Phase II Study of Afinitor vs. Sutent in Patients With Metastatic Non-Clear Cell Renal Cell Carcinoma (ASPEN)

• ClinicalTrials.gov Identifier: NCT01108445
• Recruitment Status: Completed
• First Posted: April 22, 2010
• Results First Posted: June 20, 2016
• Last Update Posted: January 16, 2018
• Sponsor: Duke University
• Collaborators: Novartis; Pfizer
• Information provided by (Responsible Party): Duke University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Non-clear Cell Renal Cell Carcinoma
• Interventions: Drug: Everolimus; Drug: Sunitinib
• Enrollment: 131

Participant Flow

Recruitment Details	131 participants signed consent. 22 were screen failures. 1 withdrew consent prior to being randomized. 108 participant were randomized.
Pre-assignment Details

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Period Title: Overall Study
Started	57	51
Completed	1	2
Not Completed	56	49

Baseline Characteristics

Arm/Group Title		RAD001	Sunitinib	Total
Arm/Group Description		Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.	Total of all reporting groups
Overall Number of Baseline Participants		57	51	108
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	57 participants	51 participants	108 participants
		61.9 (11.85)	60.9 (15.3)	61.4 (13.53)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	57 participants	51 participants	108 participants
	Female	13 22.8%	14 27.5%	27 25.0%
	Male	44 77.2%	37 72.5%	81 75.0%

Outcome Measures

1. Primary Outcome

Title	Anti-tumor Activity as Measured by Median Progression Free Survival Time
Description	The primary objective will be to compare the anti-tumor activity of everolimus and sunitinib in subjects with mRCC with non-clear cell pathology, as measured by progression-free survival (PFS) following treatment initiation according to RECIST 1.1 criteria. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Median (80% Confidence Interval); Unit of Measure: Months
	5.6; (5.5 to 6.0)	8.3; (5.8 to 11.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RAD001, Sunitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.157
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.406
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Progression Free Survival Rates
Description	6-, 12-, and 24-month rates of PFS in each arm will be compared for each treatment arm. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time Frame	6, 12 and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
6 Months	40.3; (27.3 to 52.8)	55.0; (40.1 to 67.7)
12 Months	17.0; (8.4 to 28.3)	37.7; (24.1 to 51.2)
24 Months	9.3; (3.0 to 20.2)	22.8; (11.7 to 36.1)

3. Secondary Outcome

Title	PFS Expressed in Months
Description	Progression-free survival (PFS) expressed in months as compared to an historic control (interferon-treated clear cell RCC control arm from the sunitinib phase III study). Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Median (95% Confidence Interval); Unit of Measure: Months
	5.6; (4.4 to 6.1)	8.3; (5.6 to 13.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RAD001
	Comments	A comparison of the median PFS for RAD001 arm was compared to the 95% confidence interval(CI) of the median PFS of the historical control (HC). The null hypothesis was that there is no difference in the median PFS between the treatment arms and the historical control. If the median PFS is outside the 95%CI for the HC,it is determined there is statistical evidence that median PFS is different from the HC.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median PFS
	Estimated Value	5.6
	Estimation Comments	The 95% CI for the HC was (4,6). If the median PFS for RAD001 is within the 95% CI for the HC, it is determined that there is not enough statistical evidence to say that the median PFS is different than the HC.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sunitinib
	Comments	A comparison of the median PFS for Sunitinib arm was compared to the 95% confidence interval(CI) of the median PFS of the historical control (HC). The null hypothesis was that there is no difference in the median PFS between the treatment arms and the historical control. If the median PFS is outside the 95%CI for the HC,it is determined there is statistical evidence that median PFS is different from the HC.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median PFS
	Estimated Value	8.3
	Estimation Comments	95% CI for HC was(4,6). If the median PFS for Sunitinib is within the 95% CI for the HC,it is determined that there is not enough statistical evidence to say that the median PFS is different than the HC.

4. Secondary Outcome

Title	Overall Response Rate
Description	Defined as complete response [CR] and partial response [PR] by RECIST 1.1 criteria in each treatment arm.Overall Response Rate (ORR) = CR + PR. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	8.8; (1.4 to 16.1)	17.6; (7.2 to 28.1)

5. Secondary Outcome

Title	Percentage of Participants With Stable Disease (SD)
Description	Percentage of participants with stable disease during treatment is defined as stable disease [SD] by RECIST 1.1 criteria as calculated in each treatment arm. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame	Baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	59.6; (46.9 to 72.4)	64.7; (51.6 to 77.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RAD001, Sunitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.589
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

6. Secondary Outcome

Title	12 Week Clinical Benefit Rate as Percentage
Description	Rate of complete or partial response or stable disease by the RECIST 1.1 criteria lasting ≥ 12 weeks prior to progression. Benefit rate is defined as complete response [CR] and partial response [PR] and stable disease [SD] by RECIST 1.1 criteria in each treatment arm. Benefit rate = CR + PR + SD. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame	Baseline to 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of particpants
	24.6; (13.4 to 35.7)	41.2; (27.7 to 54.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RAD001, Sunitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.066
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

7. Secondary Outcome

Title	Overall Survival Rates
Description	To compare overall survival (OS) rates at 6, 12, 24, and 36 months and over time in each treatment arm.
Time Frame	6, 12, 24, 36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage probability
6 months	83.5; (70.7 to 91.1)	85.4; (71.8 to 92.8)
12 months	57.7; (43.0 to 69.8)	74.7; (59.7 to 84.8)
24 months	40.8; (26.4 to 54.6)	51.3; (35.1 to 65.3)
36 months	35.7; (20.6 to 51.0)	46.2; (29.0 to 61.7)

8. Secondary Outcome

Title	Best Tumor Shrinkage as a Percentile in Each Arm
Description	To compare the best tumor shrinkage as a percentile in each treatment arm. The percentile change at each follow up visit is calculated by measuring the percentage change in the Sum of lesion measurement from baseline. The best tumor shrinkage is lowest percentile change. A decrease is indicated by a negative percentage.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Median (Inter-Quartile Range); Unit of Measure: percentile decrease
	-2.1; (-14.5 to 5.8)	-10.7; (-24.1 to 7.1)

9. Secondary Outcome

Title	Median Duration of Response (CR, PR, and SD)
Description	To compare the median duration of response (CR, PR, and SD) in each treatment arm. According to RECIST 1.1, Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Median (Inter-Quartile Range); Unit of Measure: months
	3.9; (2.8 to 9.1)	8.3; (3.1 to 17.2)

10. Secondary Outcome

Title	Median OS
Description	To compare the median OS in each treatment arm.
Time Frame	Up to 40 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Median (95% Confidence Interval); Unit of Measure: months
	13.2; (9.7 to 37.9)	31.5 [1]; (14.8 to NA)

[1]

The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

11. Secondary Outcome

Title	Time-to-new Metastatic Disease in Each Treatment Arm
Description	To compare the time-to-new metastatic disease in each treatment arm, defined from the date of first study agent administration to the onset of a new evaluable site of disease, excluding the primary site and all sites documented at baseline
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Median (95% Confidence Interval); Unit of Measure: months
	19.4; (8.2 to 36)	36; (11.4 to 36)

12. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	To assess toxicities associated with everolimus or sunitinib using NCI CTC version 4.0 criteria
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	57	51
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	63.2; (50.6 to 75.7)	80.4; (69.5 to 91.3)

13. Secondary Outcome

Title	Change in Quality-of-life
Description	To compare change in quality-of-life, as measured by the FACT-KSI scale at baseline and cycle 3 day 1 per subject in each treatment arm. Functional Assessment of Cancer Therapy Kidney Symptom Index. FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.
Time Frame	baseline, cycle 3 day 1

Outcome Measure Data

Analysis Population Description

All participants who completed the cycle 3 day 1 visit.

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	30	31
Mean (Standard Deviation); Unit of Measure: units on a scale
	-3.5 (9.61)	-0.9 (7.19)

14. Secondary Outcome

Title	Change in Quality-of-life
Description	To compare change in quality-of-life, as measured by the FACT-KSI scale at baseline and cycle 6 day1 per subject in each treatment arm. Functional Assessment of Cancer Therapy Kidney Symptom Index. FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.
Time Frame	baseline, cycle 6 day 1

Outcome Measure Data

Analysis Population Description

All participants who completed the cycle 6 day 1 visit.

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	13	17
Mean (Standard Deviation); Unit of Measure: units on a scale
	-4.4 (6.37)	-2.1 (6.69)

15. Secondary Outcome

Title	Change in Quality-of-life
Description	To compare change in quality-of-life, as measured by the FACT-KSI scale at baseline and end of treatment per subject in each treatment arm. Functional Assessment of Cancer Therapy Kidney Symptom Index. FKSI is a questionnaire for FACT-Kidney Symptom Index used to assess QoL/participant-reported outcomes for participants diagnosed with renal cell cancer. The FKSI contained 15 questions each ranging from 0 (not at all) to 4 (very much) so that FKSI ranged between 0-60 where higher scores reflects better functioning and fewer symptoms.
Time Frame	baseline, up to 40 months

Outcome Measure Data

Analysis Population Description

All participants who completed the End of treatment visit.

Arm/Group Title	RAD001	Sunitinib
Arm/Group Description:	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
Overall Number of Participants Analyzed	32	30
Mean (Standard Deviation); Unit of Measure: units on a scale
	-6.6 (7.83)	-6.4 (10.04)

16. Other Pre-specified Outcome

Title	Clinical Measures of Response and PFS With Baseline and Time-dependent Levels of Biomarkers
Description	To correlate clinical measures of response and PFS with baseline and time-dependent levels of biomarkers. These biomarkers include plasma angiokine levels, tissue immunohistochemical and genomic profiles, copy number as assessed by array-based comparative genomic hybridization (CGH), and known mutations in non-clear cell RCC
Time Frame	36 months

Outcome Measure Data Not Reported

17. Other Pre-specified Outcome

Title	Changes in Copy Number, RNA Expression, and Immunohistochemical Profiles
Description	To evaluate in an exploratory fashion changes in copy number, RNA expression, and immunohistochemical profiles by microarray between primary non-clear cell RCC tumors and metastatic samples
Time Frame	36 months

