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

Phase 2TerminatedNCT00515086

Novartis Pharmaceuticals41 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Glioblastoma Multiforme

Interventions

EverolimusDRUG

Tablets taken once a day with a full glass of water.

SurgeryPROCEDURE

Salvage surgical resection

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (8)

UCLA

Los Angeles, California, United States

Northwestern University

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Surgery Group: Percentage Change From the Baseline in S6 Kinase Levels

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.

Time frame: Baseline and Day 7-9 (during salvage surgery)

No Surgery Group: Best Overall Tumor Response

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.

Time frame: First day of treatment to study discontinuation (up to 60 weeks)

Secondary Outcomes

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.)

Surgery Group: Progression-free Survival

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.

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)

Surgery Group: Biomarkers Phosphatase and Tensin Homolog (PTEN) and Epidermal Growth Factor Receptor (EGFR)

Data from ClinicalTrials.gov

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