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Trial record 10 of 1298 for:    survival | Neuroendocrine Tumors

Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors (RADIANT-3)

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ClinicalTrials.gov Identifier: NCT00510068
Recruitment Status : Completed
First Posted : August 1, 2007
Results First Posted : December 15, 2011
Last Update Posted : July 1, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Advanced Neuroendocrine Tumors of Pancreatic Origin
Interventions Drug: Everolimus
Drug: Everolimus Placebo
Enrollment 410
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1). Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Period Title: Double-blind Period
Started 207 203
Safety Population 204 203
Completed 0 0
Not Completed 207 203
Reason Not Completed
Disease progression             98             169
Final primary analysis             52             18
Adverse Event             37             7
Withdrawal by Subject             8             6
Death             4             3
Abnormal test result (s)             1             0
Lost to Follow-up             1             0
Protocol Violation             6             0
Period Title: Open-label Period
Started 225 [1] 0
Completed 0 0
Not Completed 225 0
Reason Not Completed
Disease Progression             124             0
Adverse Event             46             0
Withdrawal by Subject             21             0
Administrative problems             17             0
Death             7             0
New cancer therapy             7             0
Protocol Violation             2             0
Abnormal laboratory value (s)             1             0
[1]
172 patients switched over from placebo & 53 who were initially randomized to Everolimus arm.
Arm/Group Title Everolimus 10 mg/Day Placebo Total
Hide Arm/Group Description Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1). Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1). Total of all reporting groups
Overall Number of Baseline Participants 207 203 410
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 207 participants 203 participants 410 participants
57.1  (12.2) 56.2  (11.4) 56.6  (11.8)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 207 participants 203 participants 410 participants
<65 years 146 153 299
>=65 years 61 50 111
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 207 participants 203 participants 410 participants
Female
97
  46.9%
86
  42.4%
183
  44.6%
Male
110
  53.1%
117
  57.6%
227
  55.4%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 207 participants 203 participants 410 participants
Caucasian 156 166 322
Asian 40 34 74
Black 9 2 11
Other 2 1 3
1.Primary Outcome
Title Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology
Hide Description Progression of disease is defined as the time from study start to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria: Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.
Time Frame Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Median (95% Confidence Interval)
Unit of Measure: Months
11.04
(8.41 to 13.86)
4.60
(3.06 to 5.39)
2.Secondary Outcome
Title Percentage of Participants With Objective Response Rate ( CR {Complete Response} OR PR {Partial Response})
Hide Description Objective Response defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of the longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks . Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions
Time Frame Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
4.8
(2.3 to 8.7)
2.0
(0.5 to 5.0)
3.Secondary Outcome
Title Overall Survival
Hide Description Overall survival (OS) was defined as the time from date of randomization to the date of death due to any cause. Analyses were performed using all deaths in the FAS population regardless of whether they were observed during the double-blind treatment period, the open-label treatment period, the post-treatment evaluations, or the survival follow-up period.
Time Frame Baseline, to death- no time limit
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) included all randomized patients.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Median (95% Confidence Interval)
Unit of Measure: Months
44.02
(35.61 to 51.75)
37.68
(29.14 to 45.77)
4.Secondary Outcome
Title Progression Free Survival According to Ki-67 Levels Categorized as: Less Than or Equal to 2%, > 2% to Less Than or Equal to 5% and > 5%
Hide Description The level of Ki 67 expression for evaluable tumor samples were analyzed towards progression free survival (PFS) as per local investigator assessment. The Ki-67 protein is a cellular marker for proliferation. It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Baseline Ki 67 levels were categorized as: less than or equal to 2%, > 2% to less than or equal to 5% and > 5%.
Time Frame Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Median (95% Confidence Interval)
Unit of Measure: Months
Ki67 <=2% (n: 7, 17)
12.52
(3.42 to 14.75)
3.68
(2.86 to 5.52)
2% <Ki67 <=5% (n: 24, 13)
10.94
(5.55 to 16.59)
8.48
(3.78 to 13.83)
Ki67 >5% (n: 20, 22)
7.69 [1] 
(5.59 to NA)
3.15
(2.79 to 5.55)
[1]
Upper boundary of the 95% (Confidence Interval (CI) was not computable
5.Secondary Outcome
Title Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response
Hide Description Baseline levels of serum CgA SE were characterized towards progression free survival (PFS) as per local investigator assessment, relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated' otherwise considered as "Non-elevated". An ‘early response’ (applicable to only those patients with elevated levels at baseline) was defined as a decrease of greater than or equal to 30% from baseline to Cycle 2 Day 1 or normalization by Cycle 2 Day 1. CgA is widely expressed in well-differentiated pancreatic NET. CgA is present in the secretory granules of neuroendocrine cells. Pancreatic NET patients often present with elevated circulating levels of CgA in their blood. Baseline levels of these biomarkers are considered as prognostic factors.
Time Frame Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Median (95% Confidence Interval)
Unit of Measure: Months
CgA Levels at baseline: CgA <= 2x ULN (n:121, 97)
11.17
(8.54 to 16.49)
4.90
(2.99 to 5.55)
CgA levels at baseline: CgA > 2x ULN (n:84, 103)
8.54
(7.69 to 13.80)
4.34
(2.86 to 5.39)
Early CgA response: Response (n: 48, 22)
8.54
(7.56 to 14.00)
5.70
(3.19 to 8.54)
Early CgA response: Non-Response (n:40, 82)
11.14 [1] 
(6.90 to NA)
3.19
(2.83 to 5.36)
[1]
Upper boundary of the 95% Confidence Interval (CI) was not be computable
6.Secondary Outcome
Title Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response
Hide Description Baseline levels of serum NSE were characterized towards PFS as per local investigator assessment, relative to the upper limited of normal (ULN). NSE levels exceeding ULN were considered to be 'Elevated' otherwise considered as "Non-elevated". An ‘early response’ (applicable to only those patients with elevated levels at baseline) was defined as a decrease of greater than or equal to 30% from baseline to Cycle 2 Day 1 or normalization by Cycle 2 Day 1. NSE is widely expressed in well-differentiated pancreatic NET. NSE is usually expressed in the cytoplasm. Pancreatic NET patients often present with elevated circulating levels of NSE in their blood. Baseline levels of these biomarkers are considered as prognostic factors.
Time Frame Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consisted of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Median (95% Confidence Interval)
Unit of Measure: Months
NSE Levels at baseline: <= ULN (n: 155, 138)
13.86
(10.81 to 18.10)
5.36
(3.78 to 5.55)
NSE levels at baseline: > ULN (n: 48, 56)
8.11
(4.24 to 11.17)
2.83
(2.60 to 3.06)
Early NSE response: Response (n: 24, 16)
8.11
(4.24 to 11.40)
3.06
(2.23 to 5.36)
Early NSE response: Non-Response (n:16, 27)
3.79
(2.60 to 13.80)
2.58
(1.84 to 2.83)
7.Secondary Outcome
Title Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs)
Hide Description Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Time Frame on or after the start of double-blind study medication until no later than 28 days after double-blind study medication discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consists of all patients who received any study drug and had at least one post-baseline safety assessment.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 204 203
Measure Type: Number
Unit of Measure: Participants
Adverse events (AEs) 203 198
Death 111 23
Serious Adverse Events 84 52
8.Secondary Outcome
Title Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) (Open-label Period)
Hide Description Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Time Frame on or after the start of open-label study medication until no later than 28 days after open-label study medication discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The open-label set was used to summarize the safety analyses performed on data collected in the open-label period of the study: the open-label set included only patients who received at least one dose of open-label everolimus 10 mg and had at least one safety assessment during the open-label period of the study.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 225 0
Measure Type: Number
Unit of Measure: Participants
Adverse events (AEs) 221
Death 122
Serious Adverse Events 108
9.Secondary Outcome
Title Evaluation of Pharmacokinetics (PK) Parameter: AUC0-t Last
Hide Description The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. This PK parameter is area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t last).
Time Frame Day 1 of every cycle (28 days/cycle) throughout the study
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all patients who received any study drug and had at least one postbaseline safety assessment.
Arm/Group Title Everolimus 10 mg/Day Everolimus 5 mg/Day
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received 5 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 7 1
Mean (Standard Deviation)
Unit of Measure: ng.h/mL
594  (313) 481 [1]   (NA)
[1]
Summary statistics were only produced if the sample size for the dose group in the respective cycle is 3 or more.
10.Secondary Outcome
Title Evaluation of Pharmacokinetics (PK) Parameters: Cmax, Cmin
Hide Description The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameter: maximum (peak) drug concentration (Cmax) and minimum (trough) drug concentration (Cmin).
Time Frame Day 1 of every cycle (28 days/cycle) throughout the study
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all patients who received any study drug and had at least one postbaseline safety assessment.
Arm/Group Title Everolimus 10 mg/Day Everolimus 5 mg/Day
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received 5 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 7 1
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cmax 62.4  (18.5) 27.4 [1]   (NA)
Cmin 9.80  (4.95) 12.2 [1]   (NA)
[1]
Summary statistics will only be produced if the sample size for the dose group in the respective cycle is 3 or more.
11.Secondary Outcome
Title Evaluation of Pharmacokinetics (PK) Parameter: CL/F
Hide Description The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameter clearance of distribution expressed as a function of bioavailability (CL/F).
Time Frame Day 1 of every cycle (28 days/cycle) throughout the study
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all patients who received any study drug and had at least one postbaseline safety assessment.
Arm/Group Title Everolimus 10 mg/Day Everolimus 5 mg/Day
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received 5 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 7 1
Mean (Standard Deviation)
Unit of Measure: L/h
20.2  (7.7) 10.7 [1]   (NA)
[1]
Summary statistics were only produced if the sample size for the dose group in the respective cycle is 3 or more.
12.Secondary Outcome
Title Evaluation of Pharmacokinetics (PK) Parameter: Tmax -Time to Maximum (Peak) Drug Concentration
Hide Description The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. Values for tmax where summarized in median (range).
Time Frame Day 1 of every cycle (28 days/cycle) throughout the study
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all patients who received any study drug and had at least one postbaseline safety assessment.
Arm/Group Title Everolimus 10 mg/Day Everolimus 5 mg/Day
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received 5 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 7 1
Median (Full Range)
Unit of Measure: h
1.17
(0.5 to 24.0)
3.0 [1] 
(NA to NA)
[1]
Summary statistics were only produced if the sample size for the dose group in the respective cycle is 3 or more.
13.Secondary Outcome
Title Analysis of Time to Definitive Deterioration of WHO Performance Status Using Kaplan-Meier
Hide Description Time to definitive worsening is defined as a definitive increase in performance status from a baseline of 0 or 1 to WHO >= 2, or from a baseline value of 2 to WHO >= 3. If no earlier deterioration, patients were censored at the end of follow-up or at the start of further antineoplastic therapy. Rates of patients with no deterioration at 3 and 6 months were computed using Kaplan-meier method. Grade 0: Able to carry out all activity without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory & able to do light work; Grade 2: Ambulatory & capable of all self-care but unable to carry out any work. Up & about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled & cannot carry on any self-care; totally confined to bed or chair.
Time Frame 3 months, 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Measure Type: Number
Unit of Measure: % of participants with no deterioration
Month 3 94.4 91.8
Month 6 90.6 86.3
14.Secondary Outcome
Title Plasma Angiogenesis Marker: Basic Fibroblast Growth Factor (bFGF)
Hide Description This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline (n:198, 195) 52.59  (101.659) 51.49  (78.049)
Cycle 2 Day 1 (n: 185, 184) 38.43  (51.809) 58.33  (72.938)
Cycle 3 Day 1 (n: 185, 174) 51.97  (89.064) 59.08  (72.495)
Cycle 4 Day 1 (n: 171, 159) 51.28  (82.139) 54.58  (75.350)
15.Secondary Outcome
Title Plasma Angiogenesis Marker: Placental Growth Factor (PLGF)
Hide Description This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline (n:198, 195) 45.82  (282.084) 32.92  (52.586)
Cycle 2 Day 1 (n: 185, 184) 25.78  (33.420) 35.38  (57.135)
Cycle 3 Day 1 (n: 185, 174) 26.55  (28.839) 33.84  (65.361)
Cycle 4 Day 1 (n: 171, 159) 25.69  (18.312) 35.47  (67.314)
16.Secondary Outcome
Title Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1)
Hide Description This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline (n:198, 195) 264.18  (272.190) 256.69  (187.866)
Cycle 2 Day 1 (n: 185, 184) 307.46  (808.316) 299.03  (541.933)
Cycle 3 Day 1 (n: 185, 174) 263.81  (187.329) 253.37  (250.841)
Cycle 4 Day 1 (n: 171, 159) 258.03  (223.980) 242.17  (163.561)
17.Secondary Outcome
Title Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)
Hide Description This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline (n:197, 193) 30061.30  (8607.379) 31299.61  (9091.460)
Cycle 2 Day 1 (n: 185, 183) 22691.18  (6793.409) 30223.21  (8447.992)
Cycle 3 Day 1 (n: 185, 173) 22021.23  (6393.414) 29264.67  (8408.405)
Cycle 4 Day 1 (n: 172, 158) 21218.17  (6249.977) 28308.58  (8477.049)
18.Secondary Outcome
Title Plasma Angiogenesis Marker: Vascular Endothelial Growth Factor (VEGF)
Hide Description This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Time Frame Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) consists of all patients who were randomized.
Arm/Group Title Everolimus 10 mg/Day Placebo
Hide Arm/Group Description:
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Overall Number of Participants Analyzed 207 203
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline (n:198, 195) 265.09  (283.123) 326.16  (323.891)
Cycle 2 Day 1 (n: 185, 184) 243.03  (183.010) 326.78  (377.752)
Cycle 3 Day 1 (n: 185, 174) 280.18  (268.582) 292.27  (286.154)
Cycle 4 Day 1 (n: 171, 159) 283.51  (326.634) 319.60  (325.409)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Everolimus 10mg/Day Placebo Open Label - Everolimus 10mg
Hide Arm/Group Description Afinitor DB: Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1). Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1). Afinitor OL (for data collected in the open-label period of the study): The open-label set included only patients who received at least one dose of open-label everolimus 10 mg and had at least one safety assessment during the open-label period of the study.
All-Cause Mortality
Everolimus 10mg/Day Placebo Open Label - Everolimus 10mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Everolimus 10mg/Day Placebo Open Label - Everolimus 10mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   84/204 (41.18%)   52/203 (25.62%)   108/225 (48.00%) 
Blood and lymphatic system disorders       
Anaemia  1  7/204 (3.43%)  3/203 (1.48%)  3/225 (1.33%) 
Febrile neutropenia  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Lymphadenopathy  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Microcytic anaemia  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Neutropenia  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Thrombocytopenia  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Cardiac disorders       
Acute coronary syndrome  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Angina pectoris  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Atrial flutter  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Cardiac arrest  1  2/204 (0.98%)  0/203 (0.00%)  1/225 (0.44%) 
Cardiac failure  1  2/204 (0.98%)  1/203 (0.49%)  0/225 (0.00%) 
Cardiac failure congestive  1  2/204 (0.98%)  0/203 (0.00%)  1/225 (0.44%) 
Cardio-respiratory arrest  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Coronary artery stenosis  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Left ventricular dysfunction  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Myocardial infarction  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Myocarditis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Palpitations  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Pericardial effusion  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Right ventricular dysfunction  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Right ventricular failure  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Supraventricular tachycardia  1  0/204 (0.00%)  0/203 (0.00%)  3/225 (1.33%) 
Tricuspid valve incompetence  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Congenital, familial and genetic disorders       
Branchial cyst  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Ear and labyrinth disorders       
Deafness  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Endocrine disorders       
Adrenal insufficiency  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Hypercalcaemia of malignancy  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Eye disorders       
Cataract  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Macular fibrosis  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Ophthalmoplegia  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Gastrointestinal disorders       
Abdominal discomfort  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Abdominal distension  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Abdominal hernia  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Abdominal hernia obstructive  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Abdominal pain  1  6/204 (2.94%)  5/203 (2.46%)  13/225 (5.78%) 
Abdominal pain upper  1  2/204 (0.98%)  2/203 (0.99%)  3/225 (1.33%) 
Abdominal rigidity  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Ascites  1  3/204 (1.47%)  0/203 (0.00%)  0/225 (0.00%) 
Colitis  1  2/204 (0.98%)  0/203 (0.00%)  0/225 (0.00%) 
Colitis ischaemic  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Diarrhoea  1  5/204 (2.45%)  2/203 (0.99%)  3/225 (1.33%) 
Duodenal stenosis  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Dyspepsia  1  0/204 (0.00%)  1/203 (0.49%)  1/225 (0.44%) 
Enterocolitis  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Gastritis  1  0/204 (0.00%)  0/203 (0.00%)  2/225 (0.89%) 
Gastritis erosive  1  1/204 (0.49%)  1/203 (0.49%)  0/225 (0.00%) 
Gastrointestinal haemorrhage  1  1/204 (0.49%)  2/203 (0.99%)  5/225 (2.22%) 
Gastrooesophageal reflux disease  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Haematemesis  1  1/204 (0.49%)  1/203 (0.49%)  0/225 (0.00%) 
Ileus  1  1/204 (0.49%)  1/203 (0.49%)  1/225 (0.44%) 
Ileus paralytic  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Intestinal dilatation  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Melaena  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Nausea  1  3/204 (1.47%)  4/203 (1.97%)  7/225 (3.11%) 
Oesophageal haemorrhage  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Oesophageal stenosis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Oesophageal varices haemorrhage  1  1/204 (0.49%)  1/203 (0.49%)  1/225 (0.44%) 
Pancreatitis  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Pancreatitis acute  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Peptic ulcer haemorrhage  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Rectal haemorrhage  1  0/204 (0.00%)  2/203 (0.99%)  1/225 (0.44%) 
Small intestinal haemorrhage  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Small intestinal obstruction  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Stomatitis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Subileus  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Swollen tongue  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Tongue oedema  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Upper gastrointestinal haemorrhage  1  2/204 (0.98%)  1/203 (0.49%)  1/225 (0.44%) 
Vomiting  1  2/204 (0.98%)  4/203 (1.97%)  10/225 (4.44%) 
General disorders       
Asthenia  1  5/204 (2.45%)  2/203 (0.99%)  6/225 (2.67%) 
Chest pain  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Chills  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Death  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Device occlusion  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Fatigue  1  0/204 (0.00%)  2/203 (0.99%)  1/225 (0.44%) 
General physical health deterioration  1  1/204 (0.49%)  1/203 (0.49%)  3/225 (1.33%) 
Generalised oedema  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Influenza like illness  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Malaise  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Multi-organ failure  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Non-cardiac chest pain  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Oedema  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Oedema peripheral  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Performance status decreased  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Pyrexia  1  8/204 (3.92%)  3/203 (1.48%)  8/225 (3.56%) 
Sudden death  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Thrombosis in device  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Hepatobiliary disorders       
Bile duct obstruction  1  0/204 (0.00%)  1/203 (0.49%)  2/225 (0.89%) 
Bile duct stenosis  1  0/204 (0.00%)  1/203 (0.49%)  1/225 (0.44%) 
Cholangitis  1  2/204 (0.98%)  0/203 (0.00%)  5/225 (2.22%) 
Cholangitis acute  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Cholecystitis acute  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Cholecystitis chronic  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Cholelithiasis  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Cholestasis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Hepatic failure  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Hepatic necrosis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Hepatotoxicity  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Hyperbilirubinaemia  1  1/204 (0.49%)  1/203 (0.49%)  1/225 (0.44%) 
Jaundice  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Jaundice cholestatic  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Immune system disorders       
Anaphylactic reaction  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Anaphylactic shock  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Drug hypersensitivity  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Infections and infestations       
Arthritis bacterial  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Atypical pneumonia  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Bacteraemia  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Bacterial infection  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Biliary tract infection  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Campylobacter infection  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Cellulitis  1  0/204 (0.00%)  0/203 (0.00%)  3/225 (1.33%) 
Cholecystitis infective  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Clostridium difficile infection  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Cystitis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Diverticulitis  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Enterococcal bacteraemia  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Escherichia sepsis  1  2/204 (0.98%)  0/203 (0.00%)  0/225 (0.00%) 
Escherichia urinary tract infection  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Gastroenteritis  1  2/204 (0.98%)  2/203 (0.99%)  2/225 (0.89%) 
Gastroenteritis viral  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Infection  1  3/204 (1.47%)  0/203 (0.00%)  1/225 (0.44%) 
Liver abscess  1  1/204 (0.49%)  0/203 (0.00%)  2/225 (0.89%) 
Lobar pneumonia  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Lung infection  1  0/204 (0.00%)  0/203 (0.00%)  2/225 (0.89%) 
Perihepatic abscess  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Pilonidal cyst  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Pneumonia  1  3/204 (1.47%)  2/203 (0.99%)  10/225 (4.44%) 
Pneumonia mycoplasmal  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Post procedural infection  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Pulmonary tuberculosis  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Sepsis  1  0/204 (0.00%)  1/203 (0.49%)  1/225 (0.44%) 
Septic shock  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Sinusitis  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Staphylococcal sepsis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Streptococcal sepsis  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Subcutaneous abscess  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Tonsillitis  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Urinary tract infection  1  0/204 (0.00%)  0/203 (0.00%)  2/225 (0.89%) 
Viral infection  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Wound infection staphylococcal  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Injury, poisoning and procedural complications       
Femoral neck fracture  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Foot fracture  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Hip fracture  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Incisional hernia  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Intentional overdose  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Overdose  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Patella fracture  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Procedural pain  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Rib fracture  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Wound complication  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Wound secretion  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Investigations       
Alanine aminotransferase increased  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Ammonia increased  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Aspartate aminotransferase increased  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Blood bilirubin increased  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Blood creatinine increased  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Blood potassium decreased  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
C-reactive protein increased  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Haemoglobin decreased  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Weight decreased  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  2/204 (0.98%)  0/203 (0.00%)  3/225 (1.33%) 
Dehydration  1  5/204 (2.45%)  2/203 (0.99%)  2/225 (0.89%) 
Diabetes mellitus  1  1/204 (0.49%)  1/203 (0.49%)  3/225 (1.33%) 
Diabetes mellitus inadequate control  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Diabetic ketoacidosis  1  0/204 (0.00%)  0/203 (0.00%)  2/225 (0.89%) 
Electrolyte imbalance  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Fluid overload  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Gout  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Hypercalcaemia  1  2/204 (0.98%)  3/203 (1.48%)  0/225 (0.00%) 
Hyperglycaemia  1  2/204 (0.98%)  2/203 (0.99%)  3/225 (1.33%) 
Hyperkalaemia  1  1/204 (0.49%)  1/203 (0.49%)  0/225 (0.00%) 
Hypoglycaemia  1  0/204 (0.00%)  1/203 (0.49%)  4/225 (1.78%) 
Hypokalaemia  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Hyponatraemia  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Hypophagia  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Hypophosphataemia  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Ketoacidosis  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Metabolic acidosis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Polydipsia  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/204 (0.00%)  1/203 (0.49%)  1/225 (0.44%) 
Back pain  1  1/204 (0.49%)  2/203 (0.99%)  2/225 (0.89%) 
Bone pain  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Flank pain  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Neck pain  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Pain in extremity  1  0/204 (0.00%)  2/203 (0.99%)  0/225 (0.00%) 
Polyarthritis  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Rhabdomyolysis  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Spinal osteoarthritis  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Spinal pain  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Bladder cancer  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Cancer pain  1  0/204 (0.00%)  2/203 (0.99%)  0/225 (0.00%) 
Gastrinoma  1  0/204 (0.00%)  0/203 (0.00%)  2/225 (0.89%) 
Malignant melanoma  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Neuroendocrine tumour  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Pancreatic neuroendocrine tumour metastatic  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Nervous system disorders       
Ataxia  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Cerebrovascular accident  1  1/204 (0.49%)  0/203 (0.00%)  3/225 (1.33%) 
Depressed level of consciousness  1  0/204 (0.00%)  2/203 (0.99%)  1/225 (0.44%) 
Dizziness  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Epiduritis  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Hepatic encephalopathy  1  1/204 (0.49%)  0/203 (0.00%)  2/225 (0.89%) 
Hypoglycaemic coma  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Loss of consciousness  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Memory impairment  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Mental impairment  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Sciatica  1  1/204 (0.49%)  1/203 (0.49%)  0/225 (0.00%) 
Syncope  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Tremor  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Unresponsive to stimuli  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Psychiatric disorders       
Confusional state  1  3/204 (1.47%)  3/203 (1.48%)  2/225 (0.89%) 
Listless  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Mental status changes  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Renal and urinary disorders       
Calculus urinary  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Haematuria  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Nephrolithiasis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Pollakiuria  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Polyuria  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Pyelocaliectasis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Renal colic  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Renal failure  1  3/204 (1.47%)  1/203 (0.49%)  1/225 (0.44%) 
Renal failure acute  1  2/204 (0.98%)  3/203 (1.48%)  4/225 (1.78%) 
Renal impairment  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Renal tubular necrosis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory distress syndrome  1  1/204 (0.49%)  0/203 (0.00%)  1/225 (0.44%) 
Bronchial hyperreactivity  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Cough  1  2/204 (0.98%)  1/203 (0.49%)  1/225 (0.44%) 
Dyspnoea  1  6/204 (2.94%)  2/203 (0.99%)  2/225 (0.89%) 
Haemoptysis  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Hypoxia  1  1/204 (0.49%)  1/203 (0.49%)  0/225 (0.00%) 
Interstitial lung disease  1  3/204 (1.47%)  0/203 (0.00%)  1/225 (0.44%) 
Lung infiltration  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Nasal obstruction  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Pleural effusion  1  2/204 (0.98%)  1/203 (0.49%)  1/225 (0.44%) 
Pleurisy  1  0/204 (0.00%)  1/203 (0.49%)  1/225 (0.44%) 
Pneumonitis  1  7/204 (3.43%)  0/203 (0.00%)  2/225 (0.89%) 
Pneumothorax  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Pulmonary congestion  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Pulmonary embolism  1  5/204 (2.45%)  1/203 (0.49%)  1/225 (0.44%) 
Pulmonary hypertension  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Pulmonary oedema  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Respiratory failure  1  2/204 (0.98%)  1/203 (0.49%)  2/225 (0.89%) 
Skin and subcutaneous tissue disorders       
Rash  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Stasis dermatitis  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Vascular disorders       
Aneurysm ruptured  1  0/204 (0.00%)  0/203 (0.00%)  1/225 (0.44%) 
Hypertensive crisis  1  0/204 (0.00%)  1/203 (0.49%)  0/225 (0.00%) 
Hypotension  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Venous thrombosis  1  1/204 (0.49%)  0/203 (0.00%)  0/225 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Everolimus 10mg/Day Placebo Open Label - Everolimus 10mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   201/204 (98.53%)   190/203 (93.60%)   218/225 (96.89%) 
Blood and lymphatic system disorders       
Anaemia  1  48/204 (23.53%)  18/203 (8.87%)  55/225 (24.44%) 
Leukopenia  1  12/204 (5.88%)  4/203 (1.97%)  9/225 (4.00%) 
Lymphopenia  1  15/204 (7.35%)  6/203 (2.96%)  10/225 (4.44%) 
Neutropenia  1  14/204 (6.86%)  4/203 (1.97%)  24/225 (10.67%) 
Thrombocytopenia  1  29/204 (14.22%)  2/203 (0.99%)  20/225 (8.89%) 
Gastrointestinal disorders       
Abdominal distension  1  18/204 (8.82%)  14/203 (6.90%)  19/225 (8.44%) 
Abdominal pain  1  47/204 (23.04%)  48/203 (23.65%)  55/225 (24.44%) 
Abdominal pain upper  1  30/204 (14.71%)  15/203 (7.39%)  29/225 (12.89%) 
Aphthous stomatitis  1  25/204 (12.25%)  8/203 (3.94%)  22/225 (9.78%) 
Ascites  1  13/204 (6.37%)  4/203 (1.97%)  7/225 (3.11%) 
Constipation  1  30/204 (14.71%)  26/203 (12.81%)  32/225 (14.22%) 
Diarrhoea  1  97/204 (47.55%)  47/203 (23.15%)  96/225 (42.67%) 
Dry mouth  1  23/204 (11.27%)  9/203 (4.43%)  8/225 (3.56%) 
Dyspepsia  1  13/204 (6.37%)  13/203 (6.40%)  8/225 (3.56%) 
Flatulence  1  10/204 (4.90%)  8/203 (3.94%)  14/225 (6.22%) 
Gastrooesophageal reflux disease  1  5/204 (2.45%)  6/203 (2.96%)  13/225 (5.78%) 
Haemorrhoids  1  6/204 (2.94%)  4/203 (1.97%)  17/225 (7.56%) 
Mouth ulceration  1  14/204 (6.86%)  4/203 (1.97%)  15/225 (6.67%) 
Nausea  1  66/204 (32.35%)  64/203 (31.53%)  80/225 (35.56%) 
Stomatitis  1  110/204 (53.92%)  27/203 (13.30%)  105/225 (46.67%) 
Toothache  1  11/204 (5.39%)  5/203 (2.46%)  10/225 (4.44%) 
Vomiting  1  61/204 (29.90%)  41/203 (20.20%)  70/225 (31.11%) 
General disorders       
Asthenia  1  35/204 (17.16%)  40/203 (19.70%)  41/225 (18.22%) 
Chills  1  11/204 (5.39%)  1/203 (0.49%)  14/225 (6.22%) 
Fatigue  1  91/204 (44.61%)  53/203 (26.11%)  73/225 (32.44%) 
Influenza like illness  1  9/204 (4.41%)  3/203 (1.48%)  16/225 (7.11%) 
Oedema peripheral  1  76/204 (37.25%)  23/203 (11.33%)  66/225 (29.33%) 
Pyrexia  1  56/204 (27.45%)  23/203 (11.33%)  57/225 (25.33%) 
Infections and infestations       
Bronchitis  1  4/204 (1.96%)  3/203 (1.48%)  15/225 (6.67%) 
Influenza  1  6/204 (2.94%)  7/203 (3.45%)  12/225 (5.33%) 
Nasopharyngitis  1  33/204 (16.18%)  14/203 (6.90%)  38/225 (16.89%) 
Pneumonia  1  11/204 (5.39%)  0/203 (0.00%)  13/225 (5.78%) 
Sinusitis  1  14/204 (6.86%)  4/203 (1.97%)  17/225 (7.56%) 
Upper respiratory tract infection  1  16/204 (7.84%)  7/203 (3.45%)  28/225 (12.44%) 
Urinary tract infection  1  23/204 (11.27%)  11/203 (5.42%)  23/225 (10.22%) 
Investigations       
Alanine aminotransferase increased  1  10/204 (4.90%)  9/203 (4.43%)  17/225 (7.56%) 
Aspartate aminotransferase increased  1  12/204 (5.88%)  11/203 (5.42%)  28/225 (12.44%) 
Blood alkaline phosphatase increased  1  12/204 (5.88%)  11/203 (5.42%)  25/225 (11.11%) 
Blood creatinine increased  1  10/204 (4.90%)  4/203 (1.97%)  15/225 (6.67%) 
Haemoglobin decreased  1  15/204 (7.35%)  2/203 (0.99%)  16/225 (7.11%) 
Weight decreased  1  58/204 (28.43%)  24/203 (11.82%)  72/225 (32.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  59/204 (28.92%)  37/203 (18.23%)  64/225 (28.44%) 
Dehydration  1  10/204 (4.90%)  7/203 (3.45%)  22/225 (9.78%) 
Diabetes mellitus  1  20/204 (9.80%)  0/203 (0.00%)  21/225 (9.33%) 
Hypercholesterolaemia  1  26/204 (12.75%)  2/203 (0.99%)  16/225 (7.11%) 
Hyperglycaemia  1  40/204 (19.61%)  21/203 (10.34%)  58/225 (25.78%) 
Hyperlipidaemia  1  16/204 (7.84%)  2/203 (0.99%)  10/225 (4.44%) 
Hypoglycaemia  1  11/204 (5.39%)  7/203 (3.45%)  10/225 (4.44%) 
Hypokalaemia  1  17/204 (8.33%)  5/203 (2.46%)  11/225 (4.89%) 
Hypophosphataemia  1  20/204 (9.80%)  3/203 (1.48%)  21/225 (9.33%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  31/204 (15.20%)  14/203 (6.90%)  34/225 (15.11%) 
Back pain  1  31/204 (15.20%)  22/203 (10.84%)  40/225 (17.78%) 
Muscle spasms  1  21/204 (10.29%)  8/203 (3.94%)  15/225 (6.67%) 
Musculoskeletal chest pain  1  12/204 (5.88%)  4/203 (1.97%)  15/225 (6.67%) 
Musculoskeletal pain  1  12/204 (5.88%)  9/203 (4.43%)  17/225 (7.56%) 
Myalgia  1  15/204 (7.35%)  14/203 (6.90%)  17/225 (7.56%) 
Pain in extremity  1  29/204 (14.22%)  10/203 (4.93%)  22/225 (9.78%) 
Nervous system disorders       
Dizziness  1  24/204 (11.76%)  16/203 (7.88%)  18/225 (8.00%) 
Dysgeusia  1  38/204 (18.63%)  11/203 (5.42%)  46/225 (20.44%) 
Headache  1  62/204 (30.39%)  30/203 (14.78%)  52/225 (23.11%) 
Psychiatric disorders       
Depression  1  14/204 (6.86%)  3/203 (1.48%)  18/225 (8.00%) 
Insomnia  1  28/204 (13.73%)  17/203 (8.37%)  27/225 (12.00%) 
Renal and urinary disorders       
Proteinuria  1  10/204 (4.90%)  2/203 (0.99%)  13/225 (5.78%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  45/204 (22.06%)  21/203 (10.34%)  54/225 (24.00%) 
Dyspnoea  1  33/204 (16.18%)  13/203 (6.40%)  34/225 (15.11%) 
Epistaxis  1  44/204 (21.57%)  3/203 (1.48%)  38/225 (16.89%) 
Oropharyngeal pain  1  23/204 (11.27%)  12/203 (5.91%)  29/225 (12.89%) 
Pleural effusion  1  12/204 (5.88%)  2/203 (0.99%)  6/225 (2.67%) 
Pneumonitis  1  21/204 (10.29%)  0/203 (0.00%)  17/225 (7.56%) 
Skin and subcutaneous tissue disorders       
Acne  1  13/204 (6.37%)  5/203 (2.46%)  15/225 (6.67%) 
Alopecia  1  8/204 (3.92%)  9/203 (4.43%)  12/225 (5.33%) 
Dermatitis acneiform  1  9/204 (4.41%)  2/203 (0.99%)  13/225 (5.78%) 
Dry skin  1  26/204 (12.75%)  12/203 (5.91%)  28/225 (12.44%) 
Erythema  1  11/204 (5.39%)  3/203 (1.48%)  4/225 (1.78%) 
Nail disorder  1  28/204 (13.73%)  2/203 (0.99%)  26/225 (11.56%) 
Onychoclasis  1  14/204 (6.86%)  2/203 (0.99%)  12/225 (5.33%) 
Pruritus  1  40/204 (19.61%)  26/203 (12.81%)  42/225 (18.67%) 
Rash  1  107/204 (52.45%)  32/203 (15.76%)  90/225 (40.00%) 
Vascular disorders       
Flushing  1  4/204 (1.96%)  6/203 (2.96%)  12/225 (5.33%) 
Hypertension  1  24/204 (11.76%)  9/203 (4.43%)  29/225 (12.89%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, 16.1
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 the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00510068     History of Changes
Other Study ID Numbers: CRAD001C2324
2006-006819-75 ( EudraCT Number )
First Submitted: July 31, 2007
First Posted: August 1, 2007
Results First Submitted: November 11, 2011
Results First Posted: December 15, 2011
Last Update Posted: July 1, 2015