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
  Purpose

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


Condition Intervention Phase
Glioblastoma Multiforme
Drug: Everolimus
Procedure: Surgery
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of RAD001 in Patients With Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 41
Study Start Date: August 2007
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Everolimus
Tablets taken once a day with a full glass of water.
Other Name: RAD001
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.
Drug: Everolimus
Tablets taken once a day with a full glass of water.
Other Name: RAD001
Procedure: Surgery
Salvage surgical resection
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.
Drug: Everolimus
Tablets taken once a day with a full glass of water.
Other Name: RAD001
Procedure: Surgery
Salvage surgical resection
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.
Drug: Everolimus
Tablets taken once a day with a full glass of water.
Other Name: RAD001
Procedure: Surgery
Salvage surgical resection

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00515086

Locations
United States, California
UCLA
Los Angeles, California, United States, 90095
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke University - Preston Robert Tisch Brain Tumor Center
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00515086     History of Changes
Other Study ID Numbers: CRAD001C2410
Study First Received: August 10, 2007
Results First Received: December 15, 2010
Last Updated: September 20, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Glioblastoma Multiforme, GBM, RAD001, RAD

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 28, 2014