Trial Outcomes & Findings for Everolimus in Treating Patients With Recurrent Low-Grade Glioma (NCT NCT00823459)

Last Updated: 2020-07-28

Results Overview

Number of patients alive without progressive disease at 6 months. Assessment of progression was defined by RANO as a 25% increase in the sum of all the products of measurable lesions, clear worsening of any evaluable disease or any new lesion

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

At 6 months after treatment start

Results posted on

2020-07-28

Participant Flow

Participant milestones

Participant milestones
Measure	Daily Intervention With RAD001 Single arm study: RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food.
Overall Study STARTED	58
Overall Study COMPLETED	58
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Everolimus in Treating Patients With Recurrent Low-Grade Glioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daily Intervention With RAD001 n=58 Participants RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	55 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	50 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: At 6 months after treatment start

Population: All patients treated with study drug

Outcome measures

Outcome measures
Measure	Daily Intervention With RAD001 n=58 Participants RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food. RAD001: RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food.
Progression-free Survival at 6 Months. Grade II	39 Participants
Progression-free Survival at 6 Months. Grade III/IV	6 Participants

SECONDARY outcome

Timeframe: 13 months

Population: All patients treated from the time of registration until discontinuation of study drug

Grade 4-5 treatment related adverse events as defined by CTCAE 3.0

Outcome measures

Outcome measures
Measure	Daily Intervention With RAD001 n=58 Participants RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food. RAD001: RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food.
RAD001 Safety Profile in Patients With Recurrent LLG	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: All patients who were treated with study drug

Objective response is defined as complete or partial response as defined by RANO criteria as determined by MRI and steroid requirement. Complete response was defined by disappearance of all measurable disease with minimal or no steroids; a partial response was defined as 50% in sum of all products in perpendicular diameters of all measurable lesions with no new lesions on stable or decreasing steroids.

Outcome measures

Outcome measures
Measure	Daily Intervention With RAD001 n=58 Participants RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food. RAD001: RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food.
Objective Response Rate (ORR) in Patients Treated With RAD001.	0 participants

SECONDARY outcome

Timeframe: Time from registration till death, an average of 5 years

Population: All patients in study

Number of years from the day the patient started treatment until the date of death, an average of 5 years.

Outcome measures

Outcome measures
Measure	Daily Intervention With RAD001 n=58 Participants RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food. RAD001: RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food.
Overall Survival (OS) in Patients Treated With RAD001.	5.2 years Interval 4.0 to Upper limit of confidence interval not reached due to insufficient number of patients with events

SECONDARY outcome

Timeframe: 5 years

Population: Patients for which the molecular marker PI3K pathway activation was available

Survival of patients with p-S6 staining of \>19% (activated pathway)

Outcome measures

Outcome measures
Measure	Daily Intervention With RAD001 n=50 Participants RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food. RAD001: RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food.
To Assess the Correlation of Activation of the PI3K/mTOR Pathway With Survival	3.9 years Interval 3.4 to Upper bound not reached

Adverse Events

Daily Intervention With RAD001

Serious events: 6 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Daily Intervention With RAD001 n=58 participants at risk RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.4% 2/58 • Number of events 2 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders Seizure	3.4% 2/58 • Number of events 2 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
General disorders Fever	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders Pain	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Infections and infestations Infection	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Renal and urinary disorders Renal/Genitourinary	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy

Other adverse events

Other adverse events
Measure	Daily Intervention With RAD001 n=58 participants at risk RAD001 will be administered orally as once daily dose of 10 mg (two 5 mg tablets) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day. RAD001 may be taken with or without food.
Nervous system disorders Mood Alteration	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders Neuropathy	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders Speech Impairment	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders Syncope	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders Pain	10.3% 6/58 • Number of events 12 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Gastrointestinal disorders Pain	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Renal and urinary disorders Renal/Genitourinary	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Gastrointestinal disorders Diarrhea	24.1% 14/58 • Number of events 33 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Gastrointestinal disorders Nausea	12.1% 7/58 • Number of events 8 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Gastrointestinal disorders constipation	6.9% 4/58 • Number of events 4 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Gastrointestinal disorders vomiting	3.4% 2/58 • Number of events 2 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Gastrointestinal disorders mucositis/stomatitis	5.2% 3/58 • Number of events 9 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Gastrointestinal disorders mucosititis/stomatitis	3.4% 2/58 • Number of events 2 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Gastrointestinal disorders Flatulence	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders seizure	8.6% 5/58 • Number of events 6 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders ataxia	3.4% 2/58 • Number of events 2 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders Dizzness	3.4% 2/58 • Number of events 2 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders neuropathy	3.4% 2/58 • Number of events 2 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Nervous system disorders mood alteration	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Musculoskeletal and connective tissue disorders Pain	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Respiratory, thoracic and mediastinal disorders Pain	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Infections and infestations Infection	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
General disorders Fatigue	8.6% 5/58 • Number of events 9 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
General disorders insomnia	3.4% 2/58 • Number of events 3 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
General disorders Fever	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Skin and subcutaneous tissue disorders Pruritus	8.6% 5/58 • Number of events 6 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Skin and subcutaneous tissue disorders Rash	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Musculoskeletal and connective tissue disorders Muscle weakness	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Musculoskeletal and connective tissue disorders Musculoskeletal/soft Tissue	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Respiratory, thoracic and mediastinal disorders Cough	8.6% 5/58 • Number of events 6 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Respiratory, thoracic and mediastinal disorders Dyspnea	5.2% 3/58 • Number of events 3 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.4% 2/58 • Number of events 3 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Eye disorders Blurred vision	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Blood and lymphatic system disorders lymphopenia	5.2% 3/58 • Number of events 5 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Blood and lymphatic system disorders Leukocytes	3.4% 2/58 • Number of events 12 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Blood and lymphatic system disorders Platelets	3.4% 2/58 • Number of events 6 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Blood and lymphatic system disorders Neutrophils	3.4% 2/58 • Number of events 3 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Metabolism and nutrition disorders Increased ALT	3.4% 2/58 • Number of events 3 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Metabolism and nutrition disorders hypertriglyceridemia	10.3% 6/58 • Number of events 16 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Metabolism and nutrition disorders Hypophosephatemia	6.9% 4/58 • Number of events 4 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Metabolism and nutrition disorders Hypercholesteremia	5.2% 3/58 • Number of events 5 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Metabolism and nutrition disorders Hyperglycemia	5.2% 3/58 • Number of events 4 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Metabolism and nutrition disorders Hyperkalemia	1.7% 1/58 • Number of events 1 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Metabolism and nutrition disorders Hypernatremia	1.7% 1/58 • Number of events 4 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy
Metabolism and nutrition disorders ALT	3.4% 2/58 • Number of events 3 • Time of study start with first day of study dosing until patient is removed from protocol treatment up to 12 months of therapy

Additional Information

Susan Chang, MD

University of California, San Francisco

Phone: (415) 353-2966

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place