Glioblastoma MultiformePhase 2NCT00515086
Study of Everolimus (RAD001) in Patients With Recurrent Glioblastoma Multiforme (GBM)
A Phase 2 study testing Everolimus and Surgery in people with Glioblastoma Multiforme, run by Novartis Pharmaceuticals at 8 sites in United States.
Trial summary
This study will define the safety and efficacy of Everolimus (RAD001) administered daily in patients with glioblastoma multiforme (GBM) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Everolimus and Surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 8 sitesUnited States
- Study dates
- Aug 2007to Aug 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Northwestern University
Chicago, Illinois, 60611
University of Cincinnati
Cincinnati, Ohio, 45219
Duke University - Preston Robert Tisch Brain Tumor Center
Durham, North Carolina, 27710
UCLA
Los Angeles, California, 90095
Seattle Cancer Care Alliance
Seattle, Washington, 98109
About this study
Official title: 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)
Read the 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.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Everolimus, Surgery
- Keywords
- Glioblastoma Multiforme, GBM, RAD001, RAD
- Medical subject headings
- Glioblastoma, Dyschromatosis symmetrica hereditaria 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called RAD001
Tablets taken once a day with a full glass of water.
SurgeryProcedure or surgery
Salvage surgical resection
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Everolimus; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: First day of treatment to study discontinuation (up to 60 weeks)
Secondary outcomes (5)
Surgery Group: Blood and Brain Tissue Levels of Everolimus (RAD001)
Measured: 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.
Measured: 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)
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.
Measured: After surgery, week 4, week 8 and every 8 weeks thereafter
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.
Measured: First day of treatment to study discontinuation (up to 60 weeks)
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.
Measured: First day of treatment to study discontinuation (Up to 28 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionAug 2009
- Study completionAug 2009
Why it stopped: Early termination due to slow enrollment and protocol-defined stopping rule.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00515086
- Sponsor's protocol ID
- CRAD001C2410
- Status last verified
- Sep 2011
- First submitted
- 10 Aug 2007
- Last updated
- 22 Sep 2011
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of RAD001 in Patients With Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00515086
- Acronym / sponsor ID
- CRAD001C2410
- Conditions
- Glioblastoma Multiforme
- Keywords
- Glioblastoma Multiforme, GBM, RAD001, RAD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early termination due to slow enrollment and protocol-defined stopping rule.
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Aug 2007
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 13 Aug 2007 (estimated)
- Results
- Posted 27 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will define the safety and efficacy of Everolimus (RAD001) administered daily in patients with glioblastoma multiforme (GBM)
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| No Surgery (Everolimus 10 mg) | Experimental | Drug: EverolimusParticipants 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. |
| Everolimus 10 mg + Surgery | Experimental | Drug: Everolimus, Procedure: SurgeryParticipants 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. |
| Everolimus 5 mg + Surgery | Experimental | Drug: Everolimus, Procedure: SurgeryParticipants 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. |
| Everolimus 0 mg + Surgery | Active comparator | Drug: Everolimus, Procedure: SurgeryParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: RAD001Tablets taken once a day with a full glass of water. | Drug | Everolimus 0 mg + Surgery, Everolimus 10 mg + Surgery, Everolimus 5 mg + Surgery, No Surgery (Everolimus 10 mg) |
| SurgerySalvage surgical resection | Procedure or surgery | Everolimus 0 mg + Surgery, Everolimus 10 mg + Surgery, Everolimus 5 mg + Surgery |
Primary outcome
Surgery Group: Percentage Change From the Baseline in S6 Kinase Levels
Time frame: Baseline and Day 7-9 (during salvage surgery)
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)
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.
5 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
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)
Time frame: After surgery, week 4, week 8 and every 8 weeks thereafter
No Surgery Group: Progression Free Survival
Time frame: First day of treatment to study discontinuation (up to 60 weeks)
Surgery Group: Number of Participants With Adverse Events
Time frame: First day of treatment to study discontinuation (Up to 28 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus and Surgery in people with Glioblastoma Multiforme, run by Novartis Pharmaceuticals at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Surgery Group: Percentage Change From the Baseline in S6 Kinase Levels (time frame: Baseline and Day 7-9 (during salvage surgery)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2011.