Trial Outcomes & Findings for Study of Everolimus (RAD001) in Patients With Recurrent Glioblastoma Multiforme (GBM) (NCT NCT00515086)
NCT ID: NCT00515086
Last Updated: 2011-09-22
Results Overview
In the Surgery Group, the primary efficacy assessment was inhibition of Mammalian target of rapamycin (mTOR) as defined as ≥75% S6 phosphorylation. The occurrence of S6 phosphorylation was determined by phosphor-S6 immunohistochemical staining. Tumor cells from the initial surgical resection and from the salvage resection were used for assessments.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
41 participants
Primary outcome timeframe
Baseline and Day 7-9 (during salvage surgery)
Results posted on
2011-09-22
Participant Flow
Eligible participants were separated into 2 Groups: Group 1 (Surgery Group) patients were scheduled for salvage surgery and randomly assigned to one of 3 pre-surgery treatment groups: 0, 5 or 10 mg/day Everolimus for 7 days. Group 2 (No Surgery Group) patients were not scheduled for salvage surgery and received 10 mg/day Everolimus.
Participant milestones
| Measure |
No Surgery (Everolimus 10 mg)
Participants with recurrent Glioblastoma Multiforme (GBM) not scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus (RAD001) until evidence of disease progression or toxicity.
|
Everolimus 10 mg + Surgery
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 5 mg + Surgery
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 0 mg + Surgery
Participants scheduled to undergo salvage surgical resection, received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
24
|
6
|
5
|
6
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
24
|
6
|
5
|
6
|
Reasons for withdrawal
| Measure |
No Surgery (Everolimus 10 mg)
Participants with recurrent Glioblastoma Multiforme (GBM) not scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus (RAD001) until evidence of disease progression or toxicity.
|
Everolimus 10 mg + Surgery
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 5 mg + Surgery
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 0 mg + Surgery
Participants scheduled to undergo salvage surgical resection, received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
2
|
3
|
|
Overall Study
Administrative
|
1
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
1
|
|
Overall Study
Unsatisfactory therapeutic effect
|
18
|
3
|
3
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
0
|
|
Overall Study
Study drug no longer required
|
0
|
1
|
0
|
0
|
|
Overall Study
Death
|
2
|
0
|
0
|
0
|
Baseline Characteristics
Study of Everolimus (RAD001) in Patients With Recurrent Glioblastoma Multiforme (GBM)
Baseline characteristics by cohort
| Measure |
No Surgery (Everolimus 10 mg)
n=24 Participants
Participants with recurrent Glioblastoma Multiforme (GBM) not scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus (RAD001) until evidence of disease progression or toxicity.
|
Everolimus 10 mg + Surgery
n=6 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 5 mg + Surgery
n=5 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 0 mg + Surgery
n=6 Participants
Participants scheduled to undergo salvage surgical resection, received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
29 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 7-9 (during salvage surgery)Population: Study was terminated due to slow enrollment.
In the Surgery Group, the primary efficacy assessment was inhibition of Mammalian target of rapamycin (mTOR) as defined as ≥75% S6 phosphorylation. The occurrence of S6 phosphorylation was determined by phosphor-S6 immunohistochemical staining. Tumor cells from the initial surgical resection and from the salvage resection were used for assessments.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: First day of treatment to study discontinuation (up to 60 weeks)Population: No Surgery Group participants from the Intent-to-treat (ITT) population who received at least one dose of study medication.
The best overall tumor response is reported for participants with 1 previous relapse and participants with ≥2 previous relapses according to the following categories: Complete Response, Partial Response, Stable Disease and Progressive Disease. Gadolinium chelate-enhanced Magnetic Resonance Imaging (MRI) was used for tumor analysis. The objective assessment of tumor response was evaluated at each site by the designated pathologist based on the Neuro-Oncology criteria for Tumor Response for Central Nervous System (CNS) tumors.