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Baseline to 40 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	RAD001	Sunitinib
Arm/Group Description	Subjects in this treatment arm will receive everolimus/RAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle. Everolimus: Subjects in this treatment arm will receive everolimusRAD001 10 mg orally once daily by mouth on days 1 through 42 for each 42 day cycle.	Subjects in this treatment arm will take sunitinib 50 mg daily by mouth on days 1 through 28 of each 42 day cycle. Sunitinib: 50 mg daily by mouth on days 1 through 28 of each 42 day cycle.
All-Cause Mortality
	RAD001	Sunitinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	RAD001	Sunitinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	36/57 (63.16%)	41/51 (80.39%)
Cardiac disorders
Cardiac failure congestive	0/57 (0.00%)	1/51 (1.96%)
Myocardial infarction	0/57 (0.00%)	1/51 (1.96%)
Gastrointestinal disorders
Abdominal pain	2/57 (3.51%)	1/51 (1.96%)
Abdominal pain upper	1/57 (1.75%)	0/51 (0.00%)
Ascites	2/57 (3.51%)	2/51 (3.92%)
Diarrhoea	2/57 (3.51%)	0/51 (0.00%)
Nausea	1/57 (1.75%)	1/51 (1.96%)
Small intestinal obstruction	2/57 (3.51%)	0/51 (0.00%)
Vomiting	1/57 (1.75%)	3/51 (5.88%)
Pancreatitis	0/57 (0.00%)	1/51 (1.96%)
General disorders
Disease progression	2/57 (3.51%)	1/51 (1.96%)
Mucosal inflammation	1/57 (1.75%)	0/51 (0.00%)
Multi-organ failure	1/57 (1.75%)	0/51 (0.00%)
Pain	1/57 (1.75%)	0/51 (0.00%)
Pyrexia	1/57 (1.75%)	0/51 (0.00%)
Hepatobiliary disorders
Cholecystitis	0/57 (0.00%)	1/51 (1.96%)
Infections and infestations
Clostridium difficile colitis	1/57 (1.75%)	0/51 (0.00%)
Gastroenteritis	1/57 (1.75%)	0/51 (0.00%)
Lung infection	1/57 (1.75%)	0/51 (0.00%)
Pneumonia	1/57 (1.75%)	1/51 (1.96%)
Anal abscess	0/57 (0.00%)	1/51 (1.96%)
Urinary tract infection	0/57 (0.00%)	1/51 (1.96%)
Injury, poisoning and procedural complications
Hip fracture	0/57 (0.00%)	1/51 (1.96%)
Humerus fracture	0/57 (0.00%)	1/51 (1.96%)
Subdural haematoma	0/57 (0.00%)	1/51 (1.96%)
Investigations
Haemoglobin decreased	1/57 (1.75%)	0/51 (0.00%)
Metabolism and nutrition disorders
Dehydration	2/57 (3.51%)	1/51 (1.96%)
Musculoskeletal and connective tissue disorders
Back pain	0/57 (0.00%)	1/51 (1.96%)
Pain in extremity	0/57 (0.00%)	1/51 (1.96%)
Nervous system disorders
Haemorrhage intracranial	1/57 (1.75%)	0/51 (0.00%)
Haemorrhagic stroke	1/57 (1.75%)	0/51 (0.00%)
Spinal cord compression	1/57 (1.75%)	0/51 (0.00%)
Paraesthesia	0/57 (0.00%)	1/51 (1.96%)
Psychiatric disorders
Confusional state	1/57 (1.75%)	1/51 (1.96%)
Delirium	0/57 (0.00%)	1/51 (1.96%)
Mental status changes	0/57 (0.00%)	1/51 (1.96%)
Renal and urinary disorders
Nephropathy toxic	1/57 (1.75%)	0/51 (0.00%)
Renal failure acute	2/57 (3.51%)	2/51 (3.92%)
Renal impairment	1/57 (1.75%)	0/51 (0.00%)
Urinary retention	0/57 (0.00%)	1/51 (1.96%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/57 (5.26%)	2/51 (3.92%)
Epistaxis	0/57 (0.00%)	2/51 (3.92%)
Haemoptysis	0/57 (0.00%)	1/51 (1.96%)
Obstructive airways disorder	0/57 (0.00%)	1/51 (1.96%)
Pleuritic pain	0/57 (0.00%)	1/51 (1.96%)
Pulmonary embolism	0/57 (0.00%)	3/51 (5.88%)
Pneumonitis	5/57 (8.77%)	0/51 (0.00%)
Vascular disorders
Deep vein thrombosis	0/57 (0.00%)	1/51 (1.96%)
Embolism arterial	0/57 (0.00%)	1/51 (1.96%)
Hypertension	0/57 (0.00%)	2/51 (3.92%)
Embolism venous	1/57 (1.75%)	0/51 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	RAD001	Sunitinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	57/57 (100.00%)	51/51 (100.00%)
