Trial Outcomes & Findings for Safety and Efficacy of RAD001 (Everolimus) Monotherapy Plus Best Supportive Care in Patients With Advanced Gastric Cancer (AGC) (NCT NCT00879333)
NCT ID: NCT00879333
Last Updated: 2015-11-03
Results Overview
The primary objective of this study was to compare OS between everolimus + best supportive care (BSC) and placebo + BSC. OS, was defined as the time from date of randomization to the date of death due to any cause. If at the analysis cut-off date a patient was not known to have died, survival was censored at the date of the last contact. OS was analyzed using the Kaplan Meier estimates method.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
656 participants
Primary outcome timeframe
2.5 years
Results posted on
2015-11-03
Participant Flow
Participant milestones
| Measure |
Everolimus 10mg/Daily
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
|---|---|---|
|
Overall Study
STARTED
|
439
|
217
|
|
Overall Study
Discontinued Study Treatment
|
428
|
217
|
|
Overall Study
COMPLETED
|
11
|
0
|
|
Overall Study
NOT COMPLETED
|
428
|
217
|
Reasons for withdrawal
| Measure |
Everolimus 10mg/Daily
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
|---|---|---|
|
Overall Study
Adverse Event
|
94
|
34
|
|
Overall Study
Abnormal Laboratory Value
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
20
|
7
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Administrative Problems
|
2
|
0
|
|
Overall Study
Death
|
16
|
5
|
|
Overall Study
Disease Progression
|
292
|
169
|
|
Overall Study
Protocol Violation
|
1
|
1
|
Baseline Characteristics
Safety and Efficacy of RAD001 (Everolimus) Monotherapy Plus Best Supportive Care in Patients With Advanced Gastric Cancer (AGC)
Baseline characteristics by cohort
| Measure |
Everolimus 10mg/Daily
n=439 Participants
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
n=217 Participants
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Total
n=656 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.3 years
STANDARD_DEVIATION 11.59 • n=5 Participants
|
60.8 years
STANDARD_DEVIATION 11.61 • n=7 Participants
|
60.4 years
STANDARD_DEVIATION 11.59 • n=5 Participants
|
|
Age, Customized
< 65 years
|
260 Participants
n=5 Participants
|
129 Participants
n=7 Participants
|
389 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
179 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
267 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
117 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
173 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
322 Participants
n=5 Participants
|
161 Participants
n=7 Participants
|
483 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
166 Participants
n=5 Participants
|
75 Participants
n=7 Participants
|
241 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
251 Participants
n=5 Participants
|
126 Participants
n=7 Participants
|
377 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
19 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2.5 yearsPopulation: The Full Analysis Set (FAS) consists of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum that they were assigned to at randomization.
The primary objective of this study was to compare OS between everolimus + best supportive care (BSC) and placebo + BSC. OS, was defined as the time from date of randomization to the date of death due to any cause. If at the analysis cut-off date a patient was not known to have died, survival was censored at the date of the last contact. OS was analyzed using the Kaplan Meier estimates method.
Outcome measures
| Measure |
Everolimus 10mg/Daily
n=439 Participants
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
n=217 Participants
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
|---|---|---|
|
Overall Survival (OS)
|
5.39 Months
Interval 4.8 to 6.01
|
4.34 Months
Interval 3.81 to 5.49
|
SECONDARY outcome
Timeframe: 2.5 yearsPopulation: The Full Analysis Set (FAS) consists of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum that they were assigned to at randomization.
Progression free survival 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, where progression was based on Investigator assessment of baseline and post-baseline scans according to RECIST. Progression free survival was censored if no PFS event was observed before the first to occur out of (i) the cut-off date, or (ii) the date when a further anticancer therapy was started. The censoring date was the date of the last adequate tumor assessment before either of these two events occurred. If a PFS event was observed after two or more missing or non-evaluable tumor assessments, then the date of progression was censored at the date of the last adequate tumor assessment; for a PFS event observed after a single missing or non-evaluable tumor assessment, the actual date of disease progression was used. Anslsis was done using Kaplan-Meier estimates method.
