Cancer Center	Ph:  714-446-5642
	Greenbrae
	California Cancer Care, Incorporated - Greenbrae
		Peter Eisenberg, MD	Ph:  415-925-5000
	Marin Cancer Institute at Marin General Hospital
		David Irwin, MD	Ph:  510-204-1591
	Sutter Health - Western Division Cancer Research Group
		David Irwin, MD	Ph:  510-204-1591
	Hayward
	Kaiser Permanente Medical Center - Hayward
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
	Martinez
	Contra Costa Regional Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Modesto
	Memorial Medical Center
		Clinical Trials Office - Memorial Medical Center	Ph:  209-572-7116
	Monterey
	Community Hospital of the Monterey Peninsula Comprehensive Cancer Center
		Thomas Bradley, MD, PhD, FACP	Ph:  831-375-4777
	Mountain View
	Camino Medical Group - Treatment Center
		Peter Yu, MD	Ph:  408-524-5814
	Oakland
	Alta Bates Summit Medical Center - Summit Campus
		Clinical Trials Office - Alta Bates Summit Medical Center - Summit Campus	Ph:  510-204-1414
	Bay Area Breast Surgeons, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	CCOP - Bay Area Tumor Institute
		James Feusner, MD	Ph:  510-428-3689
	Highland General Hospital
		James Feusner, MD	Ph:  510-428-3689
	Kaiser Permanente Medical Center - Oakland
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Larry G Strieff MD Medical Corporation
		James Feusner, MD	Ph:  510-428-3689
	Tom K Lee, Incorporated
		James Feusner, MD	Ph:  510-428-3689
	Orange
	Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
		Clinical Trials Office - Chao Family Comprehensive Cancer Center	Ph:  877-UC-STUDY
			Email: ucstudy@uci.edu
	St. Joseph Hospital Regional Cancer Center - Orange
		Timothy Byun	Ph:  714-771-8999
	Palo Alto
	Palo Alto Medical Foundation
		David Leibowitz	Ph:  650-321-4121
	Pleasanton
	Valley Care Medical Center
		James Feusner, MD	Ph:  510-428-3689
	Valley Medical Oncology Consultants - Pleasanton
		James Feusner, MD	Ph:  510-428-3689
	Redwood City
	Kaiser Permanente Medical Center - Redwood City
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Richmond
	Kaiser Permanente Medical Center - Richmond
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Roseville
	Kaiser Permanente Medical Center - Roseville
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sacramento
	Kaiser Permanente Medical Center - Sacramento
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South Sacramento Kaiser-Permanente Medical Center
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	University of California Davis Cancer Center
		Clinical Trials Office - University of California Davis Cancer Center	Ph:  916-734-3089
	Salinas
	Salinas Valley Memorial Hospital
		Shehzad Aziz, MD	Ph:  831-755-1701
	San Diego
	Kaiser Permanente Medical Office -Vandever Medical Office
		Jonathan Polikoff, MD	Ph:  619-528-5888
	Veterans Affairs Medical Center - San Diego
		Barbara Parker	Ph:  858-552-8585
	San Francisco
	California Pacific Medical Center - California Campus
		David Irwin, MD	Ph:  510-204-1591
	Kaiser Permanente Medical Center - San Francisco Geary Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
	San Jose
	Kaiser Permanente Medical Center - Santa Teresa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	San Pablo
	Doctors Medical Center - San Pablo Campus
		James Feusner, MD	Ph:  510-428-3689
	San Rafael
	Kaiser Foundation Hospital - San Rafael
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Clara
	Kaiser Permanente Medical Center - Santa Clara Kiely Campus
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Santa Rosa
	Kaiser Permanente Medical Center - Santa Rosa
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	South San Francisco
	Kaiser Permanente Medical Center - South San Francisco
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Stanford
	Stanford Cancer Center
		Clinical Trials Office - Stanford Cancer Center	Ph:  650-498-7061
			Email: cctoffice@stanford.edu
	Stockton
	Kaiser Permanente Medical Facility - Stockton
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Vallejo
	Kaiser Permanente Medical Center - Vallejo
		Louis Fehrenbacher, MD	Ph:  707-651-2577
	Sutter Solano Medical Center
		David Irwin, MD	Ph:  510-204-1591
	Walnut Creek
	John Muir/Mt. Diablo Comprehensive Cancer Center
		Clinical Trials Office - John Muir/Mt. Diablo Comprehensive Cancer Center	Ph:  925-941-4246
	Kaiser Permanente Medical Center - Walnut Creek
		Louis Fehrenbacher, MD	Ph:  707-651-2577
Colorado
	Aurora
	Aurora Presbyterian Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	University of Colorado Cancer Center at UC Health Sciences Center
		Clinical Trials Office - University of Colorado Cancer Center	Ph:  720-848-0650
	Colorado Springs
	Memorial Hospital Cancer Center - Colorado Springs
		Clinical Trials Office - Memorial Hospital	Ph:  719-365-2406
	Penrose Cancer Center at Penrose Hospital
		Clinical Trials Office - Penrose Cancer Center	Ph:  719-776-5275
	Denver
	CCOP - Colorado Cancer Research Program
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Denver Health Medical Center
		Francis Gamza	Ph:  303-436-6000
	Porter Adventist Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Presbyterian - St. Luke's Medical Center
		Clinical Trials Office - Presbyterian - St. Luke's Medical Center	Ph:  303-839-6000
	Rose Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	St. Anthony Central Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	St. Joseph Hospital
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Edwards
	Shaw Regional Cancer Center
		Francis Gamza	Ph:  970-569-7429
	Englewood
	Swedish Medical Center
		Eduardo Pajon, MD	Ph:  303-399-8020ext2261
	Fort Collins
	Front Range Cancer Specialists
		Diana Medgyesy, MD	Ph: