Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery (ASSURE)

• ClinicalTrials.gov Identifier: NCT00326898
• Recruitment Status: Completed
• First Posted: May 17, 2006
• Results First Posted: December 12, 2016
• Last Update Posted: July 7, 2020
• Sponsor: National Cancer Institute (NCI)
• Collaborators: Cancer and Leukemia Group B; NCIC Clinical Trials Group; Southwest Oncology Group
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Clear Cell Renal Cell Carcinoma; Stage I Renal Cell Cancer AJCC v6 and v7; Stage II Renal Cell Cancer AJCC v7; Stage III Renal Cell Cancer AJCC v7
• Interventions: Other: Laboratory Biomarker Analysis; Other: Placebo; Other: Quality-of-Life Assessment; Drug: Sorafenib Tosylate; Drug: Sunitinib Malate
• Enrollment: 1943

Participant Flow

Recruitment Details	The study was activated on April 24, 2006 and closed to accrual on September 1, 2010, after accrual of 1943 patients.
Pre-assignment Details

Arm/Group Title	Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)
Arm/Group Description	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate 37.5mg PO QD for 4 weeks and placebo sorafenib tosylate 400mg PO QD or BID for 6 weeks.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate 400mg PO QD or BID for 6 weeks and placebo sunitinib malate 37.5mg PO QD for 4 weeks followed.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate 400mg as in Arm A and placebo sunitinib malate 37.5mg as in Arm B.
Period Title: Overall Study
Started	647	649	647
Patients With Toxicity Data	625	628	626
Patients With Clear Cell Histology	542	540	540
Patients With >=1 Follow-up MUGA Scan	513	510	580
Completed	296	306	444
Not Completed	351	343	203
Reason Not Completed
Disease progression	52	54	102
Adverse Event	124	128	33
Death	2	0	0
Withdrawal by Subject	134	128	32
Alternative therapy	1	0	0
Other complicating disease	5	5	4
Other/Missing/Unknown	33	28	32

Baseline Characteristics

Arm/Group Title		Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)	Total
Arm/Group Description		Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate 37.5mg PO QD for 4 weeks and placebo sorafenib tosylate 400mg PO QD or BID for 6 weeks.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate 400mg PO QD or BID for 6 weeks and placebo sunitinib malate 37.5mg PO QD for 4 weeks followed.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate 400mg as in Arm A and placebo sunitinib malate 37.5mg as in Arm B.	Total of all reporting groups
Overall Number of Baseline Participants		647	649	647	1943
Baseline Analysis Population Description		All randomized patients
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	647 participants	649 participants	647 participants	1943 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	489 75.6%	507 78.1%	500 77.3%	1496 77.0%
	>=65 years	158 24.4%	142 21.9%	147 22.7%	447 23.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	647 participants	649 participants	647 participants	1943 participants
	Female	218 33.7%	212 32.7%	204 31.5%	634 32.6%
	Male	429 66.3%	437 67.3%	443 68.5%	1309 67.4%

Outcome Measures

1. Primary Outcome

Title	Disease-free Survival (DFS)
Description	Disease-free survival (DFS) is defined as time from randomization to recurrence, development of second primary cancer (except localized breast or prostate cancer or nonmelanoma skin cancer), or death from any cause. Patients who were alive without recurrence or qualifying second primary cancer were censored at the date of last disease evaluation.
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry

Outcome Measure Data

Analysis Population Description

All randomized patients

Arm/Group Title	Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)
Arm/Group Description:	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate 37.5mg PO QD for 4 weeks and placebo sorafenib tosylate 400mg PO QD or BID for 6 weeks.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate 400mg PO QD or BID for 6 weeks and placebo sunitinib malate 37.5mg PO QD for 4 weeks followed.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate 400mg as in Arm A and placebo sunitinib malate 37.5mg as in Arm B.
Overall Number of Participants Analyzed	647	649	647
Median (97.5% Confidence Interval); Unit of Measure: years
	5.8 [1]; (5.0 to NA)	6.1 [1]; (4.8 to NA)	6.6; (5.3 to 7.8)

[1]

The upper limit of the 97.5% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Sunitinib + Sorafenib Placebo), Arm C (Sunitinib Placebo + Sorafenib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.80
	Comments	[Not Specified]
	Method	Stratified logrank test
	Comments	Stratified logrank test was performed. Stratification factors include basis of risk group, histologic subtype, performance status and type of surgery.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 97.5%; 0.85 to 1.23
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Sorafenib + Sunitinib Placebo), Arm C (Sunitinib Placebo + Sorafenib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.72
	Comments	[Not Specified]
	Method	Stratified logrank test
	Comments	Stratified logrank test was performed. Stratification factors include basis of risk group, histologic subtype, performance status and type of surgery.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 97.5%; 0.80 to 1.17
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	5-year Overall Survival Rate
Description	Overall survival is defined as the time from randomization to death from any cause. Patients without a date of death were censored at the date of last contact. Kaplan-Meier method was used to estimate 5-year survival rate.
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry

Outcome Measure Data

Analysis Population Description

All randomized patients

Arm/Group Title	Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)
Arm/Group Description:	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate 37.5mg PO QD for 4 weeks and placebo sorafenib tosylate 400mg PO QD or BID for 6 weeks.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate 400mg PO QD or BID for 6 weeks and placebo sunitinib malate 37.5mg PO QD for 4 weeks followed.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate 400mg as in Arm A and placebo sunitinib malate 37.5mg as in Arm B.
Overall Number of Participants Analyzed	647	649	647
Measure Type: Number; Number (97.5% Confidence Interval); Unit of Measure: proportion of participants
	0.779; (0.741 to 0.819)	0.805; (0.768 to 0.842)	0.803; (0.767 to 0.840)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Sunitinib + Sorafenib Placebo), Arm C (Sunitinib Placebo + Sorafenib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 97.5%; 0.90 to 1.52
	Estimation Comments	Hazard ratio was estimated using stratified proportional hazards model with Arm C (placebo arm) as the reference group.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B (Sorafenib + Sunitinib Placebo), Arm C (Sunitinib Placebo + Sorafenib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 97.5%; 0.75 to 1.28
	Estimation Comments	Hazard ratio was estimated using stratified proportional hazards model with Arm C (placebo arm) as the reference group.

3. Secondary Outcome

Title	Proportion of Patients With Cardiac Events
Description	Cardiac event is defined as left ventricular ejection fraction (LVEF) below the institutional lower limit of normal, where the decrease was >15% absolute percentage points from baseline within 6 months.
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry

Outcome Measure Data

Analysis Population Description

Patients with at least 1 follow-up MUGA scan were included in this analysis.

Arm/Group Title	Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)
Arm/Group Description:	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate 37.5mg PO QD for 4 weeks and placebo sorafenib tosylate 400mg PO QD or BID for 6 weeks.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate 400mg PO QD or BID for 6 weeks and placebo sunitinib malate 37.5mg PO QD for 4 weeks followed.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate 400mg as in Arm A and placebo sunitinib malate 37.5mg as in Arm B.
Overall Number of Participants Analyzed	513	510	580
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: Proportion of participants
	0.017; (0.009 to 0.030)	0.013; (0.006 to 0.026)	0.008; (0.003 to 0.018)

4. Secondary Outcome

Title	5-year Disease-free Survival (DFS) Rate Among Patients With Clear Cell Histology
Description	Disease-free survival (DFS) is defined as time from randomization to recurrence, development of second primary cancer (except localized breast or prostate cancer or nonmelanoma skin cancer), or death from any cause. Patients who were alive without recurrence or qualifying second primary cancer were censored at the date of last disease evaluation. 5-year DFS rate is the proportion of patients who are alive and disease-free at 5 years based on the Kaplan-Meier estimate.
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry

Outcome Measure Data

Analysis Population Description

Patients with clear cell histology were included in this analysis.

Arm/Group Title	Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)
Arm/Group Description:	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate 37.5mg PO QD for 4 weeks and placebo sorafenib tosylate 400mg PO QD or BID for 6 weeks.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate 400mg PO QD or BID for 6 weeks and placebo sunitinib malate 37.5mg PO QD for 4 weeks followed.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate 400mg as in Arm A and placebo sunitinib malate 37.5mg as in Arm B.
Overall Number of Participants Analyzed	542	540	540
Measure Type: Number; Number (97.5% Confidence Interval); Unit of Measure: proportion of participants
	0.534; (0.484 to 0.590)	0.527; (0.478 to 0.582)	0.560; (0.511 to 0.614)

5. Other Pre-specified Outcome

Title	The Association Between Angiogenesis Markers and Disease-free Survival
Description	[Not Specified]
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry

Outcome Measure Data Not Reported

6. Other Pre-specified Outcome

Title	The Association Between Disease-free Survival and the Frequency of Oncogene as Well as Tumor Suppressor Gene Mutations
Description	[Not Specified]
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry

Outcome Measure Data Not Reported

7. Other Pre-specified Outcome

Title	The Association Between Tumor and Genetic Polymorphisms and Disease-free Survival
Description	[Not Specified]
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry

Outcome Measure Data Not Reported

8. Other Pre-specified Outcome

Title	The Association Between Deoxyribonucleic Acid (DNA) Methylation Profiles and Disease-free Survival
Description	[Not Specified]
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry

Outcome Measure Data Not Reported

9. Other Pre-specified Outcome

Title	The Relationship of Polymorphisms in Drug Metabolizing Enzymes With Steady State Concentrations of Sorafenib and Sunitinib in Selected Patients
Description	[Not Specified]
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry

Outcome Measure Data Not Reported

10. Other Pre-specified Outcome

Title	The Effect of Vascular Endothelial Growth Factor (VEGF) Targeted Therapy on Circulating Endothelial Cells and Circulating Endothelial Progenitors
Description	[Not Specified]
Time Frame	Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; then annually if patient is 5 - 10 years from study entry

Outcome Measure Data Not Reported

11. Other Pre-specified Outcome

Title	Patient-reported Fatigue Using Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale
Description	[Not Specified]
Time Frame	Assessed at baseline, 10 weeks and 22 weeks

Outcome Measure Data Not Reported

12. Other Pre-specified Outcome

Title	Patient-reported Fatigue Using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form
Description	PROMIS Fatigue short form is a newly developed state-of-the-science PROMIS measure for fatigue
Time Frame	Assessed at baseline, 10 weeks and 22 weeks

Outcome Measure Data Not Reported

13. Other Pre-specified Outcome

Title	The Association Between Scan Frequency and Development of Congestive Heart Failure
Description	[Not Specified]
Time Frame	Assessed at 3, 6 and 12 months

Outcome Measure Data Not Reported

14. Other Pre-specified Outcome

Title	Frequency of Clinically Significant Congestive Heart Failure (CHF) Grade 3 or Higher Using the Common Terminology Criteria for Adverse Events Version 4.0
Description	[Not Specified]
Time Frame	Assessed every 6 weeks while on treatment and for 30 days after the end of treatment

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Assessed every 6 weeks while on treatment and for 30 days after the end of treatment
Adverse Event Reporting Description	Only adverse events that are possibly, probably, or definitely related to protocol therapy are reported.
Arm/Group Title	Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)
Arm/Group Description	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sunitinib malate 37.5mg PO QD for 4 weeks and placebo sorafenib tosylate 400mg PO QD or BID for 6 weeks.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive sorafenib tosylate 400mg PO QD or BID for 6 weeks and placebo sunitinib malate 37.5mg PO QD for 4 weeks followed.	Beginning 4-12 weeks following radical or partial nephrectomy, patients receive placebo sorafenib tosylate 400mg as in Arm A and placebo sunitinib malate 37.5mg as in Arm B.
All-Cause Mortality
	Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	368/625 (58.88%)	424/628 (67.52%)	81/626 (12.94%)
Blood and lymphatic system disorders
Anemia † 1	2/625 (0.32%)	1/628 (0.16%)	0/626 (0.00%)
Thrombotic microangiopathy † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Febrile neutropenia † 1	2/625 (0.32%)	0/628 (0.00%)	0/626 (0.00%)
Cardiac disorders
Heart block abnormality NOS † 1	0/625 (0.00%)	0/628 (0.00%)	1/626 (0.16%)
Atrial fibrillation † 1	1/625 (0.16%)	0/628 (0.00%)	2/626 (0.32%)
Atrial flutter † 1	0/625 (0.00%)	0/628 (0.00%)	2/626 (0.32%)
Sinus bradycardia † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Supraventricular tachycardia † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Bigeminy † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Cardiac-ischemia † 1	1/625 (0.16%)	3/628 (0.48%)	4/626 (0.64%)
Left ventricular systolic dysfunction † 1	4/625 (0.64%)	4/628 (0.64%)	2/626 (0.32%)
Cor Pulmonale † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
cardiac-other † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Cardiac/heart, pain † 1	2/625 (0.32%)	3/628 (0.48%)	0/626 (0.00%)
Ear and labyrinth disorders
Hearing w/o audiogr not in monitor prg † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Hyopthyroidism † 1	2/625 (0.32%)	0/628 (0.00%)	0/626 (0.00%)
Eye disorders
Cataract † 1	0/625 (0.00%)	0/628 (0.00%)	1/626 (0.16%)
Double vision † 1	0/625 (0.00%)	0/628 (0.00%)	1/626 (0.16%)
Retinal detachment † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Ocular-other † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Gastrointestinal disorders
Colitis † 1	0/625 (0.00%)	3/628 (0.48%)	0/626 (0.00%)
Constipation † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Diarrhea w/o prior colostomy † 1	57/625 (9.12%)	55/628 (8.76%)	2/626 (0.32%)
Distention/bloating, abdominal † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Esophagitis † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Gastritis † 1	1/625 (0.16%)	1/628 (0.16%)	0/626 (0.00%)
Dyspepsia † 1	14/625 (2.24%)	4/628 (0.64%)	1/626 (0.16%)
Ileus † 1	0/625 (0.00%)	0/628 (0.00%)	1/626 (0.16%)
Muco/stomatitis by exam, oral cavity † 1	2/625 (0.32%)	0/628 (0.00%)	0/626 (0.00%)
Muco/stomatitis (symptom) oral cavity † 1	3/625 (0.48%)	1/628 (0.16%)	0/626 (0.00%)
Nausea † 1	22/625 (3.52%)	5/628 (0.80%)	0/626 (0.00%)
Perforation, colon † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Vomiting † 1	11/625 (1.76%)	3/628 (0.48%)	1/626 (0.16%)
Colon, hemorrhage † 1	2/625 (0.32%)	0/628 (0.00%)	0/626 (0.00%)
Lower GI, hemorrhage NOS † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Stomach, hemorrhage † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Pancreatitis † 1	3/625 (0.48%)	1/628 (0.16%)	0/626 (0.00%)
Abdomen, pain † 1	4/625 (0.64%)	8/628 (1.27%)	2/626 (0.32%)
Esophagus, pain † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Oral cavity, pain † 1	1/625 (0.16%)	1/628 (0.16%)	0/626 (0.00%)
Stomach, pain † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
General disorders
Fatigue † 1	108/625 (17.28%)	41/628 (6.53%)	15/626 (2.40%)
Fever w/o neutropenia † 1	1/625 (0.16%)	2/628 (0.32%)	0/626 (0.00%)
Edema head and neck † 1	3/625 (0.48%)	1/628 (0.16%)	0/626 (0.00%)
Edema limb † 1	2/625 (0.32%)	0/628 (0.00%)	0/626 (0.00%)
Chest/thoracic pain NOS † 1	4/625 (0.64%)	4/628 (0.64%)	0/626 (0.00%)
Pain-other † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Flu-like syndrome † 1	3/625 (0.48%)	0/628 (0.00%)	0/626 (0.00%)
Hepatobiliary disorders
Cholecystitis † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Liver dysfunction/failure † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Hepatic-other † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Immune system disorders
Allergic reaction † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Infections and infestations
Infection w/ gr3-4 neut, ileum † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Infection Gr0-2 neut, appendix † 1	0/625 (0.00%)	0/628 (0.00%)	1/626 (0.16%)
Infection Gr0-2 neut, colon † 1	0/625 (0.00%)	2/628 (0.32%)	0/626 (0.00%)
Infection Gr0-2 neut, kidney † 1	1/625 (0.16%)	1/628 (0.16%)	0/626 (0.00%)
Infection Gr0-2 neut, lung † 1	2/625 (0.32%)	3/628 (0.48%)	2/626 (0.32%)
Infection Gr0-2 neut, mediastinm † 1	0/625 (0.00%)	0/628 (0.00%)	1/626 (0.16%)
Infection Gr0-2 neut, mucosa † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Infection Gr0-2 neut, muscle † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Infection Gr0-2 neut, nerve-cranial † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Infection Gr0-2 neut, skin † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Infection Gr0-2 neut, urinary tract † 1	1/625 (0.16%)	0/628 (0.00%)	1/626 (0.16%)
Infection Gr0-2 neut, vagina † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Infection Gr0-2 neut, wound † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Infection w/ unk ANC skin (cellulitis) † 1	0/625 (0.00%)	2/628 (0.32%)	0/626 (0.00%)
Infection w/ unk ANC urinary tract NOS † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Infection Gr0-2 neut, blood † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Infection-other † 1	1/625 (0.16%)	1/628 (0.16%)	0/626 (0.00%)
Injury, poisoning and procedural complications
Wound - non-infectious † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Vascular access,Thrombosis/embolism † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Investigations
Leukocytes decreased † 1	3/625 (0.48%)	0/628 (0.00%)	0/626 (0.00%)
Neutrophils decreased † 1	7/625 (1.12%)	2/628 (0.32%)	0/626 (0.00%)
Platelets decreased † 1	13/625 (2.08%)	2/628 (0.32%)	1/626 (0.16%)
Weight gain † 1	0/625 (0.00%)	0/628 (0.00%)	2/626 (0.32%)
Alanine aminotransferase increased † 1	4/625 (0.64%)	4/628 (0.64%)	0/626 (0.00%)
Serum amylase increased † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Aspartate aminotransferase increased † 1	6/625 (0.96%)	4/628 (0.64%)	0/626 (0.00%)
Blood bilirubin increased † 1	1/625 (0.16%)	1/628 (0.16%)	1/626 (0.16%)
Hypercholesterolemia † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
CPK increased † 1	1/625 (0.16%)	1/628 (0.16%)	0/626 (0.00%)
Creatinine increased † 1	1/625 (0.16%)	3/628 (0.48%)	0/626 (0.00%)
Lipase increased † 1	4/625 (0.64%)	3/628 (0.48%)	1/626 (0.16%)
Metabolism and nutrition disorders
Anorexia † 1	11/625 (1.76%)	5/628 (0.80%)	0/626 (0.00%)
Dehydration † 1	10/625 (1.60%)	3/628 (0.48%)	0/626 (0.00%)
Hypoalbuminemia † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Hypocalcemia † 1	1/625 (0.16%)	1/628 (0.16%)	0/626 (0.00%)
Hyperglycemia † 1	0/625 (0.00%)	1/628 (0.16%)	1/626 (0.16%)
Hypophosphatemia † 1	1/625 (0.16%)	1/628 (0.16%)	0/626 (0.00%)
Hyperkalemia † 1	3/625 (0.48%)	1/628 (0.16%)	0/626 (0.00%)
Hypokalemia † 1	2/625 (0.32%)	1/628 (0.16%)	0/626 (0.00%)
Hypernatremia † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Hyponatremia † 1	1/625 (0.16%)	5/628 (0.80%)	4/626 (0.64%)
Hypertriglyceridemia † 1	2/625 (0.32%)	0/628 (0.00%)	0/626 (0.00%)
Hyperuricemia † 1	0/625 (0.00%)	1/628 (0.16%)	3/626 (0.48%)
Musculoskeletal and connective tissue disorders
Nonneuropathic upper extr muscle weak † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Nonneuropathic left-side muscle weak † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Nonneuropathic right-side muscle weak † 1	0/625 (0.00%)	0/628 (0.00%)	1/626 (0.16%)
Nonneuropathic generalized weakness † 1	1/625 (0.16%)	1/628 (0.16%)	1/626 (0.16%)
Myositis † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Musculoskeletal/soft tissue-other † 1	0/625 (0.00%)	2/628 (0.32%)	0/626 (0.00%)
Back, pain † 1	1/625 (0.16%)	3/628 (0.48%)	0/626 (0.00%)
Bone, pain † 1	2/625 (0.32%)	1/628 (0.16%)	0/626 (0.00%)
Extremity-limb, pain † 1	4/625 (0.64%)	3/628 (0.48%)	0/626 (0.00%)
Joint, pain † 1	8/625 (1.28%)	8/628 (1.27%)	3/626 (0.48%)
Muscle, pain † 1	2/625 (0.32%)	8/628 (1.27%)	1/626 (0.16%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary malignancy † 1	0/625 (0.00%)	1/628 (0.16%)	1/626 (0.16%)
Nervous system disorders
Vasovagal episode † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Ataxia † 1	0/625 (0.00%)	0/628 (0.00%)	1/626 (0.16%)
CNS cerebrovascular ischemia † 1	4/625 (0.64%)	0/628 (0.00%)	1/626 (0.16%)
Cognitive disturbance † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Dizziness † 1	4/625 (0.64%)	2/628 (0.32%)	2/626 (0.32%)
Memory impairment † 1	1/625 (0.16%)	0/628 (0.00%)	1/626 (0.16%)
Neuropathy-motor † 1	3/625 (0.48%)	1/628 (0.16%)	0/626 (0.00%)
Neuropathy-sensory † 1	3/625 (0.48%)	12/628 (1.91%)	3/626 (0.48%)
Syncope † 1	4/625 (0.64%)	2/628 (0.32%)	0/626 (0.00%)
Head/headache † 1	6/625 (0.96%)	4/628 (0.64%)	0/626 (0.00%)
Psychiatric disorders
Insomnia † 1	0/625 (0.00%)	4/628 (0.64%)	0/626 (0.00%)
Confusion † 1	2/625 (0.32%)	0/628 (0.00%)	1/626 (0.16%)
Anxiety † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Depression † 1	1/625 (0.16%)	2/628 (0.32%)	2/626 (0.32%)
Renal and urinary disorders
Kidney, hemorrhage † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Proteinuria † 1	2/625 (0.32%)	2/628 (0.32%)	0/626 (0.00%)
Renal failure † 1	6/625 (0.96%)	4/628 (0.64%)	0/626 (0.00%)
Renal/GU-other † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Reproductive system and breast disorders
Sexual/Reproductive function-Other † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension † 1	0/625 (0.00%)	0/628 (0.00%)	1/626 (0.16%)
Muco/stomatitis (symptom) pharynx † 1	24/625 (3.84%)	14/628 (2.23%)	0/626 (0.00%)
Nose, hemorrhage † 1	3/625 (0.48%)	0/628 (0.00%)	0/626 (0.00%)
Dyspnea † 1	4/625 (0.64%)	4/628 (0.64%)	2/626 (0.32%)
Pleural effusion (non-malignant) † 1	1/625 (0.16%)	1/628 (0.16%)	0/626 (0.00%)
Voice changes/dysarthria † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Skin and subcutaneous tissue disorders
Dry skin † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Nail changes † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Pruritus/itching † 1	1/625 (0.16%)	11/628 (1.75%)	1/626 (0.16%)
Rash/desquamation † 1	15/625 (2.40%)	93/628 (14.81%)	3/626 (0.48%)
Rash: acne/acneiform † 1	0/625 (0.00%)	2/628 (0.32%)	0/626 (0.00%)
Erythema multiforme † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Hand-foot reaction † 1	94/625 (15.04%)	208/628 (33.12%)	7/626 (1.12%)
Urticaria † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Scalp, pain † 1	0/625 (0.00%)	2/628 (0.32%)	0/626 (0.00%)
Skin, pain † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
Vascular disorders
Hypertension † 1	104/625 (16.64%)	96/628 (15.29%)	15/626 (2.40%)
Hypotension † 1	1/625 (0.16%)	0/628 (0.00%)	0/626 (0.00%)
Thrombosis/thrombus/embolism † 1	3/625 (0.48%)	5/628 (0.80%)	1/626 (0.16%)
Vascular-Other (Specify) † 1	0/625 (0.00%)	1/628 (0.16%)	0/626 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE 3.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm A (Sunitinib + Sorafenib Placebo)	Arm B (Sorafenib + Sunitinib Placebo)	Arm C (Sunitinib Placebo + Sorafenib Placebo)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	116/625 (18.56%)	117/628 (18.63%)	57/626 (9.11%)
Gastrointestinal disorders
Diarrhea w/o prior colostomy † 1	41/625 (6.56%)	40/628 (6.37%)	13/626 (2.08%)
Nausea † 1	33/625 (5.28%)	21/628 (3.34%)	11/626 (1.76%)
General disorders
Fatigue † 1	62/625 (9.92%)	58/628 (9.24%)	31/626 (4.95%)
Skin and subcutaneous tissue disorders
Rash/desquamation † 1	17/625 (2.72%)	43/628 (6.85%)	15/626 (2.40%)
Hand-foot reaction † 1	36/625 (5.76%)	52/628 (8.28%)	7/626 (1.12%)
Vascular disorders
Hypertension † 1	38/625 (6.08%)	38/628 (6.05%)	10/626 (1.60%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE 3.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office
• Phone: 617-632-3012

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jamil ML, Keeley J, Sood A, Dalela D, Arora S, Peabody JO, Trinh QD, Menon M, Rogers CG, Abdollah F. Long-term Risk of Recurrence in Surgically Treated Renal Cell Carcinoma: A Post Hoc Analysis of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E2805 Trial Cohort. Eur Urol. 2020 Feb;77(2):277-281. doi: 10.1016/j.eururo.2019.10.028. Epub 2019 Nov 6.

Buti S, Puligandla M, Bersanelli M, DiPaola RS, Manola J, Taguchi S, Haas NB. Validation of a new prognostic model to easily predict outcome in renal cell carcinoma: the GRANT score applied to the ASSURE trial population. Ann Oncol. 2017 Nov 1;28(11):2747-2753. doi: 10.1093/annonc/mdx492. Erratum in: Ann Oncol. 2018 Jul 1;29(7):1604.

Haas NB, Manola J, Dutcher JP, Flaherty KT, Uzzo RG, Atkins MB, DiPaola RS, Choueiri TK. Adjuvant Treatment for High-Risk Clear Cell Renal Cancer: Updated Results of a High-Risk Subset of the ASSURE Randomized Trial. JAMA Oncol. 2017 Sep 1;3(9):1249-1252. doi: 10.1001/jamaoncol.2017.0076.

Haas NB, Manola J, Uzzo RG, Flaherty KT, Wood CG, Kane C, Jewett M, Dutcher JP, Atkins MB, Pins M, Wilding G, Cella D, Wagner L, Matin S, Kuzel TM, Sexton WJ, Wong YN, Choueiri TK, Pili R, Puzanov I, Kohli M, Stadler W, Carducci M, Coomes R, DiPaola RS. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016 May 14;387(10032):2008-16. doi: 10.1016/S0140-6736(16)00559-6. Epub 2016 Mar 9. Erratum in: Lancet. 2016 May 14;387(10032):1998.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00326898
• Other Study ID Numbers: NCI-2009-00534; NCI-2009-00534 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CAN-NCIC-E2805; SWOG-E2805; ECOG-E2805; CDR0000478976; CALGB-E2805; E2805 ( Other Identifier: ECOG-ACRIN Cancer Research Group ); E2805 ( Other Identifier: CTEP ); U10CA180820 ( U.S. NIH Grant/Contract ); U10CA021115 ( U.S. NIH Grant/Contract )
• First Submitted: May 16, 2006
• First Posted: May 17, 2006
• Results First Submitted: October 18, 2016
• Results First Posted: December 12, 2016
• Last Update Posted: July 7, 2020