Outcome measures
| Measure |
Everolimus 10mg/Daily
n=439 Participants
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
n=217 Participants
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
|---|---|---|
|
Progression Free Survival (PFS)
|
1.68 Months
Interval 1.51 to 1.94
|
1.41 Months
Interval 1.38 to 1.45
|
SECONDARY outcome
Timeframe: 2.5 yearsPopulation: The Full Analysis Set (FAS) consists of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum that they were assigned to at randomization.
The EORTC QLQ-C30 global health status/quality of life sub-scale (QL) was pre-specified as the primary domain of interest, followed by physical functioning (PF), social functioning (SF) and emotional functioning (EF).The EORTC QLQ-C30 questionnaire, along with a module specific for gastric cancer patients (EORTC QLQ-STO22), was used to evaluate PRO. The QLQ-C30 has five function scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and a global health status/quality of life scale. In addition, there are questions that assess specific symptoms. The QLQ-STO22 consists of 22 questions that make up five multi-item scales (dysphagia, pain, reflux, eating and anxiety) and four single-item scales (dry mouth, tasting, body image and hair loss).
Outcome measures
| Measure |
Everolimus 10mg/Daily
n=439 Participants
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
n=217 Participants
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
|---|---|---|
|
Patient Reported Outcome (PRO): Time to Definitive Deterioration of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Scores
In QL score by at least 5 % compared to baseline
|
1.51 Months
Interval 1.28 to 1.84
|
1.45 Months
Interval 1.05 to 1.68
|
|
Patient Reported Outcome (PRO): Time to Definitive Deterioration of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Scores
In PF score by at least 5 % compared to baseline
|
1.35 Months
Interval 1.12 to 1.54
|
1.15 Months
Interval 1.02 to 1.64
|
|
Patient Reported Outcome (PRO): Time to Definitive Deterioration of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Scores
In SF score by at least 5 % compared to baseline
|
1.87 Months
Interval 1.84 to 2.3
|
1.87 Months
Interval 1.64 to 2.46
|
|
Patient Reported Outcome (PRO): Time to Definitive Deterioration of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Scores
In EF score by at least 5 % compared to baseline
|
1.84 Months
Interval 1.61 to 2.1
|
1.71 Months
Interval 1.41 to 1.87
|
SECONDARY outcome
Timeframe: 2.5 yearsPopulation: The Full Analysis Set (FAS) consists of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum that they were assigned to at randomization.
The ECOG PS scale was used to classify patients according to their functional impairment, with scores ranging from 0 (fully active) to 5 (dead). An analysis of the time to definitive deterioration of the ECOG PS by one category of the score from baseline was performed. Definitive deterioration was defined as a definitive increase by one category from baseline in ECOG PS, with no later improvements observed during the course of the study. A single measure reporting an increase in ECOG PS is sufficient to consider it as a definitive worsening only if it was the last one available for the patient. Kaplan-Meier method was used to estimate the distribution function of time to definitive worsening.
Outcome measures
| Measure |
Everolimus 10mg/Daily
n=439 Participants
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
n=217 Participants
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
|---|---|---|
|
Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
|
2.30 Months
Interval 1.97 to 2.79
|
2.23 Months
Interval 1.87 to 2.92
|
SECONDARY outcome
Timeframe: 2.5 yearsPopulation: The Full Analysis Set (FAS) consists of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum that they were assigned to at randomization.
ORR was defined as the proportion of patients with measurable disease in whom best overall response (OR) was either complete response (CR) or partial response (PR) according to RECIST criteria.
Outcome measures
| Measure |
Everolimus 10mg/Daily
n=439 Participants
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
n=217 Participants
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
|---|---|---|
|
Overall Response Rate (ORR)
Measurable Disease
|
379 Participants
|
191 Participants
|
|
Overall Response Rate (ORR)
Complete Response (CR)
|
1 Participants
|
0 Participants
|
|
Overall Response Rate (ORR)
Partial Response (PR)
|
16 Participants
|
4 Participants
|
|
Overall Response Rate (ORR)
Overall Response Rate (ORR)
|
17 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Week 5Population: PK analyses were based on the safety population in patients with evaluable samples. Only valid pre-dose (Cmin) \& Cmax everolimus samples were included. For patients who were unable to tolerate the protocol-specified dosing schedule, dose adjustments were allowed to keep the patient on study drug. Some patients had dose reductions to 5mg daily.
Cmin is the minimum (trough) steady-state drug concentration in the blood during multiple dosing and Cmax is the maximum (peak) blood drug concentration after dose administration. Cmax is estimated as the maximum of C1h and C2H. C1h is 1 hour post-dose blood concentration and C2h is 2 hour post-dose blood concentration. Only valid pre-dose (Cmin), C1h, and C2h everolimus samples were included in the analysis. Valid pre-dose samples were confirmed blood samples collected at steady-state, collected immediately prior to dosing on the same study day, and collected at approximately 24 ± 4 hours after the previous dose and with no vomiting within the first 4 hours following the last dose. Valid C1h and C2h samples were confirmed blood samples collected at steady-state and within ± 1 hour window and with no vomiting within the first 4 hours following the current and previous dose.
Outcome measures
| Measure |
Everolimus 10mg/Daily
n=218 Participants
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
n=18 Participants
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
|---|---|---|
|
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax at Week 5
Pre-dose (Cmin) (n: 201,18)
|
16.143 ng/mL
Standard Deviation 10.7723
|
10.498 ng/mL
Standard Deviation 6.1432
|
|
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax at Week 5
Cmax (n: 218,16)
|
72.775 ng/mL
Standard Deviation 36.5435
|
37.269 ng/mL
Standard Deviation 27.2086
|
SECONDARY outcome
Timeframe: Week 5Population: PK analyses were based on the safety population in patients with evaluable samples. Only valid pre-dose (Cmin) \& Cmax everolimus samples were included. For patients who were unable to tolerate the protocol-specified dosing schedule, dose adjustments were allowed to keep the patient on study drug. Some patients had dose reductions to 5mg daily.
Cmin is the minimum (trough) steady-state drug concentration in the blood during multiple dosing and Cmax is the maximum (peak) blood drug concentration after dose administration. Cmax is estimated as the maximum of C1h and C2H. C1h is 1 hour post-dose blood concentration and C2h is 2 hour post-dose blood concentration. Only valid pre-dose (Cmin), C1h, and C2h everolimus samples were included in the analysis. Valid pre-dose samples were confirmed blood samples collected at steady-state, collected immediately prior to dosing on the same study day, and collected at approximately 24 ± 4 hours after the previous dose and with no vomiting within the first 4 hours following the last dose. Valid C1h and C2h samples were confirmed blood samples collected at steady-state and within ± 1 hour window and with no vomiting within the first 4 hours following the current and previous dose.
Outcome measures
| Measure |
Everolimus 10mg/Daily
n=218 Participants
All patients were randomized to receive everolimus + BSC. All patients orally took two 5 mg tablets of everolimus once daily. Therefore, all patients in the everolimus arm took a total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
Placebo
n=18 Participants
All patients were randomized to receive placebo + BSC. All patients orally took two 5 mg tablets of matching placebo once daily. Therefore, all patients in the placebo receive matching tablets of total daily dose of 10 mg. Best supportive care was in accordance with the local practice of an individual institution or center, and specifically excluded anti-cancer treatments.
|
|---|---|---|
|
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax by Region Asia vs. Rest of the World (ROW) at Week 5
Asia: Pre-dose (n:127, 11)
|
16.804 ng/mL
Standard Deviation 9.6163
|
9.921 ng/mL
Standard Deviation 5.1565
|
|
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax by Region Asia vs. Rest of the World (ROW) at Week 5
Asia: Cmax (n:132, 10)
|
73.568 ng/mL
Standard Deviation 34.1898
|
34.580 ng/mL
Standard Deviation 26.8110
|
|
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax by Region Asia vs. Rest of the World (ROW) at Week 5
Rest of the World: Pre-dose (n:74, 7)
|
15.009 ng/mL
Standard Deviation 12.5000
|
11.406 ng/mL
Standard Deviation 7.8128
|
|
Everolimus Steady State Concentraions at Predose (Cmin) and Cmax by Region Asia vs. Rest of the World (ROW) at Week 5
Rest of the World: Cmax (n:86, 6)
|
71.558 ng/mL
Standard Deviation 40.0655
|
41.750 ng/mL
Standard Deviation 29.8074
|
Adverse Events
Everolimus 10mg / Daily
Serious events: 210 serious events
Other events: 416 other events
Deaths: 0 deaths
Placebo
Serious events: 89 serious events
Other events: 193 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Everolimus 10mg / Daily
n=437 participants at risk
Everolimus 10mg / daily
|
Placebo
n=215 participants at risk
Placebo
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
3.4%
15/437
|
0.93%
2/215
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.23%
1/437
|
0.00%
0/215
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.46%
2/437
|
0.00%
0/215
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.46%
2/437
|
0.00%
0/215
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.23%
1/437
|
0.00%
0/215
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.69%
3/437
|
0.00%
0/215
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.23%
1/437
|
0.00%
0/215
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.92%
4/437
|
0.47%
1/215
|
|
Cardiac disorders
Atrial fibrillation
|
0.23%
1/437
|
0.00%
0/215
|
|
Cardiac disorders
Cardiac arrest
|
0.46%
2/437
|
0.00%
0/215
|
|
Cardiac disorders
Cardiac disorder
|
0.00%
0/437
|
0.47%
1/215
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.23%
1/437
|
0.00%
0/215
|
|
Cardiac disorders
Myocardial ischaemia
|
0.23%
1/437
|
0.00%
0/215
|
|
Cardiac disorders
Palpitations
|
0.23%
1/437
|
0.00%
0/215
|
|
Congenital, familial and genetic disorders
Pyloric stenosis
|
0.23%
1/437
|
0.47%
1/215
|
|
Eye disorders
Retinal detachment
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Abdominal adhesions
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Abdominal compartment syndrome
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Abdominal distension
|
0.46%
2/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Abdominal pain
|
4.8%
21/437
|
5.6%
12/215
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.46%
2/437
|
0.93%
2/215
|
|
Gastrointestinal disorders
Abdominal rigidity
|
0.00%
0/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Ascites
|
2.1%
9/437
|
1.9%
4/215
|
|
Gastrointestinal disorders
Chronic gastrointestinal bleeding
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Colitis
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/437
|
0.93%
2/215
|
|
Gastrointestinal disorders
Diarrhoea
|
1.4%
6/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Duodenal perforation
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Dyspepsia
|
0.69%
3/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Dysphagia
|
1.1%
5/437
|
0.93%
2/215
|
|
Gastrointestinal disorders
Enteritis
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Faecaloma
|
0.46%
2/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Gastric perforation
|
0.46%
2/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Gastric stenosis
|
0.00%
0/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
3.0%
13/437
|
1.4%
3/215
|
|
Gastrointestinal disorders
Gastrointestinal obstruction
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Gastrointestinal toxicity
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Haematemesis
|
0.46%
2/437
|
1.4%
3/215
|
|
Gastrointestinal disorders
Ileus
|
1.1%
5/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Internal hernia
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.1%
5/437
|
2.3%
5/215
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.69%
3/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Mallory-Weiss syndrome
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Melaena
|
0.23%
1/437
|
1.4%
3/215
|
|
Gastrointestinal disorders
Nausea
|
2.1%
9/437
|
4.2%
9/215
|
|
Gastrointestinal disorders
Obstruction gastric
|
0.46%
2/437
|
0.93%
2/215
|
|
Gastrointestinal disorders
Oesophageal perforation
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Peritoneal adhesions
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Peritoneal disorder
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Peritoneal haemorrhage
|
0.00%
0/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Rectal obstruction
|
0.23%
1/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/437
|
1.4%
3/215
|
|
Gastrointestinal disorders
Stomatitis
|
0.69%
3/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Subileus
|
0.46%
2/437
|
0.47%
1/215
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.69%
3/437
|
0.00%
0/215
|
|
Gastrointestinal disorders
Vomiting
|
3.2%
14/437
|
4.7%
10/215
|
|
General disorders
Asthenia
|
2.7%
12/437
|
2.8%
6/215
|
|
General disorders
Chest discomfort
|
0.23%
1/437
|
0.00%
0/215
|
|
General disorders
Device dislocation
|
0.23%
1/437
|
0.00%
0/215
|
|
General disorders
Device malfunction
|
0.00%
0/437
|
0.47%
1/215
|
|
General disorders
Device occlusion
|
0.46%
2/437
|
0.00%
0/215
|
|
General disorders
Drug intolerance
|
0.23%
1/437
|
0.00%
0/215
|
|
General disorders
Facial pain
|
0.23%
1/437
|
0.00%
0/215
|
|
General disorders
Fatigue
|
1.8%
8/437
|
1.9%
4/215
|
|
General disorders
General physical health deterioration
|
3.2%
14/437
|
1.9%
4/215
|
|
General disorders
Hyperthermia
|
0.46%
2/437
|
0.00%
0/215
|
|
General disorders
Local swelling
|
0.23%
1/437
|
0.00%
0/215
|
|
General disorders
Malaise
|
0.46%
2/437
|
0.00%
0/215
|
|
General disorders
Multi-organ failure
|
0.23%
1/437
|
0.47%
1/215
|
|
General disorders
Non-cardiac chest pain
|
0.46%
2/437
|
0.00%
0/215
|
|
General disorders
Oedema peripheral
|
0.00%
0/437
|
0.93%
2/215
|
|
General disorders
Performance status decreased
|
0.23%
1/437
|
0.00%
0/215
|
|
General disorders
Pyrexia
|
2.3%
10/437
|
0.47%
1/215
|
|
General disorders
Stent malfunction
|
0.00%
0/437
|
0.47%
1/215
|
|
General disorders
Systemic inflammatory response syndrome
|
0.23%
1/437
|
0.00%
0/215
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.46%
2/437
|
0.47%
1/215
|
|
Hepatobiliary disorders
Cholangitis
|
0.69%
3/437
|
0.00%
0/215
|
|
Hepatobiliary disorders
Cholangitis acute
|
0.23%
1/437
|
0.00%
0/215
|
|
Hepatobiliary disorders
Cholestasis
|
0.00%
0/437
|
0.47%
1/215
|
|
Hepatobiliary disorders
Hepatic failure
|
0.23%
1/437
|
0.47%
1/215
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.23%
1/437
|
0.47%
1/215
|
|
Hepatobiliary disorders
Hepatitis
|
0.23%
1/437
|
0.00%
0/215
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.92%
4/437
|
2.3%
5/215
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.46%
2/437
|
0.00%
0/215
|
|
Infections and infestations
Acinetobacter infection
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Biliary sepsis
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/437
|
0.47%
1/215
|
|
Infections and infestations
Clostridium difficile colitis
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Device related infection
|
0.46%
2/437
|
0.00%
0/215
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.00%
0/437
|
0.47%
1/215
|
|
Infections and infestations
Gastric infection
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Gastroenteritis
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Herpes zoster
|
0.23%
1/437
|
0.47%
1/215
|
|
Infections and infestations
Infection
|
0.00%
0/437
|
0.47%
1/215
|
|
Infections and infestations
Liver abscess
|
0.46%
2/437
|
0.00%
0/215
|
|
Infections and infestations
Lower respiratory tract infection
|
0.69%
3/437
|
0.00%
0/215
|
|
Infections and infestations
Lung infection
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Oral herpes
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Peritonitis
|
0.46%
2/437
|
0.00%
0/215
|
|
Infections and infestations
Peritonitis bacterial
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Pneumocystis jirovecii pneumonia
|
0.46%
2/437
|
0.00%
0/215
|
|
Infections and infestations
Pneumonia
|
2.7%
12/437
|
1.9%
4/215
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Pyelonephritis acute
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Sepsis
|
0.46%
2/437
|
0.93%
2/215
|
|
Infections and infestations
Septic shock
|
0.92%
4/437
|
0.00%
0/215
|
|
Infections and infestations
Skin infection
|
0.23%
1/437
|
0.00%
0/215
|
|
Infections and infestations
Streptococcal sepsis
|
0.00%
0/437
|
0.47%
1/215
|
|
Infections and infestations
Urinary tract infection
|
0.92%
4/437
|
0.00%
0/215
|
|
Infections and infestations
Urosepsis
|
0.00%
0/437
|
0.93%
2/215
|
|
Injury, poisoning and procedural complications
Colon injury
|
0.23%
1/437
|
0.00%
0/215
|
|
Injury, poisoning and procedural complications
Compression fracture
|
0.23%
1/437
|
0.00%
0/215
|
|
Injury, poisoning and procedural complications
Hepatic rupture
|
0.00%
0/437
|
0.47%
1/215
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.23%
1/437
|
0.00%
0/215
|
|
Injury, poisoning and procedural complications
Muscle injury
|
0.23%
1/437
|
0.00%
0/215
|
|
Injury, poisoning and procedural complications
Oesophageal injury
|
0.23%
1/437
|
0.00%
0/215
|
|
Injury, poisoning and procedural complications
Post procedural haematuria
|
0.23%
1/437
|
0.00%
0/215
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.23%
1/437
|
0.00%
0/215
|
|
Injury, poisoning and procedural complications
Subdural haemorrhage
|
0.23%
1/437
|
0.00%
0/215
|
|
Investigations
Alanine aminotransferase increased
|
0.23%
1/437
|
0.00%
0/215
|
|
Investigations
Aspartate aminotransferase increased
|
0.23%
1/437
|
0.00%
0/215
|
|
Investigations
Blood creatinine increased
|
0.23%
1/437
|
0.47%
1/215
|
|
Investigations
C-reactive protein increased
|
0.23%
1/437
|
0.00%
0/215
|
|
Investigations
General physical condition abnormal
|
0.23%
1/437
|
0.00%
0/215
|
|
Investigations
Haemoglobin decreased
|
0.23%
1/437
|
0.00%
0/215
|
|
Investigations
International normalised ratio increased
|
0.23%
1/437
|
0.00%
0/215
|
|
Investigations
Transaminases increased
|
0.23%
1/437
|
0.00%
0/215
|
|
Metabolism and nutrition disorders
Cachexia
|
0.23%
1/437
|
0.47%
1/215
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.8%
21/437
|
3.7%
8/215
|
|
Metabolism and nutrition disorders
Dehydration
|
0.69%
3/437
|
0.93%
2/215
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.23%
1/437
|
0.00%
0/215
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.23%
1/437
|
0.00%
0/215
|
|
Metabolism and nutrition disorders
Feeding disorder
|
0.00%
0/437
|
0.47%
1/215
|
|
Metabolism and nutrition disorders
Fluid intake reduced
|
0.23%
1/437
|
0.00%
0/215
|
|
Metabolism and nutrition disorders
Food intolerance
|
0.23%
1/437
|
0.47%
1/215
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.23%
1/437
|
0.00%
0/215
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.23%
1/437
|
0.00%
0/215
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.23%
1/437
|
0.00%
0/215
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.23%
1/437
|
0.00%
0/215
|
|
Metabolism and nutrition disorders
Hypophagia
|
0.23%
1/437
|
0.47%
1/215
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.23%
1/437
|
0.00%
0/215
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.23%
1/437
|
0.00%
0/215
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.1%
5/437
|
0.93%
2/215
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.23%
1/437
|
0.00%
0/215
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.23%
1/437
|
0.47%
1/215
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.23%
1/437
|
0.00%
0/215
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.23%
1/437
|
0.00%
0/215
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.23%
1/437
|
0.00%
0/215
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.46%
2/437
|
0.00%
0/215
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangiosis carcinomatosa
|
0.23%
1/437
|
0.00%
0/215
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.23%
1/437
|
0.00%
0/215
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever
|
0.23%
1/437
|
0.00%
0/215
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.69%
3/437
|
0.00%
0/215
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour perforation
|
0.23%
1/437
|
0.00%
0/215
|
|
Nervous system disorders
Brain stem infarction
|
0.00%
0/437
|
0.47%
1/215
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/437
|
0.47%
1/215
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/437
|
0.47%
1/215
|
|
Nervous system disorders
Dizziness
|
0.23%
1/437
|
0.93%
2/215
|
|
Nervous system disorders
Headache
|
0.23%
1/437
|
0.00%
0/215
|
|
Nervous system disorders
Hemiplegia
|
0.00%
0/437
|
0.47%
1/215
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/437
|
0.47%
1/215
|
|
Nervous system disorders
Paraparesis
|
0.00%
0/437
|
0.47%
1/215
|
|
Nervous system disorders
Syncope
|
0.46%
2/437
|
0.00%
0/215
|
|
Psychiatric disorders
Anxiety
|
0.23%
1/437
|
0.00%
0/215
|
|
Psychiatric disorders
Confusional state
|
0.46%
2/437
|
0.00%
0/215
|
|
Psychiatric disorders
Expressive language disorder
|
0.00%
0/437
|
0.47%
1/215
|
|
Renal and urinary disorders
Haematuria
|
0.23%
1/437
|
0.00%
0/215
|
|
Renal and urinary disorders
Hydronephrosis
|
0.23%
1/437
|
0.00%
0/215
|
|
Renal and urinary disorders
Renal failure
|
0.46%
2/437
|
0.00%
0/215
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/437
|
0.47%
1/215
|
|
Renal and urinary disorders
Renal impairment
|
0.23%
1/437
|
1.9%
4/215
|
|
Renal and urinary disorders
Ureteric obstruction
|
0.23%
1/437
|
0.00%
0/215
|
|
Renal and urinary disorders
Urinary incontinence
|
0.23%
1/437
|
0.00%
0/215
|
|
Reproductive system and breast disorders
Scrotal oedema
|
0.23%
1/437
|
0.00%
0/215
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.23%
1/437
|
0.00%
0/215
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.1%
9/437
|
1.4%
3/215
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.46%
2/437
|
0.93%
2/215
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.46%
2/437
|
0.00%
0/215
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
2.1%
9/437
|
1.4%
3/215
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/437
|
0.47%
1/215
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.69%
3/437
|
0.00%
0/215
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.23%
1/437
|
0.00%
0/215
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.46%
2/437
|
0.93%
2/215
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
0.23%
1/437
|
0.00%
0/215
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.23%
1/437
|
0.00%
0/215
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.23%
1/437
|
0.00%
0/215
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.92%
4/437
|
0.00%
0/215
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
0.00%
0/437
|
0.47%
1/215
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/437
|
0.47%
1/215
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.46%
2/437
|
0.00%
0/215
|
|
Vascular disorders
Circulatory collapse
|
0.23%
1/437
|
0.00%
0/215
|
|
Vascular disorders
Deep vein thrombosis
|
0.23%
1/437
|
0.00%
0/215
|
|
Vascular disorders
Extremity necrosis
|
0.23%
1/437
|
0.00%
0/215
|
|
Vascular disorders
Hypertension
|
0.23%
1/437
|
0.00%
0/215
|
|
Vascular disorders
Hypotension
|
0.69%
3/437
|
0.47%
1/215
|
|
Vascular disorders
Hypovolaemic shock
|
0.00%
0/437
|
0.47%
1/215
|
|
Vascular disorders
Lymphoedema
|
0.23%
1/437
|
0.00%
0/215
|
|
Vascular disorders
Pallor
|
0.00%
0/437
|
0.47%
1/215
|
|
Vascular disorders
Pelvic venous thrombosis
|
0.23%
1/437
|
0.00%
0/215
|
|
Vascular disorders
Peripheral ischaemia
|
0.23%
1/437
|
0.00%
0/215
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/437
|
0.47%
1/215
|
|
Vascular disorders
Thrombosis
|
0.00%
0/437
|
0.47%
1/215
|
Other adverse events
| Measure |
Everolimus 10mg / Daily
n=437 participants at risk
Everolimus 10mg / daily
|
Placebo
n=215 participants at risk
Placebo
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
24.7%
108/437
|
19.5%
42/215
|
|
Blood and lymphatic system disorders
Leukopenia
|
6.9%
30/437
|
1.4%
3/215
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.8%
47/437
|
2.8%
6/215
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
17.6%
77/437
|
1.9%
4/215
|
|
Gastrointestinal disorders
Abdominal distension
|
8.9%
39/437
|
9.3%
20/215
|
|
Gastrointestinal disorders
Abdominal pain
|
20.6%
90/437
|
22.8%
49/215
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.7%
51/437
|
12.1%
26/215
|
|
Gastrointestinal disorders
Constipation
|
21.1%
92/437
|
19.1%
41/215
|
|
Gastrointestinal disorders
Diarrhoea
|
25.6%
112/437
|
15.3%
33/215
|
|
Gastrointestinal disorders
Dyspepsia
|
5.0%
22/437
|
3.7%
8/215
|
|
Gastrointestinal disorders
Nausea
|
29.5%
129/437
|
29.3%
63/215
|
|
Gastrointestinal disorders
Stomatitis
|
39.6%
173/437
|
10.2%
22/215
|
|
Gastrointestinal disorders
Vomiting
|
22.4%
98/437
|
25.1%
54/215
|
|
General disorders
Asthenia
|
15.3%
67/437
|
8.4%
18/215
|
|
General disorders
Fatigue
|
33.4%
146/437
|
29.3%
63/215
|
|
General disorders
Oedema peripheral
|
11.2%
49/437
|
9.8%
21/215
|
|
General disorders
Pyrexia
|
17.6%
77/437
|
11.2%
24/215
|
|
Investigations
Alanine aminotransferase increased
|
6.4%
28/437
|
4.2%
9/215
|
|
Investigations
Aspartate aminotransferase increased
|
7.8%
34/437
|
3.7%
8/215
|
|
Investigations
Blood alkaline phosphatase increased
|
7.8%
34/437
|
2.8%
6/215
|
|
Investigations
Weight decreased
|
19.9%
87/437
|
8.8%
19/215
|
|
Metabolism and nutrition disorders
Decreased appetite
|
46.2%
202/437
|
35.3%
76/215
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.1%
31/437
|
2.8%
6/215
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
5.7%
25/437
|
5.6%
12/215
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
11.9%
52/437
|
4.2%
9/215
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.5%
46/437
|
7.4%
16/215
|
|
Nervous system disorders
Dizziness
|
5.0%
22/437
|
5.6%
12/215
|
|
Nervous system disorders
Dysgeusia
|
5.9%
26/437
|
3.3%
7/215
|
|
Nervous system disorders
Headache
|
7.3%
32/437
|
3.7%
8/215
|
|
Psychiatric disorders
Insomnia
|
11.7%
51/437
|
10.2%
22/215
|
|
Renal and urinary disorders
Proteinuria
|
5.5%
24/437
|
2.3%
5/215
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.4%
50/437
|
7.9%
17/215
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.4%
54/437
|
9.8%
21/215
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.6%
29/437
|
0.47%
1/215
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
5.3%
23/437
|
3.3%
7/215
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
5.0%
22/437
|
0.93%
2/215
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.8%
47/437
|
4.2%
9/215
|
|
Skin and subcutaneous tissue disorders
Rash
|
19.7%
86/437
|
8.8%
19/215
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI 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.
- Publication restrictions are in place
Restriction type: OTHER