Blood and lymphatic system disorders
Anaemia	16/57 (28.07%)	14/51 (27.45%)
Leukopenia	2/57 (3.51%)	4/51 (7.84%)
Lymphadenopathy	1/57 (1.75%)	0/51 (0.00%)
Lymphopenia	1/57 (1.75%)	0/51 (0.00%)
Neutropenia	1/57 (1.75%)	5/51 (9.80%)
Thrombocytopenia	7/57 (12.28%)	12/51 (23.53%)
Normochromic normocytic anaemia	0/57 (0.00%)	1/51 (1.96%)
Cardiac disorders
Palpitations	1/57 (1.75%)	0/51 (0.00%)
Tachycardia	1/57 (1.75%)	0/51 (0.00%)
Bradycardia	0/57 (0.00%)	1/51 (1.96%)
Cardiac flutter	0/57 (0.00%)	1/51 (1.96%)
Left ventricular hypertrophy	0/57 (0.00%)	1/51 (1.96%)
Ear and labyrinth disorders
Ear disorder	1/57 (1.75%)	0/51 (0.00%)
Ear pain	2/57 (3.51%)	0/51 (0.00%)
Ear pruritus	1/57 (1.75%)	0/51 (0.00%)
Otorrhoea	1/57 (1.75%)	0/51 (0.00%)
Tinnitus	0/57 (0.00%)	1/51 (1.96%)
Endocrine disorders
Hyperthyroidism	0/57 (0.00%)	1/51 (1.96%)
Hypothyroidism	0/57 (0.00%)	3/51 (5.88%)
Eye disorders
Cataract	1/57 (1.75%)	0/51 (0.00%)
Conjunctivitis	1/57 (1.75%)	0/51 (0.00%)
Dry eye	2/57 (3.51%)	2/51 (3.92%)
Eye discharge	1/57 (1.75%)	0/51 (0.00%)
Eye irritation	1/57 (1.75%)	0/51 (0.00%)
Eye pain	1/57 (1.75%)	0/51 (0.00%)
Periorbital oedema	2/57 (3.51%)	2/51 (3.92%)
Vision blurred	2/57 (3.51%)	0/51 (0.00%)
Conjunctival hyperaemia	0/57 (0.00%)	1/51 (1.96%)
Conjunctival oedema	0/57 (0.00%)	1/51 (1.96%)
Conjunctival pallor	0/57 (0.00%)	1/51 (1.96%)
Eye swelling	0/57 (0.00%)	1/51 (1.96%)
Eyelid oedema	0/57 (0.00%)	1/51 (1.96%)
Glaucoma	0/57 (0.00%)	1/51 (1.96%)
Lacrimation increased	0/57 (0.00%)	3/51 (5.88%)
Photopsia	0/57 (0.00%)	1/51 (1.96%)
Vitreous floaters	0/57 (0.00%)	1/51 (1.96%)
Gastrointestinal disorders
Abdominal distension	2/57 (3.51%)	3/51 (5.88%)
Abdominal pain	7/57 (12.28%)	7/51 (13.73%)
Abdominal pain lower	1/57 (1.75%)	2/51 (3.92%)
Abdominal pain upper	3/57 (5.26%)	5/51 (9.80%)
Ascites	1/57 (1.75%)	1/51 (1.96%)
Cheilitis	4/57 (7.02%)	0/51 (0.00%)
Constipation	10/57 (17.54%)	15/51 (29.41%)
Diarrhoea	15/57 (26.32%)	34/51 (66.67%)
Dry mouth	4/57 (7.02%)	5/51 (9.80%)
Dyspepsia	5/57 (8.77%)	11/51 (21.57%)
Dysphagia	1/57 (1.75%)	1/51 (1.96%)
Faeces discoloured	1/57 (1.75%)	1/51 (1.96%)
Flatulence	1/57 (1.75%)	6/51 (11.76%)
Gastrooesophageal reflux disease	1/57 (1.75%)	8/51 (15.69%)
Gingival pain	1/57 (1.75%)	1/51 (1.96%)
Inguinal hernia	1/57 (1.75%)	0/51 (0.00%)
Lip swelling	1/57 (1.75%)	0/51 (0.00%)
Mouth ulceration	5/57 (8.77%)	1/51 (1.96%)
Nausea	26/57 (45.61%)	36/51 (70.59%)
Oral pain	2/57 (3.51%)	4/51 (7.84%)
Small intestinal obstruction	1/57 (1.75%)	0/51 (0.00%)
Stomatitis	27/57 (47.37%)	14/51 (27.45%)
Tongue blistering	1/57 (1.75%)	0/51 (0.00%)
Vomiting	13/57 (22.81%)	17/51 (33.33%)
Abdominal discomfort	0/57 (0.00%)	1/51 (1.96%)
Anal inflammation	0/57 (0.00%)	1/51 (1.96%)
Dental caries	0/57 (0.00%)	1/51 (1.96%)
Gingival bleeding	0/57 (0.00%)	1/51 (1.96%)
Gingival hypertrophy	0/57 (0.00%)	1/51 (1.96%)
Glossodynia	0/57 (0.00%)	2/51 (3.92%)
Haematochezia	0/57 (0.00%)	1/51 (1.96%)
Haemorrhoids	0/57 (0.00%)	2/51 (3.92%)
Lip pain	0/57 (0.00%)	1/51 (1.96%)
Rectal haemorrhage	0/57 (0.00%)	3/51 (5.88%)
Reflux oesophagitis	0/57 (0.00%)	1/51 (1.96%)
Toothache	0/57 (0.00%)	1/51 (1.96%)
General disorders
Asthenia	1/57 (1.75%)	2/51 (3.92%)
Chest pain	2/57 (3.51%)	0/51 (0.00%)
Chills	4/57 (7.02%)	3/51 (5.88%)
Fatigue	33/57 (57.89%)	31/51 (60.78%)
Hernia	1/57 (1.75%)	0/51 (0.00%)
Influenza like illness	3/57 (5.26%)	2/51 (3.92%)
Irritability	1/57 (1.75%)	1/51 (1.96%)
Local swelling	1/57 (1.75%)	0/51 (0.00%)
Mucosal inflammation	13/57 (22.81%)	12/51 (23.53%)
Non-cardiac chest pain	3/57 (5.26%)	1/51 (1.96%)
Oedema	1/57 (1.75%)	1/51 (1.96%)
Oedema peripheral	15/57 (26.32%)	8/51 (15.69%)
Pain	4/57 (7.02%)	5/51 (9.80%)
Pyrexia	8/57 (14.04%)	4/51 (7.84%)
Chest discomfort	0/57 (0.00%)	1/51 (1.96%)
Early satiety	0/57 (0.00%)	1/51 (1.96%)
Impaired healing	0/57 (0.00%)	1/51 (1.96%)
Hepatobiliary disorders
Hepatotoxicity	0/57 (0.00%)	1/51 (1.96%)
Hyperbilirubinaemia	0/57 (0.00%)	1/51 (1.96%)
Immune system disorders
Drug hypersensitivity	0/57 (0.00%)	1/51 (1.96%)
Seasonal allergy	0/57 (0.00%)	1/51 (1.96%)
Infections and infestations
Blister infected	1/57 (1.75%)	0/51 (0.00%)
Cellulitis	1/57 (1.75%)	1/51 (1.96%)
Cystitis	1/57 (1.75%)	0/51 (0.00%)
Ear infection	4/57 (7.02%)	1/51 (1.96%)
Folliculitis	1/57 (1.75%)	2/51 (3.92%)
Furuncle	1/57 (1.75%)	1/51 (1.96%)
Hepatitis B	1/57 (1.75%)	0/51 (0.00%)
Infection	1/57 (1.75%)	0/51 (0.00%)
Influenza	1/57 (1.75%)	1/51 (1.96%)
Localised infection	1/57 (1.75%)	0/51 (0.00%)
Lower respiratory tract infection	2/57 (3.51%)	1/51 (1.96%)
Lung infection	1/57 (1.75%)	0/51 (0.00%)
Lymph gland infection	1/57 (1.75%)	0/51 (0.00%)
Nasopharyngitis	3/57 (5.26%)	0/51 (0.00%)
Paronychia	2/57 (3.51%)	1/51 (1.96%)
Pneumonia	1/57 (1.75%)	1/51 (1.96%)
Rash pustular	1/57 (1.75%)	1/51 (1.96%)
Respiratory tract infection	1/57 (1.75%)	1/51 (1.96%)
Rhinitis	1/57 (1.75%)	0/51 (0.00%)
Sinusitis	2/57 (3.51%)	1/51 (1.96%)
Soft tissue infection	1/57 (1.75%)	0/51 (0.00%)
Urinary tract infection	2/57 (3.51%)	4/51 (7.84%)
Candidiasis	0/57 (0.00%)	1/51 (1.96%)
Gastroenteritis viral	0/57 (0.00%)	1/51 (1.96%)
Hand-foot-and-mouth disease	0/57 (0.00%)	1/51 (1.96%)
Oral candidiasis	0/57 (0.00%)	1/51 (1.96%)
Peritonsillar abscess	0/57 (0.00%)	1/51 (1.96%)
Pharyngitis	0/57 (0.00%)	1/51 (1.96%)
Pyelonephritis	0/57 (0.00%)	1/51 (1.96%)
Skin infection	0/57 (0.00%)	3/51 (5.88%)
Tooth abscess	0/57 (0.00%)	2/51 (3.92%)
Tooth infection	0/57 (0.00%)	1/51 (1.96%)
Upper respiratory tract infection	0/57 (0.00%)	2/51 (3.92%)
Urosepsis	0/57 (0.00%)	1/51 (1.96%)
Viral infection	0/57 (0.00%)	1/51 (1.96%)
Injury, poisoning and procedural complications
Contusion	1/57 (1.75%)	3/51 (5.88%)
Procedural pain	2/57 (3.51%)	0/51 (0.00%)
Skin laceration	1/57 (1.75%)	0/51 (0.00%)
Heart injury	0/57 (0.00%)	1/51 (1.96%)
Joint sprain	0/57 (0.00%)	1/51 (1.96%)
Laceration	0/57 (0.00%)	1/51 (1.96%)
Post procedural swelling	0/57 (0.00%)	1/51 (1.96%)
Investigations
Alanine aminotransferase increased	2/57 (3.51%)	5/51 (9.80%)
Aspartate aminotransferase increased	7/57 (12.28%)	10/51 (19.61%)
Blood alkaline phosphatase increased	3/57 (5.26%)	3/51 (5.88%)
Blood cholesterol increased	7/57 (12.28%)	1/51 (1.96%)
Blood creatine increased	2/57 (3.51%)	0/51 (0.00%)
Blood creatinine increased	6/57 (10.53%)	9/51 (17.65%)
Blood glucose increased	1/57 (1.75%)	0/51 (0.00%)
Blood magnesium decreased	1/57 (1.75%)	0/51 (0.00%)
Blood phosphorus decreased	1/57 (1.75%)	0/51 (0.00%)
Blood potassium decreased	1/57 (1.75%)	1/51 (1.96%)
Blood triglycerides increased	3/57 (5.26%)	0/51 (0.00%)
Blood urea increased	1/57 (1.75%)	3/51 (5.88%)
Chest X-ray abnormal	1/57 (1.75%)	0/51 (0.00%)
Glomerular filtration rate decreased	1/57 (1.75%)	4/51 (7.84%)
Haemoglobin decreased	1/57 (1.75%)	1/51 (1.96%)
Liver function test abnormal	2/57 (3.51%)	2/51 (3.92%)
Low density lipoprotein increased	1/57 (1.75%)	0/51 (0.00%)
Platelet count decreased	3/57 (5.26%)	8/51 (15.69%)
