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Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma (RECORD-3)

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ClinicalTrials.gov Identifier: NCT00903175
Recruitment Status : Completed
First Posted : May 18, 2009
Results First Posted : June 28, 2016
Last Update Posted : November 8, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Renal Cell Carcinoma
Interventions Drug: everolimus
Drug: sunitinib
Enrollment 471
Recruitment Details 238 patients were randomized to everolimus as 1st line followed by 2nd line sunitinib. All patients in this group were treated. 233 patients were randomized to the sunitinib as 1st line followed by 2nd line everolimus. However 2 of the 233 patients were not treated in this group.
Pre-assignment Details The trial had a crossover design: first-line therapy until disease progression followed by second-line therapy until disease progression.Patients were randomized 1:1 to either everolimus-sunitinib or sunitinib-everolimus treatment sequence and were stratified by MSKCC risk criteria
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Period Title: Period 1 - First Line
Started 238 231
Completed 161 [1] 142 [1]
Not Completed 77 89
Reason Not Completed
Adverse Event             36             50
Abnormal lab value(s)             0             1
Abnormal test procedure result(s)             1             0
Protocol Violation             3             3
Withdrawal by Subject             8             12
Administrative problems             12             13
Death             17             10
[1]
Completed = Disease progression (completed 1L)
Period Title: Period 2 - Second Line
Started 128 [1] 116 [2]
Completed 79 [3] 80 [3]
Not Completed 49 36
Reason Not Completed
Missing             1             0
Adverse Event             16             20
Withdrawal by Subject             7             5
Lost to Follow-up             1             0
Administrative problems             19             9
Death             5             2
[1]
139 from everolimus 1L planned to enter 2L period and cross over to sunitinib but only 128 did.
[2]
130 from Sunitinib 1L planned to enter 2L period and cross over to everolimus but only 116 did.
[3]
Completed = Disease progression - (completed 2L)
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L Total
Hide Arm/Group Description everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment Total of all reporting groups
Overall Number of Baseline Participants 238 233 471
Hide Baseline Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients. Following the intent-to-treat principle, patients are analyzed according to the treatment sequence and stratum they were assigned to at randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 238 participants 233 participants 471 participants
61.36  (12.102) 60.84  (11.627) 61.10  (11.860)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 238 participants 233 participants 471 participants
Female 72 57 129
Male 166 176 342
1.Primary Outcome
Title Progression Free Survival First-Line (PFS 1-L)
Hide Description PFS_1L based on investigator assessment of radiology data by RECIST 1.0, was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause during or after first-line treatment with everolimus or sunitinib. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
7.85
(5.55 to 8.25)
10.71
(8.18 to 11.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Everolimus 1L/Sunitinib 2L, Sunitinib 1L/Everolimus 2L
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Primary objective was to assess the non-inferiority of everolimus as compared to Sunitinib in terms of PFS-1L & was based on Bayesian methodology. If the estimated HR for PFS-1L had a value ≤ 1.1, non-inferiority of everolimus to Sunitinib would be declared. Non-inferiority of everolimus compared with Sunitinib as a first-line therapy was not achieved. The estimated HR for PFS-1L was 1.43 which did not satisfy the protocol-defined non-inferiority margin of a HR ≤ 1.1.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.43
Confidence Interval (2-Sided) 95%
1.15 to 1.77
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression-free Survival Combined (PFS-C)
Hide Description PFS-C (1L and 2L study drugs combined) was a composite endpoint which combined both lines of study treatment. It was defined as the time from the date of randomization to the first of the following: date of death due to any cause, or date of the first radiologically documented progression disease during or after the second-line treatment period for patients with a radiologically documented progression disease in the first-line treatment period and who had crossed-over to second-line treatment no more than 6 weeks after progression.
Time Frame based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to about 56 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
21.68
(15.05 to 26.71)
22.18
(16.03 to 29.83)
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival was defined as the time from date of randomization to date of death due to any cause. The analysis of OS included all deaths in the FAS regardless of when they were observed.
Time Frame Every 2 months from randomization up to 3 years after last patient randomized
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
22.41
(18.60 to 33.28)
29.47
(22.83 to 33.05)
4.Secondary Outcome
Title Overall Response Rate (ORR) - First -Line (1-L)
Hide Description ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) and was based on investigator assessment of radiology data per RECIST. Participants with best overall response of ‘Unknown’ were treated as non-responders in the calculation of the ORR. Confirmed CR = at least two determinations of CR at least 4 weeks apart before progression. Confirmed PR = at least two determinations of PR or better at least 4 weeks apart before progression. CR required a disappearance of all target and non-target lesions. PR required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as a reference the baseline sum of the longest diameters. Radiological assessments : every 12 weeks until disease progression, the start of another antineoplastic therapy or for any other reason.
Time Frame based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response (CR) 1 3
Partial Response (PR) 18 59
Overall Response Rate (CR + PR) 19 62
5.Secondary Outcome
Title Duration of Response (DoR) - First-Line (1-L)
Hide Description Duration of overall response (CR or PR) applies only to patients whose Best Overall Response (BOR) was Complete Response (CR) or Partial Response (PR) during the first-line treatment period. The start date was the date of first documented response (CR or PR) during the first-line treatment and the end date was the date of the event defined as the first documented progression or death due to underlying cancer during or after the same treatment line.
Time Frame based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population corresponds to the patients included in the Full analysis set (i.e. randomized patients analyzed according to the treatment and stratum they were assigned to at randomization) and who achieved a best overall response of CR or PR during the first-line treatment period.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 19 62
Median (95% Confidence Interval)
Unit of Measure: Months
13.37 [1] 
(8.3 to NA)
17.25 [1] 
(11.4 to NA)
[1]
N/A = Data not estimable due to few number of patient at this time point
6.Secondary Outcome
Title Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First-line Drug
Hide Description The Functional Assessment of Cancer Therapy – Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) is a set of items to assess symptoms experienced by patients with advanced kidney cancer. These symptoms include fatigue, pain, weight loss, dyspnea, cough, fever and hematuria. Each item is scored on a 5-point scale (0 = not at all; 4 = very much). The FKSI-DRS total score ranges from 0 (most severe symptoms) to 36 (no symptoms). Definitive deterioration was defined as a decrease by at least 3 units compared to baseline, with no later increase above this threshold observed during the 1-L of treatment. A single measure reporting a decrease of at least 3 units was considered definitive only if it was the last one available for the patient.
Time Frame <=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
12.65
(7.9 to 19.4)
16.66 [1] 
(13.7 to NA)
[1]
N/A = Data not estimable due to few number of patient at this time point
7.Secondary Outcome
Title Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First and Second-line Drugs Combined
Hide Description The Functional Assessment of Cancer Therapy – Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) is a set of items to assess symptoms experienced by patients with advanced kidney cancer. These symptoms include fatigue, pain, weight loss, dyspnea, cough, fever and hematuria. Each item is scored on a 5-point scale (0 = not at all; 4 = very much). The FKSI-DRS total score ranges from 0 (most severe symptoms) to 36 (no symptoms). Definitive deterioration was defined as a decrease by at least 3 units compared to baseline, with no later increase above this threshold observed during the 1-L or 2-L treatment. A single measure reporting a decrease of at least 3 units was considered definitive only if it was the last one available for the patient.
Time Frame <=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
14.23
(12.0 to 19.4)
15.97
(13.7 to 20.4)
8.Secondary Outcome
Title Time to Definitive Deterioration of the Physical Functioning (PF) Scale of the EORTC QLQ-C30 - by First-Line (1L) Drug
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items. The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line of treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
Time Frame <=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
13.47
(7.9 to 20.6)
14.03
(12.1 to 17.7)
9.Secondary Outcome
Title Time to Definitive Deterioration of the Physical Functioning Scale of the EORTC QLQ-C30 - by First and Second-Line Drugs Combined
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items.The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line or second line treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
Time Frame <=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
12.25
(9.5 to 16.3)
14.03
(12.0 to 17.7)
10.Secondary Outcome
Title Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First-Line Drug
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items.The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line of treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
Time Frame <=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
7.92
(5.6 to 12.1)
12.25
(7.9 to 14.1)
11.Secondary Outcome
Title Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First and Second-Line Drugs Combined
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items. The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line or second line treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
Time Frame <=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
10.84
(7.5 to 13.8)
12.71
(10.5 to 14.8)
12.Secondary Outcome
Title Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First-Line Drug
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items.The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line of treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
Time Frame <=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Median (95% Confidence Interval)
Unit of Measure: Months
9.20
(6.2 to 12.6)
11.37
(9.3 to 13.4)
13.Secondary Outcome
Title Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First and Second-Line Drugs Combined
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items. The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line or second line treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
Time Frame <=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all randomized patients analyzed according to the treatment and stratum they were assigned to at randomization.
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description:
everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Overall Number of Participants Analyzed 238 233
Mean (95% Confidence Interval)
Unit of Measure: Months
11.56
(7.9 to 14.1)
13.34
(10.8 to 15.9)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Hide Arm/Group Description everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
All-Cause Mortality
Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Affected / at Risk (%) Affected / at Risk (%)
Total   139/238 (58.40%)   131/231 (56.71%) 
Blood and lymphatic system disorders     
Anaemia  1  16/238 (6.72%)  9/231 (3.90%) 
Coagulopathy  1  1/238 (0.42%)  0/231 (0.00%) 
Disseminated intravascular coagulation  1  0/238 (0.00%)  1/231 (0.43%) 
Febrile neutropenia  1  0/238 (0.00%)  1/231 (0.43%) 
Lymph node pain  1  0/238 (0.00%)  1/231 (0.43%) 
Lymphopenia  1  0/238 (0.00%)  1/231 (0.43%) 
Thrombocytopenia  1  2/238 (0.84%)  9/231 (3.90%) 
Cardiac disorders     
Acute myocardial infarction  1  1/238 (0.42%)  2/231 (0.87%) 
Arrhythmia supraventricular  1  0/238 (0.00%)  1/231 (0.43%) 
Atrial fibrillation  1  7/238 (2.94%)  0/231 (0.00%) 
Atrial flutter  1  1/238 (0.42%)  0/231 (0.00%) 
Atrioventricular block second degree  1  1/238 (0.42%)  0/231 (0.00%) 
Bradycardia  1  0/238 (0.00%)  1/231 (0.43%) 
Cardiac arrest  1  1/238 (0.42%)  0/231 (0.00%) 
Cardiac failure  1  0/238 (0.00%)  2/231 (0.87%) 
Cardiac failure congestive  1  3/238 (1.26%)  0/231 (0.00%) 
Cardio-respiratory arrest  1  2/238 (0.84%)  0/231 (0.00%) 
Cardiomyopathy  1  0/238 (0.00%)  1/231 (0.43%) 
Cardiopulmonary failure  1  0/238 (0.00%)  2/231 (0.87%) 
Myocardial infarction  1  3/238 (1.26%)  3/231 (1.30%) 
Myocardial ischaemia  1  1/238 (0.42%)  1/231 (0.43%) 
Pericardial effusion  1  2/238 (0.84%)  0/231 (0.00%) 
Sinus bradycardia  1  0/238 (0.00%)  1/231 (0.43%) 
Sinus tachycardia  1  0/238 (0.00%)  1/231 (0.43%) 
Stress cardiomyopathy  1  1/238 (0.42%)  0/231 (0.00%) 
Supraventricular tachycardia  1  1/238 (0.42%)  0/231 (0.00%) 
Ventricular dysfunction  1  1/238 (0.42%)  0/231 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  0/238 (0.00%)  1/231 (0.43%) 
Endocrine disorders     
Hypothyroidism  1  0/238 (0.00%)  2/231 (0.87%) 
Eye disorders     
Corneal disorder  1  0/238 (0.00%)  1/231 (0.43%) 
Diplopia  1  0/238 (0.00%)  1/231 (0.43%) 
Optic ischaemic neuropathy  1  1/238 (0.42%)  0/231 (0.00%) 
Visual impairment  1  0/238 (0.00%)  1/231 (0.43%) 
Gastrointestinal disorders     
Abdominal distension  1  2/238 (0.84%)  1/231 (0.43%) 
Abdominal pain  1  6/238 (2.52%)  8/231 (3.46%) 
Abdominal pain lower  1  0/238 (0.00%)  1/231 (0.43%) 
Abdominal pain upper  1  3/238 (1.26%)  1/231 (0.43%) 
Anal fissure  1  2/238 (0.84%)  0/231 (0.00%) 
Anal fistula  1  1/238 (0.42%)  1/231 (0.43%) 
Ascites  1  2/238 (0.84%)  2/231 (0.87%) 
Colitis  1  1/238 (0.42%)  3/231 (1.30%) 
Constipation  1  1/238 (0.42%)  3/231 (1.30%) 
Diarrhoea  1  6/238 (2.52%)  5/231 (2.16%) 
Diverticulum  1  1/238 (0.42%)  0/231 (0.00%) 
Duodenal obstruction  1  1/238 (0.42%)  0/231 (0.00%) 
Dyspepsia  1  0/238 (0.00%)  1/231 (0.43%) 
Dysphagia  1  0/238 (0.00%)  1/231 (0.43%) 
Enteritis  1  1/238 (0.42%)  0/231 (0.00%) 
Enterocolitis  1  1/238 (0.42%)  0/231 (0.00%) 
Gastritis  1  1/238 (0.42%)  0/231 (0.00%) 
Gastrointestinal erosion  1  1/238 (0.42%)  0/231 (0.00%) 
Gastrointestinal haemorrhage  1  3/238 (1.26%)  2/231 (0.87%) 
Gastrointestinal inflammation  1  0/238 (0.00%)  1/231 (0.43%) 
Gingival bleeding  1  1/238 (0.42%)  0/231 (0.00%) 
Haematemesis  1  1/238 (0.42%)  1/231 (0.43%) 
Haematochezia  1  3/238 (1.26%)  0/231 (0.00%) 
Haemorrhoids  1  0/238 (0.00%)  1/231 (0.43%) 
Ileus  1  0/238 (0.00%)  1/231 (0.43%) 
Intestinal ischaemia  1  0/238 (0.00%)  1/231 (0.43%) 
Intestinal obstruction  1  3/238 (1.26%)  0/231 (0.00%) 
Localised intraabdominal fluid collection  1  0/238 (0.00%)  1/231 (0.43%) 
Melaena  1  1/238 (0.42%)  1/231 (0.43%) 
Nausea  1  4/238 (1.68%)  5/231 (2.16%) 
Oesophageal ulcer  1  0/238 (0.00%)  1/231 (0.43%) 
Oral pain  1  1/238 (0.42%)  0/231 (0.00%) 
Pancreatitis  1  3/238 (1.26%)  0/231 (0.00%) 
Peritoneal adhesions  1  1/238 (0.42%)  0/231 (0.00%) 
Rectal haemorrhage  1  1/238 (0.42%)  1/231 (0.43%) 
Small intestinal obstruction  1  0/238 (0.00%)  1/231 (0.43%) 
Stomatitis  1  6/238 (2.52%)  0/231 (0.00%) 
Upper gastrointestinal haemorrhage  1  1/238 (0.42%)  0/231 (0.00%) 
Vomiting  1  5/238 (2.10%)  8/231 (3.46%) 
General disorders     
Asthenia  1  6/238 (2.52%)  6/231 (2.60%) 
Fatigue  1  6/238 (2.52%)  5/231 (2.16%) 
General physical health deterioration  1  3/238 (1.26%)  4/231 (1.73%) 
Generalised oedema  1  1/238 (0.42%)  0/231 (0.00%) 
Impaired healing  1  1/238 (0.42%)  1/231 (0.43%) 
Influenza like illness  1  1/238 (0.42%)  1/231 (0.43%) 
Localised oedema  1  0/238 (0.00%)  1/231 (0.43%) 
Malaise  1  3/238 (1.26%)  1/231 (0.43%) 
Mucous membrane disorder  1  1/238 (0.42%)  0/231 (0.00%) 
Multi-organ failure  1  1/238 (0.42%)  1/231 (0.43%) 
Non-cardiac chest pain  1  2/238 (0.84%)  3/231 (1.30%) 
Oedema peripheral  1  2/238 (0.84%)  3/231 (1.30%) 
Pelvic mass  1  0/238 (0.00%)  1/231 (0.43%) 
Performance status decreased  1  1/238 (0.42%)  1/231 (0.43%) 
Peripheral swelling  1  1/238 (0.42%)  2/231 (0.87%) 
Pyrexia  1  10/238 (4.20%)  7/231 (3.03%) 
Sudden death  1  0/238 (0.00%)  1/231 (0.43%) 
Hepatobiliary disorders     
Cholangitis  1  0/238 (0.00%)  1/231 (0.43%) 
Cholecystitis  1  2/238 (0.84%)  4/231 (1.73%) 
Cholecystitis acute  1  2/238 (0.84%)  0/231 (0.00%) 
Cholelithiasis  1  1/238 (0.42%)  1/231 (0.43%) 
Haemobilia  1  0/238 (0.00%)  1/231 (0.43%) 
Hepatic function abnormal  1  0/238 (0.00%)  1/231 (0.43%) 
Hepatic haemorrhage  1  0/238 (0.00%)  1/231 (0.43%) 
Hyperbilirubinaemia  1  0/238 (0.00%)  1/231 (0.43%) 
Jaundice  1  0/238 (0.00%)  1/231 (0.43%) 
Jaundice cholestatic  1  1/238 (0.42%)  1/231 (0.43%) 
Immune system disorders     
Drug hypersensitivity  1  1/238 (0.42%)  0/231 (0.00%) 
Hypersensitivity  1  1/238 (0.42%)  0/231 (0.00%) 
Infections and infestations     
Abdominal abscess  1  0/238 (0.00%)  1/231 (0.43%) 
Abscess oral  1  0/238 (0.00%)  1/231 (0.43%) 
Anal abscess  1  0/238 (0.00%)  1/231 (0.43%) 
Aspergillus infection  1  0/238 (0.00%)  1/231 (0.43%) 
Bacteraemia  1  0/238 (0.00%)  1/231 (0.43%) 
Bacterial prostatitis  1  0/238 (0.00%)  1/231 (0.43%) 
Bacterial sepsis  1  1/238 (0.42%)  0/231 (0.00%) 
Bronchitis  1  1/238 (0.42%)  1/231 (0.43%) 
Bronchopneumonia  1  1/238 (0.42%)  0/231 (0.00%) 
Cellulitis  1  3/238 (1.26%)  3/231 (1.30%) 
Clostridium difficile infection  1  1/238 (0.42%)  0/231 (0.00%) 
Diverticulitis  1  1/238 (0.42%)  2/231 (0.87%) 
Empyema  1  1/238 (0.42%)  0/231 (0.00%) 
Endocarditis  1  1/238 (0.42%)  1/231 (0.43%) 
Escherichia sepsis  1  1/238 (0.42%)  0/231 (0.00%) 
Gastrointestinal viral infection  1  0/238 (0.00%)  1/231 (0.43%) 
Hepatitis A  1  1/238 (0.42%)  0/231 (0.00%) 
Herpes zoster  1  1/238 (0.42%)  0/231 (0.00%) 
Infected bites  1  0/238 (0.00%)  1/231 (0.43%) 
Kidney infection  1  0/238 (0.00%)  1/231 (0.43%) 
Localised infection  1  0/238 (0.00%)  1/231 (0.43%) 
Lower respiratory tract infection  1  2/238 (0.84%)  0/231 (0.00%) 
Lung infection  1  2/238 (0.84%)  1/231 (0.43%) 
Pneumonia  1  18/238 (7.56%)  15/231 (6.49%) 
Respiratory tract infection  1  2/238 (0.84%)  0/231 (0.00%) 
Salmonella sepsis  1  0/238 (0.00%)  1/231 (0.43%) 
Sepsis  1  3/238 (1.26%)  4/231 (1.73%) 
Septic shock  1  4/238 (1.68%)  2/231 (0.87%) 
Urinary tract infection  1  3/238 (1.26%)  5/231 (2.16%) 
Wound infection  1  1/238 (0.42%)  0/231 (0.00%) 
Wound sepsis  1  0/238 (0.00%)  1/231 (0.43%) 
Injury, poisoning and procedural complications     
Femoral neck fracture  1  1/238 (0.42%)  0/231 (0.00%) 
Femur fracture  1  1/238 (0.42%)  2/231 (0.87%) 
Head injury  1  1/238 (0.42%)  0/231 (0.00%) 
Heat stroke  1  1/238 (0.42%)  0/231 (0.00%) 
Hip fracture  1  1/238 (0.42%)  0/231 (0.00%) 
Humerus fracture  1  3/238 (1.26%)  0/231 (0.00%) 
Pneumothorax traumatic  1  1/238 (0.42%)  0/231 (0.00%) 
Post procedural haematoma  1  0/238 (0.00%)  1/231 (0.43%) 
Post-traumatic pain  1  0/238 (0.00%)  1/231 (0.43%) 
Rib fracture  1  2/238 (0.84%)  0/231 (0.00%) 
Road traffic accident  1  0/238 (0.00%)  1/231 (0.43%) 
Scar  1  1/238 (0.42%)  0/231 (0.00%) 
Subdural haematoma  1  1/238 (0.42%)  1/231 (0.43%) 
Subdural haemorrhage  1  1/238 (0.42%)  0/231 (0.00%) 
Investigations     
Blood creatinine increased  1  3/238 (1.26%)  3/231 (1.30%) 
Body temperature increased  1  1/238 (0.42%)  0/231 (0.00%) 
C-reactive protein increased  1  1/238 (0.42%)  0/231 (0.00%) 
Creatinine renal clearance decreased  1  0/238 (0.00%)  1/231 (0.43%) 
Eastern cooperative oncology group performance status worsened  1  1/238 (0.42%)  0/231 (0.00%) 
Electrocardiogram T wave abnormal  1  0/238 (0.00%)  1/231 (0.43%) 
Gamma-glutamyltransferase increased  1  0/238 (0.00%)  1/231 (0.43%) 
Haemoglobin decreased  1  1/238 (0.42%)  2/231 (0.87%) 
Hepatic enzyme increased  1  0/238 (0.00%)  1/231 (0.43%) 
Troponin  1  0/238 (0.00%)  1/231 (0.43%) 
Troponin I increased  1  1/238 (0.42%)  0/231 (0.00%) 
Troponin increased  1  1/238 (0.42%)  0/231 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  3/238 (1.26%)  0/231 (0.00%) 
Dehydration  1  13/238 (5.46%)  6/231 (2.60%) 
Diabetes mellitus  1  1/238 (0.42%)  1/231 (0.43%) 
Electrolyte imbalance  1  1/238 (0.42%)  0/231 (0.00%) 
Failure to thrive  1  1/238 (0.42%)  1/231 (0.43%) 
Feeding disorder  1  1/238 (0.42%)  0/231 (0.00%) 
Food intolerance  1  1/238 (0.42%)  0/231 (0.00%) 
Gout  1  1/238 (0.42%)  0/231 (0.00%) 
Hypercalcaemia  1  2/238 (0.84%)  5/231 (2.16%) 
Hyperglycaemia  1  4/238 (1.68%)  5/231 (2.16%) 
Hyperkalaemia  1  1/238 (0.42%)  1/231 (0.43%) 
Hypoalbuminaemia  1  1/238 (0.42%)  1/231 (0.43%) 
Hypocalcaemia  1  1/238 (0.42%)  0/231 (0.00%) 
Hypoglycaemia  1  2/238 (0.84%)  1/231 (0.43%) 
Hypokalaemia  1  1/238 (0.42%)  1/231 (0.43%) 
Hypomagnesaemia  1  1/238 (0.42%)  0/231 (0.00%) 
Hyponatraemia  1  0/238 (0.00%)  1/231 (0.43%) 
Hypovolaemia  1  0/238 (0.00%)  1/231 (0.43%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/238 (0.42%)  2/231 (0.87%) 
Back pain  1  5/238 (2.10%)  3/231 (1.30%) 
Bone pain  1  2/238 (0.84%)  1/231 (0.43%) 
Flank pain  1  3/238 (1.26%)  0/231 (0.00%) 
Fracture pain  1  0/238 (0.00%)  1/231 (0.43%) 
Muscular weakness  1  0/238 (0.00%)  1/231 (0.43%) 
Musculoskeletal chest pain  1  1/238 (0.42%)  0/231 (0.00%) 
Myalgia  1  1/238 (0.42%)  0/231 (0.00%) 
Osteonecrosis of jaw  1  0/238 (0.00%)  1/231 (0.43%) 
Pain in extremity  1  0/238 (0.00%)  2/231 (0.87%) 
Pathological fracture  1  4/238 (1.68%)  3/231 (1.30%) 
Spinal column stenosis  1  1/238 (0.42%)  0/231 (0.00%) 
