Clinical trial NCT00515086: Study of Everolimus (RAD001) in Patients With Recurrent Glioblastoma Multiforme (GBM)
Official title: A Phase II Trial of RAD001 in Patients With Recurrent Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma Multiforme, GBM, RAD001, RAD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-08-13
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will define the safety and efficacy of Everolimus (RAD001) administered daily in patients with glioblastoma multiforme (GBM)

Detailed description: This was a multicenter, open label, randomized study of RAD001 dosed daily in patients with recurrent GBM. The study was conducted with 2 parallel groups of patients. Group 1 was designed to study the biological effects of RAD001 in patients scheduled to undergo salvage surgical resection, and Group 2 was to enroll patients who were not scheduled for surgery. Patients in Group 1 were randomly assigned to one of three pre-surgery treatment groups (0, 5 or 10 mg/day RAD001 for 7 days). All patients in Group 2 were to receive a fixed daily dose of 10 mg/day oral RAD001.

Eligibility criteria: Inclusion Criteria:

* Age 18 years of age or older
* Histologically confirmed Glioblastoma Multiforme (GBM)
* Radiographic evidence of disease progression
* Patients must have evaluable contrast enhancing tumor
* Availability of paraffin blocks or unstained pathology slides for biomarker studies
* Karnofsky Performance Status of greater than or equal to 60%

Exclusion Criteria:

* Prior treatment with Mammalian target of rapamycin (mTOR) inhibitor
* History of another malignancy within 3 years
* Cardiac pacemaker
* Ferromagnetic metal implants other than those approves as safe for use in Magnetic resonance imaging (MRI) scanners
* Claustrophobia
* Obesity
* Unstable systemic diseases
* Elevated cholesterol or triglycerides
* Radiation therapy or cytotoxic chemotherapy \<=4 weeks prior to study enrollment. Patient must have recovered from the toxic effects of a prior chemotherapy.
* Patients must be off all enzyme inducing anticonvulsants for at least 2 week before study enrollment can occur
* Need for increasing dose of steroids. Patients on a stable or tapering dose of steroids \>=7 days were permitted.

Primary outcomes:
measure: Surgery Group: Percentage Change From the Baseline in S6 Kinase Levels
timeFrame: Baseline and Day 7-9 (during salvage surgery)
measure: No Surgery Group: Best Overall Tumor Response
timeFrame: First day of treatment to study discontinuation (up to 60 weeks)
Secondary outcomes:
measure: Surgery Group: Blood and Brain Tissue Levels of Everolimus (RAD001)
timeFrame: Baseline and Day 7-9 (Blood samples were collected one day prior to surgery and tissue samples were collected during surgery.)
measure: Surgery Group: Progression-free Survival
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)
measure: Surgery Group: Biomarkers Phosphatase and Tensin Homolog (PTEN) and Epidermal Growth Factor Receptor (EGFR)
timeFrame: After surgery, week 4, week 8 and every 8 weeks thereafter
measure: No Surgery Group: Progression Free Survival
timeFrame: First day of treatment to study discontinuation (up to 60 weeks)
measure: Surgery Group: Number of Participants With Adverse Events
timeFrame: First day of treatment to study discontinuation (Up to 28 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Durham
country: United States
facility: Duke University - Preston Robert Tisch Brain Tumor Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: