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

NCT00515086 | Terminated Phase 2 Results

• 1 other identifier: CRAD001C2410
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 8

Brief Summary

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

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma Multiforme, GBM, RAD001, RAD

Outcome Measures

Primary Outcomes (2)

• 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 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)

Secondary Outcomes (5)

• 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.)

• Surgery Group: Progression-free Survival

  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)

  After surgery, week 4, week 8 and every 8 weeks thereafter

• No Surgery Group: Progression Free Survival

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

• Surgery Group: Number of Participants With Adverse Events

  First day of treatment to study discontinuation (Up to 28 weeks)

Study Arms (4)

No Surgery (Everolimus 10 mg)

EXPERIMENTAL

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

Everolimus 10 mg + Surgery

EXPERIMENTAL

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; Procedure: Surgery

Everolimus 5 mg + Surgery

EXPERIMENTAL

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; Procedure: Surgery

Everolimus 0 mg + Surgery

ACTIVE COMPARATOR

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; Procedure: Surgery

Interventions

Everolimus DRUG

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

Also known as: RAD001

Everolimus 0 mg + Surgery; Everolimus 10 mg + Surgery; Everolimus 5 mg + Surgery; No Surgery (Everolimus 10 mg)

Surgery PROCEDURE

Salvage surgical resection

Everolimus 0 mg + Surgery; Everolimus 10 mg + Surgery; Everolimus 5 mg + Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (8)

UCLA

Los Angeles, California, 90095, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Duke University - Preston Robert Tisch Brain Tumor Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Glioblastoma; Dyschromatosis symmetrica hereditaria 1

Interventions

Everolimus; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Due to the early termination of this study, the analysis of some of the planned objectives is not included in this clinical study report.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2007
• First Posted: August 13, 2007
• Study Start: August 1, 2007
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: September 22, 2011
• Results First Posted: July 27, 2011

Record last verified: 2011-09

Locations

US (8)