Spinal pain  1  0/238 (0.00%)  1/231 (0.43%) 
Vertebral lesion  1  0/238 (0.00%)  1/231 (0.43%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  0/238 (0.00%)  1/231 (0.43%) 
Endometrial adenocarcinoma  1  0/238 (0.00%)  1/231 (0.43%) 
Gastrointestinal stromal tumour  1  1/238 (0.42%)  0/231 (0.00%) 
Lung neoplasm malignant  1  1/238 (0.42%)  0/231 (0.00%) 
Lymphangiosis carcinomatosa  1  1/238 (0.42%)  0/231 (0.00%) 
Malignant ascites  1  1/238 (0.42%)  0/231 (0.00%) 
Malignant neoplasm progression  1  1/238 (0.42%)  0/231 (0.00%) 
Metastases to bone  1  2/238 (0.84%)  0/231 (0.00%) 
Metastases to central nervous system  1  1/238 (0.42%)  1/231 (0.43%) 
Renal cell carcinoma  1  0/238 (0.00%)  1/231 (0.43%) 
Squamous cell carcinoma  1  0/238 (0.00%)  1/231 (0.43%) 
Tumour associated fever  1  0/238 (0.00%)  1/231 (0.43%) 
Tumour pain  1  0/238 (0.00%)  1/231 (0.43%) 
Waldenstrom's macroglobulinaemia  1  1/238 (0.42%)  0/231 (0.00%) 
Nervous system disorders     
Balance disorder  1  0/238 (0.00%)  1/231 (0.43%) 
Brain oedema  1  0/238 (0.00%)  1/231 (0.43%) 
Cerebral haemorrhage  1  3/238 (1.26%)  1/231 (0.43%) 
Cerebrovascular accident  1  2/238 (0.84%)  1/231 (0.43%) 
Coma  1  0/238 (0.00%)  1/231 (0.43%) 
Dizziness  1  1/238 (0.42%)  1/231 (0.43%) 
Dysgeusia  1  1/238 (0.42%)  0/231 (0.00%) 
Generalised tonic-clonic seizure  1  0/238 (0.00%)  1/231 (0.43%) 
Haemorrhagic stroke  1  0/238 (0.00%)  1/231 (0.43%) 
Headache  1  2/238 (0.84%)  0/231 (0.00%) 
Hemiparesis  1  2/238 (0.84%)  0/231 (0.00%) 
Hypoaesthesia  1  0/238 (0.00%)  1/231 (0.43%) 
Intracranial pressure increased  1  0/238 (0.00%)  1/231 (0.43%) 
Lethargy  1  1/238 (0.42%)  0/231 (0.00%) 
Loss of consciousness  1  0/238 (0.00%)  2/231 (0.87%) 
Meningorrhagia  1  0/238 (0.00%)  1/231 (0.43%) 
Neuralgia  1  0/238 (0.00%)  1/231 (0.43%) 
Seizure  1  0/238 (0.00%)  2/231 (0.87%) 
Somnolence  1  0/238 (0.00%)  1/231 (0.43%) 
Spinal cord compression  1  4/238 (1.68%)  3/231 (1.30%) 
Status epilepticus  1  0/238 (0.00%)  1/231 (0.43%) 
Syncope  1  1/238 (0.42%)  2/231 (0.87%) 
Transient ischaemic attack  1  1/238 (0.42%)  1/231 (0.43%) 
Visual field defect  1  1/238 (0.42%)  0/231 (0.00%) 
Psychiatric disorders     
Anxiety  1  1/238 (0.42%)  0/231 (0.00%) 
Completed suicide  1  1/238 (0.42%)  0/231 (0.00%) 
Confusional state  1  1/238 (0.42%)  2/231 (0.87%) 
Disorientation  1  0/238 (0.00%)  1/231 (0.43%) 
Mental status changes  1  1/238 (0.42%)  0/231 (0.00%) 
Panic attack  1  1/238 (0.42%)  0/231 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  11/238 (4.62%)  10/231 (4.33%) 
Anuria  1  0/238 (0.00%)  1/231 (0.43%) 
Azotaemia  1  2/238 (0.84%)  3/231 (1.30%) 
Calculus ureteric  1  0/238 (0.00%)  1/231 (0.43%) 
Chronic kidney disease  1  0/238 (0.00%)  1/231 (0.43%) 
Dysuria  1  1/238 (0.42%)  1/231 (0.43%) 
Haematuria  1  4/238 (1.68%)  0/231 (0.00%) 
Hydronephrosis  1  0/238 (0.00%)  1/231 (0.43%) 
Nephrotic syndrome  1  1/238 (0.42%)  0/231 (0.00%) 
Proteinuria  1  0/238 (0.00%)  1/231 (0.43%) 
Renal failure  1  5/238 (2.10%)  3/231 (1.30%) 
Renal vein thrombosis  1  0/238 (0.00%)  1/231 (0.43%) 
Tubulointerstitial nephritis  1  1/238 (0.42%)  0/231 (0.00%) 
Urinary retention  1  2/238 (0.84%)  0/231 (0.00%) 
Urinary tract obstruction  1  1/238 (0.42%)  0/231 (0.00%) 
Reproductive system and breast disorders     
Oedema genital  1  0/238 (0.00%)  1/231 (0.43%) 
Pelvic pain  1  0/238 (0.00%)  1/231 (0.43%) 
Uterine haemorrhage  1  0/238 (0.00%)  1/231 (0.43%) 
Uterine polyp  1  0/238 (0.00%)  1/231 (0.43%) 
Vaginal haemorrhage  1  0/238 (0.00%)  1/231 (0.43%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  0/238 (0.00%)  1/231 (0.43%) 
Acute respiratory failure  1  0/238 (0.00%)  1/231 (0.43%) 
Bronchial disorder  1  0/238 (0.00%)  1/231 (0.43%) 
Chronic obstructive pulmonary disease  1  2/238 (0.84%)  1/231 (0.43%) 
Cough  1  2/238 (0.84%)  1/231 (0.43%) 
Dyspnoea  1  12/238 (5.04%)  13/231 (5.63%) 
Dyspnoea exertional  1  2/238 (0.84%)  0/231 (0.00%) 
Epistaxis  1  2/238 (0.84%)  3/231 (1.30%) 
Haemoptysis  1  4/238 (1.68%)  0/231 (0.00%) 
Hypoxia  1  2/238 (0.84%)  1/231 (0.43%) 
Interstitial lung disease  1  3/238 (1.26%)  0/231 (0.00%) 
Obstructive airways disorder  1  1/238 (0.42%)  0/231 (0.00%) 
Pleural effusion  1  10/238 (4.20%)  12/231 (5.19%) 
Pneumonia aspiration  1  1/238 (0.42%)  1/231 (0.43%) 
Pneumonitis  1  4/238 (1.68%)  0/231 (0.00%) 
Pneumothorax  1  1/238 (0.42%)  2/231 (0.87%) 
Pulmonary embolism  1  0/238 (0.00%)  3/231 (1.30%) 
Pulmonary granuloma  1  0/238 (0.00%)  1/231 (0.43%) 
Pulmonary haemorrhage  1  0/238 (0.00%)  1/231 (0.43%) 
Pulmonary oedema  1  1/238 (0.42%)  3/231 (1.30%) 
Respiratory failure  1  6/238 (2.52%)  1/231 (0.43%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  2/238 (0.84%)  0/231 (0.00%) 
Dermatitis  1  1/238 (0.42%)  0/231 (0.00%) 
Generalised erythema  1  1/238 (0.42%)  0/231 (0.00%) 
Skin ulcer  1  0/238 (0.00%)  1/231 (0.43%) 
Vascular disorders     
Aortic aneurysm  1  0/238 (0.00%)  1/231 (0.43%) 
Aortic dissection  1  0/238 (0.00%)  1/231 (0.43%) 
Hypertension  1  0/238 (0.00%)  4/231 (1.73%) 
Hypertensive crisis  1  0/238 (0.00%)  2/231 (0.87%) 
Hypotension  1  3/238 (1.26%)  1/231 (0.43%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Everolimus 1L/Sunitinib 2L Sunitinib 1L/Everolimus 2L
Affected / at Risk (%) Affected / at Risk (%)
Total   231/238 (97.06%)   228/231 (98.70%) 
Blood and lymphatic system disorders     
Anaemia  1  75/238 (31.51%)  70/231 (30.30%) 
Leukopenia  1  11/238 (4.62%)  14/231 (6.06%) 
Neutropenia  1  21/238 (8.82%)  45/231 (19.48%) 
Thrombocytopenia  1  37/238 (15.55%)  58/231 (25.11%) 
Endocrine disorders     
Hyperthyroidism  1  4/238 (1.68%)  14/231 (6.06%) 
Hypothyroidism  1  30/238 (12.61%)  57/231 (24.68%) 
Eye disorders     
Periorbital oedema  1  9/238 (3.78%)  12/231 (5.19%) 
Gastrointestinal disorders     
Abdominal discomfort  1  13/238 (5.46%)  8/231 (3.46%) 
Abdominal distension  1  19/238 (7.98%)  16/231 (6.93%) 
Abdominal pain  1  49/238 (20.59%)  41/231 (17.75%) 
Abdominal pain upper  1  32/238 (13.45%)  38/231 (16.45%) 
Aphthous stomatitis  1  14/238 (5.88%)  2/231 (0.87%) 
Constipation  1  66/238 (27.73%)  68/231 (29.44%) 
Diarrhoea  1  131/238 (55.04%)  140/231 (60.61%) 
Dry mouth  1  16/238 (6.72%)  22/231 (9.52%) 
Dyspepsia  1  37/238 (15.55%)  59/231 (25.54%) 
Dysphagia  1  16/238 (6.72%)  12/231 (5.19%) 
Gastritis  1  8/238 (3.36%)  13/231 (5.63%) 
Gastrooesophageal reflux disease  1  14/238 (5.88%)  28/231 (12.12%) 
Mouth ulceration  1  18/238 (7.56%)  14/231 (6.06%) 
Nausea  1  114/238 (47.90%)  125/231 (54.11%) 
Oral pain  1  12/238 (5.04%)  12/231 (5.19%) 
Stomatitis  1  134/238 (56.30%)  146/231 (63.20%) 
Toothache  1  15/238 (6.30%)  8/231 (3.46%) 
Vomiting  1  73/238 (30.67%)  76/231 (32.90%) 
General disorders     
Asthenia  1  44/238 (18.49%)  63/231 (27.27%) 
Chills  1  29/238 (12.18%)  20/231 (8.66%) 
Face oedema  1  16/238 (6.72%)  19/231 (8.23%) 
Fatigue  1  124/238 (52.10%)  131/231 (56.71%) 
Non-cardiac chest pain  1  33/238 (13.87%)  30/231 (12.99%) 
Oedema peripheral  1  79/238 (33.19%)  58/231 (25.11%) 
Pain  1  14/238 (5.88%)  11/231 (4.76%) 
Peripheral swelling  1  15/238 (6.30%)  10/231 (4.33%) 
Pyrexia  1  66/238 (27.73%)  48/231 (20.78%) 
Infections and infestations     
Bronchitis  1  12/238 (5.04%)  6/231 (2.60%) 
Influenza  1  16/238 (6.72%)  8/231 (3.46%) 
Nasopharyngitis  1  26/238 (10.92%)  18/231 (7.79%) 
Pneumonia  1  16/238 (6.72%)  10/231 (4.33%) 
Upper respiratory tract infection  1  25/238 (10.50%)  38/231 (16.45%) 
Urinary tract infection  1  21/238 (8.82%)  23/231 (9.96%) 
Investigations     
Alanine aminotransferase increased  1  16/238 (6.72%)  18/231 (7.79%) 
Aspartate aminotransferase increased  1  14/238 (5.88%)  12/231 (5.19%) 
Blood alkaline phosphatase increased  1  4/238 (1.68%)  12/231 (5.19%) 
Blood creatinine increased  1  34/238 (14.29%)  39/231 (16.88%) 
Gamma-glutamyltransferase increased  1  12/238 (5.04%)  16/231 (6.93%) 