Outcome measures
| Measure |
Everolimus 10 mg + Surgery
n=12 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 5 mg + Surgery
n=12 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 0 mg + Surgery
Participants scheduled to undergo salvage surgical resection, received no treatment with Everolimus prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Total
All the participants scheduled to undergo salvage surgical resection from three pre-surgery treatment groups (i.e 0, 5 or 10 mg/day (once daily) everolimus X 7 days).
|
|---|---|---|---|---|
|
No Surgery Group: Best Overall Tumor Response
Complete response + Partial response
|
0 Participants
|
0 Participants
|
—
|
—
|
|
No Surgery Group: Best Overall Tumor Response
Complete response
|
0 Participants
|
0 Participants
|
—
|
—
|
|
No Surgery Group: Best Overall Tumor Response
Partial response
|
0 Participants
|
0 Participants
|
—
|
—
|
|
No Surgery Group: Best Overall Tumor Response
Stable disease
|
3 Participants
|
6 Participants
|
—
|
—
|
|
No Surgery Group: Best Overall Tumor Response
Progressive disease
|
7 Participants
|
6 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline and Day 7-9 (Blood samples were collected one day prior to surgery and tissue samples were collected during surgery.)Population: Study was terminated due to slow enrollment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: After surgery (within 96 hours), Weeks 4 and 8 and then every 8 weeks after restarting treatment until study discontinuation (Up to 28 weeks)Population: Results for the Surgery Group only include patients with residual tumor following salvage surgery.
Progression-free survival (PFS) was assessed using Gadolinium chelate-enhanced Magnetic Resonance Imaging (MRI) and based on the Neuro-Oncology Criteria for Tumor Response for CNS tumors. PFS was measured from the first day of treatment after surgery to disease progression or death and is derived using the Kaplan-Meier method.
Outcome measures
| Measure |
Everolimus 10 mg + Surgery
n=6 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 5 mg + Surgery
n=4 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 0 mg + Surgery
n=6 Participants
Participants scheduled to undergo salvage surgical resection, received no treatment with Everolimus prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Total
n=16 Participants
All the participants scheduled to undergo salvage surgical resection from three pre-surgery treatment groups (i.e 0, 5 or 10 mg/day (once daily) everolimus X 7 days).
|
|---|---|---|---|---|
|
Surgery Group: Progression-free Survival
|
25.9 Weeks
Interval 8.7 to 27.1
|
9.1 Weeks
Interval 5.6 to 14.9
|
NA Weeks
Interval 14.3 to
Because most participants (5) were censored in the no treatment group, the median and upper level limit of the 95% Confidence Interval for Progression-free survival could not be calculated.
|
14.9 Weeks
Interval 9.1 to 27.1
|
SECONDARY outcome
Timeframe: After surgery, week 4, week 8 and every 8 weeks thereafterPopulation: Study was terminated due to slow enrollment.
The secondary efficacy assessment was to evaluate the role of PTEN and EGFR pathway status on phosphor-S6. Tumor cells from the initial surgical resection and from the salvage resection were used for assessments. Immunohistochemistry and Fluorescence in-situ hybridization (FISH) were used to assess PTEN and EGFR pathway status. Study was terminated due to slow enrollment. Analysis was not possible due to insufficient sample size.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: First day of treatment to study discontinuation (up to 60 weeks)Population: No Surgery Group participants from the Intent-to-treat (ITT) population who received at least one dose of study medication.
Progression-free survival (PFS) was assessed using Gadolinium chelate-enhanced Magnetic Resonance Imaging (MRI) and based on the Neuro-Oncology Criteria for Tumor Response for CNS tumors. PFS is reported for participants with 1 previous relapse and participants with ≥2 previous relapses. PFS was measured from the first day of treatment to disease progression or death and is derived using the Kaplan-Meier method.
Outcome measures
| Measure |
Everolimus 10 mg + Surgery
n=12 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 5 mg + Surgery
n=12 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 0 mg + Surgery
n=24 Participants
Participants scheduled to undergo salvage surgical resection, received no treatment with Everolimus prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Total
All the participants scheduled to undergo salvage surgical resection from three pre-surgery treatment groups (i.e 0, 5 or 10 mg/day (once daily) everolimus X 7 days).
|
|---|---|---|---|---|
|
No Surgery Group: Progression Free Survival
|
4.14 Weeks
Interval 3.7 to 7.0
|
4.14 Weeks
Interval 3.9 to 12.0
|
4.14 Weeks
Interval 4.0 to 5.9
|
—
|
SECONDARY outcome
Timeframe: First day of treatment to study discontinuation (Up to 28 weeks)Population: Surgery Group participants from the Safety population who received at least one dose of study medication.
The number of participants with any adverse event by System Organ Class. Additional information about Adverse Events can be found in the Adverse Event Section.
Outcome measures
| Measure |
Everolimus 10 mg + Surgery
n=6 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 5 mg + Surgery
n=5 Participants
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 0 mg + Surgery
n=6 Participants
Participants scheduled to undergo salvage surgical resection, received no treatment with Everolimus prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Total
All the participants scheduled to undergo salvage surgical resection from three pre-surgery treatment groups (i.e 0, 5 or 10 mg/day (once daily) everolimus X 7 days).
|
|---|---|---|---|---|
|
Surgery Group: Number of Participants With Adverse Events
Gastrointestinal disorders
|
5 Participants
|
5 Participants
|
3 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Nervous system disorders
|
4 Participants
|
5 Participants
|
5 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
General disorders & administration site conditions
|
4 Participants
|
4 Participants
|
5 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Metabolism and nutrition disorders
|
6 Participants
|
4 Participants
|
3 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Blood and lymphatic system disorders
|
4 Participants
|
2 Participants
|
5 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Infections and infestations
|
4 Participants
|
2 Participants
|
3 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Psychiatric disorders
|
5 Participants
|
3 Participants
|
2 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Skin and subcutaneous tissue disorders
|
4 Participants
|
2 Participants
|
2 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Investigations
|
3 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Injury, poisoning, and procedural complications
|
5 Participants
|
3 Participants
|
0 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Musculoskeletal and connective tissue disorders
|
1 Participants
|
1 Participants
|
2 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Respiratory, thoracic and mediastinal disorders
|
0 Participants
|
2 Participants
|
2 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Renal and urinary disorders
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Vascular disorders
|
2 Participants
|
1 Participants
|
2 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Immune system disorders
|
1 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Eye disorders
|
1 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Ear and labyrinth disorders
|
2 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Reproductive system and breast disorders
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Cardiac disorders
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Endocrine disorders
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Surgical and medical procedures
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
|
Surgery Group: Number of Participants With Adverse Events
Neoplasms benign, malignant and unspecified
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
Adverse Events
Everolimus 10 mg + Surgery
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Everolimus 5 mg + Surgery
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Everolimus 0 mg + Surgery
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
No Surgery (Everolimus 10 mg)
Serious events: 6 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Everolimus 10 mg + Surgery
n=6 participants at risk
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 5 mg + Surgery
n=5 participants at risk
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 0 mg + Surgery
n=6 participants at risk
Participants scheduled to undergo salvage surgical resection, received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
No Surgery (Everolimus 10 mg)
n=24 participants at risk
Participants with recurrent Glioblastoma Multiforme (GBM) not scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus (RAD001) until evidence of disease progression or toxicity.
|
|---|---|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
General disorders
Gait Disturbance
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
8.3%
2/24
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Infections and infestations
Bacterial Diarrhoea
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Infections and infestations
Meningitis
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Infections and infestations
Perirectal Abscess
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Infections and infestations
Pneumocystis Jiroveci Pneumonia
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Infections and infestations
Wound infection Staphylococcal
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Nervous system disorders
Convulsion
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Lethargy
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Nervous system disorders
Neuropathy Peripheral
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Nervous system disorders
Pneumocephalus
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Nervous system disorders
intracranial Hypotension
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Oedema
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
Other adverse events
| Measure |
Everolimus 10 mg + Surgery
n=6 participants at risk
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 5 mg + Surgery
n=5 participants at risk
Participants scheduled to undergo salvage surgical resection, received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
Everolimus 0 mg + Surgery
n=6 participants at risk
Participants scheduled to undergo salvage surgical resection, received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
|
