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

This study has been terminated.
(Early termination due to slow enrollment and protocol-defined stopping rule.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00515086
First received: August 10, 2007
Last updated: September 20, 2011
Last verified: September 2011

August 10, 2007
September 20, 2011
August 2007
August 2009   (final data collection date for primary outcome measure)
  • 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.
Not Provided
Complete list of historical versions of study NCT00515086 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
Not Provided
 
Study of Everolimus (RAD001) in Patients With Recurrent Glioblastoma Multiforme (GBM)
A Phase II Trial of RAD001 in Patients With Recurrent Glioblastoma Multiforme

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Glioblastoma Multiforme
  • Drug: Everolimus
    Tablets taken once a day with a full glass of water.
    Other Name: RAD001
  • Procedure: Surgery
    Salvage surgical resection
  • Experimental: No Surgery (Everolimus 10 mg)
    Participants with recurrent Glioblastoma Multiforme (GBM) not scheduled to undergo salvage surgical resection, received a daily oral dose of 10 mg Everolimus (RAD001) until evidence of disease progression or toxicity.
    Intervention: Drug: Everolimus
  • Experimental: Everolimus 10 mg + Surgery
    Participants scheduled to undergo salvage surgical resection received a daily oral dose of 10 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
    Interventions:
    • Drug: Everolimus
    • Procedure: Surgery
  • Experimental: Everolimus 5 mg + Surgery
    Participants scheduled to undergo salvage surgical resection received a daily oral dose of 5 mg Everolimus for 7 days prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
    Interventions:
    • Drug: Everolimus
    • Procedure: Surgery
  • Active Comparator: Everolimus 0 mg + Surgery
    Participants scheduled to undergo salvage surgical resection received no treatment with Everolimus prior to surgery, then after recovery from surgery received a 10 mg daily oral dose of Everolimus until evidence of disease progression or toxicity.
    Interventions:
    • Drug: Everolimus
    • Procedure: Surgery
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
41
August 2009
August 2009   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00515086
CRAD001C2410
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
September 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP