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

Glioblastoma Multiforme Clinical Trial

Official title:

A Phase II Trial of RAD001 in Patients With Recurrent Glioblastoma Multiforme

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00515086
• Other study ID #: CRAD001C2410
• Status: Terminated
• Phase: Phase 2
• First received: August 10, 2007
• Last updated: September 20, 2011
• Start date: August 2007
• Est. completion date: August 2009

Study information

• Verified date: September 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: August 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• Everolimus
Tablets taken once a day with a full glass of water.

Procedure:
• Surgery
Salvage surgical resection

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Duke University - Preston Robert Tisch Brain Tumor Center	Durham	North Carolina
United States	UCLA	Los Angeles	California
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and Day 7-9 (during salvage surgery)	No
Primary	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.	First day of treatment to study discontinuation (up to 60 weeks)	No
Secondary	Surgery Group: Blood and Brain Tissue Levels of Everolimus (RAD001)		Baseline and Day 7-9 (Blood samples were collected one day prior to surgery and tissue samples were collected during surgery.)	No
Secondary	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.	After surgery (within 96 hours), Weeks 4 and 8 and then every 8 weeks after restarting treatment until study discontinuation (Up to 28 weeks)	No
Secondary	Surgery Group: Biomarkers Phosphatase and Tensin Homolog (PTEN) and Epidermal Growth Factor Receptor (EGFR)	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.	After surgery, week 4, week 8 and every 8 weeks thereafter	No
Secondary	No 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 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.	First day of treatment to study discontinuation (up to 60 weeks)	No
Secondary	Surgery Group: Number of Participants With Adverse Events	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.	First day of treatment to study discontinuation (Up to 28 weeks)	No