Weight decreased	10/57 (17.54%)	7/51 (13.73%)
Weight increased	1/57 (1.75%)	1/51 (1.96%)
Activated partial thromboplastin time prolonged	0/57 (0.00%)	1/51 (1.96%)
Aspartate aminotransferase	0/57 (0.00%)	2/51 (3.92%)
Bacterial test positive	0/57 (0.00%)	1/51 (1.96%)
Blood albumin decreased	0/57 (0.00%)	1/51 (1.96%)
Blood bilirubin increased	0/57 (0.00%)	3/51 (5.88%)
Blood calcium decreased	0/57 (0.00%)	1/51 (1.96%)
Blood ketone body increased	0/57 (0.00%)	1/51 (1.96%)
Blood lactate dehydrogenase increased	0/57 (0.00%)	3/51 (5.88%)
Blood lactic acid increased	0/57 (0.00%)	1/51 (1.96%)
Blood pressure increased	0/57 (0.00%)	4/51 (7.84%)
Blood thyroid stimulating hormone increased	0/57 (0.00%)	1/51 (1.96%)
Clostridium test positive	0/57 (0.00%)	1/51 (1.96%)
Electrocardiogram QT prolonged	0/57 (0.00%)	1/51 (1.96%)
Haptoglobin decreased	0/57 (0.00%)	1/51 (1.96%)
Lipase increased	0/57 (0.00%)	2/51 (3.92%)
Lymphocyte count decreased	0/57 (0.00%)	1/51 (1.96%)
Mean cell haemoglobin increased	0/57 (0.00%)	1/51 (1.96%)
Neutrophil count decreased	0/57 (0.00%)	8/51 (15.69%)
Protein total decreased	0/57 (0.00%)	1/51 (1.96%)
Protein total increased	0/57 (0.00%)	1/51 (1.96%)
Transaminases increased	0/57 (0.00%)	1/51 (1.96%)
Urine output decreased	0/57 (0.00%)	1/51 (1.96%)
White blood cell count decreased	0/57 (0.00%)	8/51 (15.69%)
Metabolism and nutrition disorders
Decreased appetite	15/57 (26.32%)	30/51 (58.82%)
Dehydration	2/57 (3.51%)	4/51 (7.84%)
Diabetes mellitus	1/57 (1.75%)	0/51 (0.00%)
Failure to thrive	1/57 (1.75%)	0/51 (0.00%)
Gout	2/57 (3.51%)	1/51 (1.96%)
Hypercalcaemia	1/57 (1.75%)	1/51 (1.96%)
Hypercholesterolaemia	1/57 (1.75%)	0/51 (0.00%)
Hyperglycaemia	7/57 (12.28%)	4/51 (7.84%)
Hyperkalaemia	3/57 (5.26%)	4/51 (7.84%)
Hyperlipidaemia	1/57 (1.75%)	0/51 (0.00%)
Hypermagnesaemia	1/57 (1.75%)	2/51 (3.92%)
Hypertriglyceridaemia	8/57 (14.04%)	0/51 (0.00%)
Hypoalbuminaemia	2/57 (3.51%)	3/51 (5.88%)
Hypocalcaemia	1/57 (1.75%)	2/51 (3.92%)
Hypoglycaemia	1/57 (1.75%)	1/51 (1.96%)
Hypokalaemia	2/57 (3.51%)	2/51 (3.92%)
Hyponatraemia	5/57 (8.77%)	7/51 (13.73%)
Hypophosphataemia	3/57 (5.26%)	5/51 (9.80%)
Acidosis	0/57 (0.00%)	1/51 (1.96%)
Hyperammonaemia	0/57 (0.00%)	1/51 (1.96%)
Hyperamylasaemia	0/57 (0.00%)	1/51 (1.96%)
Hyperlipasaemia	0/57 (0.00%)	1/51 (1.96%)
Hypernatraemia	0/57 (0.00%)	1/51 (1.96%)
Hyperphosphataemia	0/57 (0.00%)	1/51 (1.96%)
Hyperuricaemia	0/57 (0.00%)	3/51 (5.88%)
Hypomagnesaemia	0/57 (0.00%)	5/51 (9.80%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/57 (12.28%)	12/51 (23.53%)
Back pain	6/57 (10.53%)	15/51 (29.41%)
Bone pain	3/57 (5.26%)	0/51 (0.00%)
Flank pain	5/57 (8.77%)	7/51 (13.73%)
Joint swelling	1/57 (1.75%)	2/51 (3.92%)
Muscle mass	1/57 (1.75%)	0/51 (0.00%)
Muscle spasms	2/57 (3.51%)	2/51 (3.92%)
Musculoskeletal chest pain	6/57 (10.53%)	2/51 (3.92%)
Musculoskeletal pain	4/57 (7.02%)	4/51 (7.84%)
Myalgia	2/57 (3.51%)	2/51 (3.92%)
Neck pain	1/57 (1.75%)	2/51 (3.92%)
Pain in extremity	5/57 (8.77%)	7/51 (13.73%)
Plantar fasciitis	1/57 (1.75%)	0/51 (0.00%)
Soft tissue disorder	1/57 (1.75%)	0/51 (0.00%)
Coccydynia	0/57 (0.00%)	1/51 (1.96%)
Groin pain	0/57 (0.00%)	1/51 (1.96%)
Joint effusion	0/57 (0.00%)	1/51 (1.96%)
Muscle swelling	0/57 (0.00%)	1/51 (1.96%)
Muscular weakness	0/57 (0.00%)	2/51 (3.92%)
Musculoskeletal discomfort	0/57 (0.00%)	1/51 (1.96%)
Pain in jaw	0/57 (0.00%)	1/51 (1.96%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	1/57 (1.75%)	1/51 (1.96%)
Metastases to spine	0/57 (0.00%)	1/51 (1.96%)
Skin papilloma	0/57 (0.00%)	1/51 (1.96%)
Nervous system disorders
Ageusia	1/57 (1.75%)	1/51 (1.96%)
Dizziness	3/57 (5.26%)	6/51 (11.76%)
Dysgeusia	18/57 (31.58%)	25/51 (49.02%)
Headache	6/57 (10.53%)	5/51 (9.80%)
Lethargy	9/57 (15.79%)	10/51 (19.61%)
Loss of consciousness	1/57 (1.75%)	0/51 (0.00%)
Migraine	1/57 (1.75%)	1/51 (1.96%)
Neuropathy peripheral	3/57 (5.26%)	3/51 (5.88%)
Paraesthesia	2/57 (3.51%)	1/51 (1.96%)
Peripheral motor neuropathy	1/57 (1.75%)	0/51 (0.00%)
Asterixis	0/57 (0.00%)	1/51 (1.96%)
Disturbance in attention	0/57 (0.00%)	1/51 (1.96%)
Dysarthria	0/57 (0.00%)	1/51 (1.96%)
Encephalomalacia	0/57 (0.00%)	1/51 (1.96%)
Hepatic encephalopathy	0/57 (0.00%)	1/51 (1.96%)
Hyperaesthesia	0/57 (0.00%)	1/51 (1.96%)
Neurotoxicity	0/57 (0.00%)	1/51 (1.96%)
Parosmia	0/57 (0.00%)	1/51 (1.96%)
Peripheral sensory neuropathy	0/57 (0.00%)	1/51 (1.96%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	0/57 (0.00%)	1/51 (1.96%)
Psychiatric disorders
Depressed mood	1/57 (1.75%)	1/51 (1.96%)
Depression	2/57 (3.51%)	3/51 (5.88%)
Insomnia	6/57 (10.53%)	3/51 (5.88%)
Mental status changes	1/57 (1.75%)	1/51 (1.96%)
Mood altered	1/57 (1.75%)	1/51 (1.96%)
Sleep disorder	2/57 (3.51%)	1/51 (1.96%)
Anxiety	0/57 (0.00%)	8/51 (15.69%)
Confusional state	0/57 (0.00%)	1/51 (1.96%)
Dysphoria	0/57 (0.00%)	1/51 (1.96%)
Emotional distress	0/57 (0.00%)	1/51 (1.96%)
Restlessness	0/57 (0.00%)	1/51 (1.96%)
Renal and urinary disorders
Bladder hypertrophy	1/57 (1.75%)	0/51 (0.00%)
Bladder spasm	1/57 (1.75%)	0/51 (0.00%)
Cystitis noninfective	1/57 (1.75%)	0/51 (0.00%)
Dysuria	2/57 (3.51%)	2/51 (3.92%)
Haematuria	3/57 (5.26%)	5/51 (9.80%)
Micturition urgency	2/57 (3.51%)	0/51 (0.00%)
Nocturia	2/57 (3.51%)	0/51 (0.00%)
Pollakiuria	6/57 (10.53%)	1/51 (1.96%)
Proteinuria	1/57 (1.75%)	1/51 (1.96%)
Renal failure acute	1/57 (1.75%)	3/51 (5.88%)
Urinary tract pain	2/57 (3.51%)	1/51 (1.96%)
Azotaemia	0/57 (0.00%)	1/51 (1.96%)
Chromaturia	0/57 (0.00%)	1/51 (1.96%)
Renal impairment	0/57 (0.00%)	1/51 (1.96%)
Renal tubular necrosis	0/57 (0.00%)	1/51 (1.96%)
Urinary incontinence	0/57 (0.00%)	1/51 (1.96%)
Urine flow decreased	0/57 (0.00%)	1/51 (1.96%)
Reproductive system and breast disorders
Oedema genital	1/57 (1.75%)	0/51 (0.00%)
Perineal pain	1/57 (1.75%)	0/51 (0.00%)
Scrotal swelling	1/57 (1.75%)	0/51 (0.00%)
Breast discomfort	0/57 (0.00%)	1/51 (1.96%)
Genital rash	0/57 (0.00%)	2/51 (3.92%)
Pruritus genital	0/57 (0.00%)	1/51 (1.96%)
Scrotal oedema	0/57 (0.00%)	1/51 (1.96%)
Vaginal haemorrhage	0/57 (0.00%)	1/51 (1.96%)
Respiratory, thoracic and mediastinal disorders
Cough	25/57 (43.86%)	8/51 (15.69%)
Dysphonia	1/57 (1.75%)	1/51 (1.96%)
Dyspnoea	21/57 (36.84%)	9/51 (17.65%)
Dyspnoea exertional	4/57 (7.02%)	2/51 (3.92%)
Epistaxis	11/57 (19.30%)	7/51 (13.73%)
Haemoptysis	1/57 (1.75%)	2/51 (3.92%)
Hiccups	1/57 (1.75%)	0/51 (0.00%)
Hypoxia	1/57 (1.75%)	1/51 (1.96%)
Laryngeal inflammation	1/57 (1.75%)	1/51 (1.96%)
Lung disorder	1/57 (1.75%)	0/51 (0.00%)
Nasal congestion	1/57 (1.75%)	2/51 (3.92%)
Oropharyngeal pain	5/57 (8.77%)	1/51 (1.96%)
Paranasal sinus hypersecretion	1/57 (1.75%)	0/51 (0.00%)
Pharyngeal erythema	1/57 (1.75%)	0/51 (0.00%)
Pharyngeal inflammation	1/57 (1.75%)	0/51 (0.00%)
Pneumonitis	5/57 (8.77%)	0/51 (0.00%)
Productive cough	3/57 (5.26%)	1/51 (1.96%)
Pulmonary embolism	2/57 (3.51%)	0/51 (0.00%)
Rhinitis allergic	1/57 (1.75%)	0/51 (0.00%)
Sinus congestion	1/57 (1.75%)	0/51 (0.00%)
Increased upper airway secretion	0/57 (0.00%)	1/51 (1.96%)
Nasal discomfort	0/57 (0.00%)	1/51 (1.96%)
Nasal dryness	0/57 (0.00%)	1/51 (1.96%)
Pleuritic pain	0/57 (0.00%)	1/51 (1.96%)
Pneumonia aspiration	0/57 (0.00%)	1/51 (1.96%)
Rales	0/57 (0.00%)	1/51 (1.96%)
Respiratory failure	0/57 (0.00%)	1/51 (1.96%)
Rhinalgia	0/57 (0.00%)	1/51 (1.96%)
Rhinorrhoea	0/57 (0.00%)	1/51 (1.96%)
Skin and subcutaneous tissue disorders
Alopecia	2/57 (3.51%)	4/51 (7.84%)
Dermal cyst	1/57 (1.75%)	0/51 (0.00%)
Dermatitis acneiform	1/57 (1.75%)	4/51 (7.84%)
Dermatitis bullous	1/57 (1.75%)	0/51 (0.00%)
Dry skin	11/57 (19.30%)	7/51 (13.73%)
Eczema	1/57 (1.75%)	0/51 (0.00%)
Erythema	3/57 (5.26%)	4/51 (7.84%)
Hair colour changes	1/57 (1.75%)	2/51 (3.92%)
Hair growth abnormal	1/57 (1.75%)	0/51 (0.00%)
Nail disorder	1/57 (1.75%)	0/51 (0.00%)
Onychoclasis	1/57 (1.75%)	0/51 (0.00%)
Pain of skin	1/57 (1.75%)	1/51 (1.96%)
Palmar-plantar erythrodysaesthesia syndrome	8/57 (14.04%)	21/51 (41.18%)
Petechiae	1/57 (1.75%)	0/51 (0.00%)
Pruritus	9/57 (15.79%)	7/51 (13.73%)
Pruritus generalised	1/57 (1.75%)	0/51 (0.00%)
Rash	18/57 (31.58%)	11/51 (21.57%)
Rash erythematous	1/57 (1.75%)	1/51 (1.96%)
Rash maculo-papular	6/57 (10.53%)	2/51 (3.92%)
Rash papular	1/57 (1.75%)	0/51 (0.00%)
Rash pruritic	1/57 (1.75%)	1/51 (1.96%)
Skin exfoliation	1/57 (1.75%)	0/51 (0.00%)
Skin hyperpigmentation	1/57 (1.75%)	0/51 (0.00%)
Skin lesion	1/57 (1.75%)	0/51 (0.00%)
Skin reaction	1/57 (1.75%)	2/51 (3.92%)
Skin toxicity	1/57 (1.75%)	0/51 (0.00%)
Urticaria	1/57 (1.75%)	0/51 (0.00%)
Cold sweat	0/57 (0.00%)	1/51 (1.96%)
Decubitus ulcer	0/57 (0.00%)	1/51 (1.96%)
Ecchymosis	0/57 (0.00%)	2/51 (3.92%)
Hyperhidrosis	0/57 (0.00%)	3/51 (5.88%)
Ingrowing nail	0/57 (0.00%)	1/51 (1.96%)
Night sweats	0/57 (0.00%)	3/51 (5.88%)
Pigmentation disorder	0/57 (0.00%)	1/51 (1.96%)
Plantar erythema	0/57 (0.00%)	1/51 (1.96%)
Purpura	0/57 (0.00%)	1/51 (1.96%)
Rash macular	0/57 (0.00%)	1/51 (1.96%)
Scab	0/57 (0.00%)	1/51 (1.96%)
Skin discolouration	0/57 (0.00%)	1/51 (1.96%)
Skin disorder	0/57 (0.00%)	2/51 (3.92%)
Skin ulcer	0/57 (0.00%)	1/51 (1.96%)
Swelling face	0/57 (0.00%)	1/51 (1.96%)
Yellow skin	0/57 (0.00%)	3/51 (5.88%)
Vascular disorders
Deep vein thrombosis	1/57 (1.75%)	1/51 (1.96%)
Flushing	3/57 (5.26%)	1/51 (1.96%)
Hot flush	2/57 (3.51%)	3/51 (5.88%)
Hypertension	6/57 (10.53%)	23/51 (45.10%)
Hypotension	1/57 (1.75%)	4/51 (7.84%)
Thrombophlebitis superficial	1/57 (1.75%)	0/51 (0.00%)

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: Dr. Andrew J Armstrong
• Organization: Duke University Medical Center
• Phone: 919-668-4615
• EMail: andrew.armstrong@duke.edu

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

Armstrong AJ, Halabi S, Eisen T, Broderick S, Stadler WM, Jones RJ, Garcia JA, Vaishampayan UN, Picus J, Hawkins RE, Hainsworth JD, Kollmannsberger CK, Logan TF, Puzanov I, Pickering LM, Ryan CW, Protheroe A, Lusk CM, Oberg S, George DJ. Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol. 2016 Mar;17(3):378-388. doi: 10.1016/S1470-2045(15)00515-X. Epub 2016 Jan 13.

Winquist E, Rodrigues G. Open clinical uro-oncology trials in Canada. Can J Urol. 2012 Dec;19(6):6587-91. No abstract available.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01108445
• Other Study ID Numbers: Pro00020714; CRAD001L2402T ( Other Identifier: Novartis )
• First Submitted: April 20, 2010
• First Posted: April 22, 2010
• Results First Submitted: February 16, 2016
• Results First Posted: June 20, 2016
• Last Update Posted: January 16, 2018