No Surgery (Everolimus 10 mg)
n=24 participants at risk
Participants with recurrent Glioblastoma Multiforme (GBM) not scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus (RAD001) until evidence of disease progression or toxicity.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
50.0%
3/6
|
0.00%
0/5
|
33.3%
2/6
|
4.2%
1/24
|
|
Blood and lymphatic system disorders
Leukopenia
|
33.3%
2/6
|
0.00%
0/5
|
50.0%
3/6
|
25.0%
6/24
|
|
Blood and lymphatic system disorders
Lymph Node Pain
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Blood and lymphatic system disorders
Lymphopenia
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
12.5%
3/24
|
|
Blood and lymphatic system disorders
Neutropenia
|
33.3%
2/6
|
20.0%
1/5
|
33.3%
2/6
|
16.7%
4/24
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
50.0%
3/6
|
20.0%
1/5
|
33.3%
2/6
|
12.5%
3/24
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Ear and labyrinth disorders
Ear Discomfort
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Ear and labyrinth disorders
Hypoacusis
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Ear and labyrinth disorders
Tinnitus
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Endocrine disorders
Cushingoid
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Eye disorders
Vision Blurred
|
16.7%
1/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Gastrointestinal disorders
Aphthous Stomatitis
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Gastrointestinal disorders
Constipation
|
50.0%
3/6
|
80.0%
4/5
|
16.7%
1/6
|
8.3%
2/24
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6
|
20.0%
1/5
|
0.00%
0/6
|
16.7%
4/24
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Gastrointestinal disorders
Frequent Bowel Movements
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Gastrointestinal disorders
Haemorrhoids
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Gastrointestinal disorders
Lip Pain
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Gastrointestinal disorders
Nausea
|
16.7%
1/6
|
0.00%
0/5
|
16.7%
1/6
|
8.3%
2/24
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
12.5%
3/24
|
|
Gastrointestinal disorders
Toothache
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
General disorders
Facial Pain
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
General disorders
Fatigue
|
50.0%
3/6
|
40.0%
2/5
|
33.3%
2/6
|
33.3%
8/24
|
|
General disorders
Irritability
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
8.3%
2/24
|
|
General disorders
Localised Oedema
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
General disorders
Mucosal inflammation
|
33.3%
2/6
|
20.0%
1/5
|
50.0%
3/6
|
4.2%
1/24
|
|
General disorders
Oedema Peripheral
|
33.3%
2/6
|
0.00%
0/5
|
16.7%
1/6
|
8.3%
2/24
|
|
General disorders
Pain
|
0.00%
0/6
|
40.0%
2/5
|
0.00%
0/6
|
4.2%
1/24
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
8.3%
2/24
|
|
Immune system disorders
Drug Hypersensitivity
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Immune system disorders
Seasonal Allergy
|
0.00%
0/6
|
20.0%
1/5
|
16.7%
1/6
|
4.2%
1/24
|
|
Infections and infestations
Fungal Skin infection
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Infections and infestations
Gastroenteritis Viral
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Infections and infestations
Herpes Zoster Oticus
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Infections and infestations
Oral Candidiasis
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Infections and infestations
Oral Herpes
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Infections and infestations
Paronychia
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Infections and infestations
Pneumonia
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Infections and infestations
Respiratory Tract infection
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Infections and infestations
Sinusitis
|
16.7%
1/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Infections and infestations
Upper Respiratory Tract infection
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
4.2%
1/24
|
|
Infections and infestations
Urinary Tract infection
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
12.5%
3/24
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
12.5%
3/24
|
|
Injury, poisoning and procedural complications
Endotracheal intubation Complication
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
8.3%
2/24
|
|
Injury, poisoning and procedural complications
Procedural Pain
|
66.7%
4/6
|
40.0%
2/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Injury, poisoning and procedural complications
Radiation Necrosis
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Injury, poisoning and procedural complications
incision Site Pain
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Investigations
Alanine Aminotransferase increased
|
33.3%
2/6
|
20.0%
1/5
|
16.7%
1/6
|
8.3%
2/24
|
|
Investigations
Aspartate Aminotransferase increased
|
33.3%
2/6
|
0.00%
0/5
|
0.00%
0/6
|
8.3%
2/24
|
|
Investigations
Blood Albumin Decreased
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
8.3%
2/24
|
|
Investigations
Blood Alkaline Phosphatase increased
|
16.7%
1/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Investigations
Blood Bicarbonate Decreased
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Investigations
Blood Cholesterol increased
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
16.7%
4/24
|
|
Investigations
Blood Triglycerides increased
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
16.7%
4/24
|
|
Investigations
Gamma-Glutamyltransferase increased
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Investigations
Haemoglobin Decreased
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Investigations
Heart Rate increased
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Investigations
Low Density Lipoprotein increased
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
12.5%
3/24
|
|
Investigations
Oxygen Saturation Decreased
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Investigations
Platelet Count Decreased
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
12.5%
3/24
|
|
Investigations
Protein Total increased
|
33.3%
2/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Investigations
Weight Decreased
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
12.5%
3/24
|
|
Investigations
Weight increased
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/6
|
20.0%
1/5
|
16.7%
1/6
|
8.3%
2/24
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
8.3%
2/24
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
16.7%
1/6
|
0.00%
0/5
|
16.7%
1/6
|
16.7%
4/24
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
100.0%
6/6
|
40.0%
2/5
|
33.3%
2/6
|
20.8%
5/24
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
16.7%
1/6
|
20.0%
1/5
|
16.7%
1/6
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
16.7%
1/6
|
40.0%
2/5
|
16.7%
1/6
|
12.5%
3/24
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
16.7%
1/6
|
20.0%
1/5
|
33.3%
2/6
|
8.3%
2/24
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
33.3%
2/6
|
0.00%
0/5
|
16.7%
1/6
|
12.5%
3/24
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
33.3%
2/6
|
0.00%
0/5
|
33.3%
2/6
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
16.7%
1/6
|
0.00%
0/5
|
16.7%
1/6
|
12.5%
3/24
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
33.3%
2/6
|
0.00%
0/5
|
33.3%
2/6
|
8.3%
2/24
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
1/6
|
20.0%
1/5
|
16.7%
1/6
|
4.2%
1/24
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
8.3%
2/24
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
8.3%
2/24
|
|
Musculoskeletal and connective tissue disorders
Pain in Jaw
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Amnesia
|
16.7%
1/6
|
0.00%
0/5
|
33.3%
2/6
|
0.00%
0/24
|
|
Nervous system disorders
Aphasia
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Ataxia
|
50.0%
3/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Brain Oedema
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Cognitive Disorder
|
33.3%
2/6
|
20.0%
1/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Nervous system disorders
Depressed Level of Consciousness
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Nervous system disorders
Dizziness
|
33.3%
2/6
|
20.0%
1/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Nervous system disorders
Facial Palsy
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Headache
|
16.7%
1/6
|
40.0%
2/5
|
16.7%
1/6
|
16.7%
4/24
|
|
Nervous system disorders
Hemianopia
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Nervous system disorders
Hypogeusia
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Nervous system disorders
Memory Impairment
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Nervous system disorders
Mental Impairment
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/6
|
40.0%
2/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
50.0%
3/6
|
20.0%
1/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Sinus Headache
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Nervous system disorders
Speech Disorder
|
33.3%
2/6
|
0.00%
0/5
|
16.7%
1/6
|
8.3%
2/24
|
|
Nervous system disorders
Visual Field Defect
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Psychiatric disorders
Anxiety
|
33.3%
2/6
|
20.0%
1/5
|
0.00%
0/6
|
8.3%
2/24
|
|
Psychiatric disorders
Confusional State
|
16.7%
1/6
|
20.0%
1/5
|
16.7%
1/6
|
4.2%
1/24
|
|
Psychiatric disorders
Depression
|
33.3%
2/6
|
20.0%
1/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Psychiatric disorders
Hallucination
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Psychiatric disorders
insomnia
|
33.3%
2/6
|
20.0%
1/5
|
16.7%
1/6
|
12.5%
3/24
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/6
|
0.00%
0/5
|
0.00%
0/6
|
8.3%
2/24
|
|
Renal and urinary disorders
incontinence
|
0.00%
0/6
|
0.00%
0/5
|
33.3%
2/6
|
4.2%
1/24
|
|
Reproductive system and breast disorders
Sexual Dysfunction
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Allergic Cough
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
0.00%
0/24
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6
|
20.0%
1/5
|
16.7%
1/6
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6
|
0.00%
0/5
|
16.7%
1/6
|
4.2%
1/24
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Skin and subcutaneous tissue disorders
Pain of Skin
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
1/6
|
20.0%
1/5
|
0.00%
0/6
|
8.3%
2/24
|
|
Skin and subcutaneous tissue disorders
Rash Erythematous
|
0.00%
0/6
|
20.0%
1/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
|
0.00%
0/6
|
0.00%
0/5
|
33.3%
2/6
|
4.2%
1/24
|
|
Skin and subcutaneous tissue disorders
Rash Papular
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
4.2%
1/24
|
|
Skin and subcutaneous tissue disorders
increased Tendency To Bruise
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Surgical and medical procedures
Tooth Extraction
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/6
|
0.00%
0/5
|
33.3%
2/6
|
0.00%
0/24
|
|
Vascular disorders
Haematoma
|
16.7%
1/6
|
0.00%
0/5
|
0.00%
0/6
|
0.00%
0/24
|
|
Vascular disorders
Hypertension
|
16.7%
1/6
|
20.0%
1/5
|
0.00%
0/6
|
0.00%
0/24
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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; or the publication of the trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER