Radiation Therapy and Temsirolimus or Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma

NCT ID: NCT01019434

Last Updated: 2018-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2014-03-31

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether radiation therapy is more effective when given together with temsirolimus or temozolomide in treating patients with glioblastoma.

PURPOSE: This randomized phase II trial is studying giving radiation therapy together with temsirolimus to see how well it works compared with giving radiation therapy together with temozolomide in treating patients with newly diagnosed glioblastoma.

Detailed Description

OBJECTIVES:

Primary

• Document the activity profile of temsirolimus by the evaluation of overall survival at 1 year in patients with newly diagnosed glioblastoma multiforme, without methylation of the MGMT gene promoter, treated with temsirolimus before and concomitantly with radiotherapy, followed by temsirolimus maintenance therapy.

Secondary

• Investigate safety and tolerability of this therapy regimen in these patients.
• Assess progression-free survival and overall survival of these patients.
• Assess biomarkers in the tumor tissue relevant to temsirolimus and disease state, and their correlation to clinical outcome in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to institution, age in years (< 50 vs ≥ 50), Karnofsky performance status (PS) (< 80% vs ≥ 80%) OR ECOG PS (0 or 1 vs 2), and corticosteroid use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Within 7 weeks after surgery or open biopsy, patients undergo radiotherapy 5 days a week for 6 weeks and receive oral temozolomide concurrently once daily for 6 weeks. Beginning 4 weeks after completion of concurrent chemoradiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression and unacceptable toxicity.
• Arm II: Within 7 weeks after surgery or open biopsy, patients undergo radiotherapy 5 days a week for 6 weeks. Patients also receive temsirolimus IV over 30-60 minutes once weekly beginning 7 days before initiation of radiotherapy. After completion of chemoradiotherapy, patients receive maintenance temsirolimus IV once weekly in the absence of disease progression and unacceptable toxicity.

Frozen tumor biopsies or paraffin-embedded tumor material obtained from surgery or open biopsy and blood samples are collected for analysis of molecular markers, determination of the methylation status of the MGMT gene promoter (before randomization and at a later time), and other studies.

After completion of study therapy, patients are followed every 3 months.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Temozolomide

TMZ will be given at 75 mg/m2 daily for the whole period of RT including weekends as registered.

Group Type: OTHER

temozolomide

Intervention Type: DRUG

TMZ will be given at 75 mg/m2 daily for the whole period of RT including weekends as registered.

Temsirolimus

CCI-779 will be given i.v. once every week at 25 mg. Each treatment should be preceded by supportive medication with a histamine H2-receptor antagonist. A first dose of CCI-779, being 25 mg, will be given on day -7 from RT start.

Group Type: EXPERIMENTAL

temsirolimus

Intervention Type: DRUG

CCI-779 will be given i.v. once every week at 25 mg. Each treatment should be preceded by supportive medication with a histamine H2-receptor antagonist. A first dose of CCI-779, being 25 mg, will be given on day -7 from RT start.

Interventions

temozolomide

TMZ will be given at 75 mg/m2 daily for the whole period of RT including weekends as registered.

Intervention Type: DRUG

temsirolimus

CCI-779 will be given i.v. once every week at 25 mg. Each treatment should be preceded by supportive medication with a histamine H2-receptor antagonist. A first dose of CCI-779, being 25 mg, will be given on day -7 from RT start.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• No known hypersensitivity to the study treatment
• No known hypersensitivity to antihistamines or other medical reason that prohibits the intake of antihistamines
• No current alcohol dependence or drug abuse
• No legal incapacity or limited legal capacity
• Able to undergo a gadolinium-enhanced MRI of the brain

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior and no concurrent investigational agent
• No prior stereotactic biopsy
• At least 30 days since prior drug therapy that has not received regulatory approval for any indication
• No chemotherapy within the past 5 years
• No prior chemotherapy for a brain tumor
• No prior radiotherapy to the head
• No other concurrent anticancer therapy
• No concurrent anticoagulation therapy except low-dose prophylactic low molecular weight heparin
• Concurrent steroid therapy allowed provided patient is on a stable or decreasing dose for ≥ 1 week
• At least 14 days since prior and no concurrent enzyme-inducing anticonvulsants (e.g., carbamazepine, phenobarbital, and phenytoin)
• No concurrent strong inducers or inhibitors of CYP3A4
• No concurrent planned surgery for other diseases (e.g., dental extraction)
• No placement of Gliadel® wafer during prior surgery

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wolfgang Wick

Role: STUDY_CHAIR

Universitatsklinikum Heidelberg

Gianfranco Pesce, MD

Role: STUDY_CHAIR

Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

Locations

UZ Leuven

Leuven, , Belgium

Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau

Nantes-Saint Herblain, , France

CHU Pitie-Salpetriere AP-HP

Paris, , France

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Ospedale Bellaria

Bologna, , Italy

Erasmus MC - Daniel den Hoed Cancer Center

Rotterdam, , Netherlands

Medisch Centrum Haaglanden - Westeinde

The Hague, , Netherlands

ICO Badalona - Hospital Germans Trias i Pujol

Badalona, , Spain

Ospedale Regionale Bellinzona e Valli

Bellinzona, , Switzerland

UniversitaetsSpital Zuerich

Zurich, , Switzerland

Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, United Kingdom

Western General Hospital

Edinburgh, , United Kingdom

Countries

Belgium; France; Germany; Italy; Netherlands; Spain; Switzerland; United Kingdom

Other Identifiers

EORTC-26082

Identifier Type: -

Identifier Source: secondary_id

EORTC-22081

Identifier Type: -

Identifier Source: secondary_id

EU-20987

Identifier Type: -

Identifier Source: secondary_id

2008-003003-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC-26082-22081

Identifier Type: -

Identifier Source: org_study_id