Haemoglobin decreased  1  21/238 (8.82%)  26/231 (11.26%) 
Neutrophil count decreased  1  7/238 (2.94%)  15/231 (6.49%) 
Platelet count decreased  1  6/238 (2.52%)  17/231 (7.36%) 
Weight decreased  1  63/238 (26.47%)  49/231 (21.21%) 
Metabolism and nutrition disorders     
Decreased appetite  1  93/238 (39.08%)  101/231 (43.72%) 
Dehydration  1  19/238 (7.98%)  23/231 (9.96%) 
Hypercholesterolaemia  1  19/238 (7.98%)  12/231 (5.19%) 
Hyperglycaemia  1  41/238 (17.23%)  30/231 (12.99%) 
Hyperkalaemia  1  12/238 (5.04%)  14/231 (6.06%) 
Hypertriglyceridaemia  1  21/238 (8.82%)  15/231 (6.49%) 
Hypoalbuminaemia  1  13/238 (5.46%)  10/231 (4.33%) 
Hypokalaemia  1  14/238 (5.88%)  13/231 (5.63%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  50/238 (21.01%)  46/231 (19.91%) 
Back pain  1  60/238 (25.21%)  66/231 (28.57%) 
Bone pain  1  8/238 (3.36%)  15/231 (6.49%) 
Flank pain  1  23/238 (9.66%)  17/231 (7.36%) 
Muscle spasms  1  17/238 (7.14%)  11/231 (4.76%) 
Muscular weakness  1  15/238 (6.30%)  13/231 (5.63%) 
Musculoskeletal chest pain  1  15/238 (6.30%)  11/231 (4.76%) 
Musculoskeletal pain  1  29/238 (12.18%)  20/231 (8.66%) 
Myalgia  1  19/238 (7.98%)  22/231 (9.52%) 
Neck pain  1  10/238 (4.20%)  15/231 (6.49%) 
Pain in extremity  1  47/238 (19.75%)  44/231 (19.05%) 
Nervous system disorders     
Dizziness  1  40/238 (16.81%)  30/231 (12.99%) 
Dysgeusia  1  73/238 (30.67%)  75/231 (32.47%) 
Headache  1  58/238 (24.37%)  50/231 (21.65%) 
Hypoaesthesia  1  16/238 (6.72%)  10/231 (4.33%) 
Neuropathy peripheral  1  12/238 (5.04%)  14/231 (6.06%) 
Paraesthesia  1  12/238 (5.04%)  12/231 (5.19%) 
Psychiatric disorders     
Anxiety  1  21/238 (8.82%)  19/231 (8.23%) 
Depression  1  22/238 (9.24%)  13/231 (5.63%) 
Insomnia  1  41/238 (17.23%)  41/231 (17.75%) 
Renal and urinary disorders     
Dysuria  1  19/238 (7.98%)  15/231 (6.49%) 
Haematuria  1  12/238 (5.04%)  17/231 (7.36%) 
Proteinuria  1  6/238 (2.52%)  13/231 (5.63%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  96/238 (40.34%)  76/231 (32.90%) 
Dysphonia  1  13/238 (5.46%)  6/231 (2.60%) 
Dyspnoea  1  68/238 (28.57%)  57/231 (24.68%) 
Dyspnoea exertional  1  18/238 (7.56%)  14/231 (6.06%) 
Epistaxis  1  53/238 (22.27%)  54/231 (23.38%) 
Nasal congestion  1  12/238 (5.04%)  5/231 (2.16%) 
Oropharyngeal pain  1  28/238 (11.76%)  22/231 (9.52%) 
Pleural effusion  1  14/238 (5.88%)  11/231 (4.76%) 
Pneumonitis  1  16/238 (6.72%)  7/231 (3.03%) 
Productive cough  1  24/238 (10.08%)  19/231 (8.23%) 
Rhinorrhoea  1  26/238 (10.92%)  17/231 (7.36%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  15/238 (6.30%)  15/231 (6.49%) 
Dermatitis  1  4/238 (1.68%)  12/231 (5.19%) 
Dermatitis acneiform  1  20/238 (8.40%)  9/231 (3.90%) 
Dry skin  1  34/238 (14.29%)  38/231 (16.45%) 
Erythema  1  11/238 (4.62%)  18/231 (7.79%) 
Hair colour changes  1  6/238 (2.52%)  16/231 (6.93%) 
Nail disorder  1  13/238 (5.46%)  10/231 (4.33%) 
Night sweats  1  9/238 (3.78%)  13/231 (5.63%) 
Palmar-plantar erythrodysaesthesia syndrome  1  46/238 (19.33%)  92/231 (39.83%) 
Pruritus  1  43/238 (18.07%)  38/231 (16.45%) 
Rash  1  95/238 (39.92%)  67/231 (29.00%) 
Swelling face  1  12/238 (5.04%)  6/231 (2.60%) 
Yellow skin  1  12/238 (5.04%)  28/231 (12.12%) 
Vascular disorders     
Hypertension  1  61/238 (25.63%)  84/231 (36.36%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.0
PRO Tools - completed on Days 1 & 28 of a cycle. Assessments on D1 coincided with end of a 14-day break for patients on sunitinib but not everolimus. So D1 assessments of patients in sunitinib arm may be less impacted by potential toxicity effects.
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.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00903175     History of Changes
Other Study ID Numbers: CRAD001L2202
2009-011056-21 ( EudraCT Number )
First Submitted: April 24, 2009
First Posted: May 18, 2009
Results First Submitted: May 20, 2016
Results First Posted: June 28, 2016
Last Update Posted: November 8, 2016