Study of Everolimus (RAD001) in Patients With Recurrent Glioblastoma Multiforme (GBM)

• Surgery Group: Percentage Change From the Baseline in S6 Kinase Levels [ Time Frame: Baseline and Day 7-9 (during salvage surgery) ] [ Designated as safety issue: No ]
  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.
  
  
• No Surgery Group: Best Overall Tumor Response [ Time Frame: First day of treatment to study discontinuation (up to 60 weeks) ] [ Designated as safety issue: No ]
  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.
  
  

• Surgery Group: Blood and Brain Tissue Levels of Everolimus (RAD001) [ Time Frame: Baseline and Day 7-9 (Blood samples were collected one day prior to surgery and tissue samples were collected during surgery.) ] [ Designated as safety issue: No ]
  
• Surgery Group: Progression-free Survival [ Time Frame: After surgery (within 96 hours), Weeks 4 and 8 and then every 8 weeks after restarting treatment until study discontinuation (Up to 28 weeks) ] [ Designated as safety issue: No ]
  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.
  
  
• Surgery Group: Biomarkers Phosphatase and Tensin Homolog (PTEN) and Epidermal Growth Factor Receptor (EGFR) [ Time Frame: After surgery, week 4, week 8 and every 8 weeks thereafter ] [ Designated as safety issue: No ]

  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.

  
  
• No Surgery Group: Progression Free Survival [ Time Frame: First day of treatment to study discontinuation (up to 60 weeks) ] [ Designated as safety issue: No ]
  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.
  
  
• Surgery Group: Number of Participants With Adverse Events [ Time Frame: First day of treatment to study discontinuation (Up to 28 weeks) ] [ Designated as safety issue: No ]
  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.
  
  

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.