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

NCT01019434 | Completed Phase 2 DMC

• 5 other identifiers: EORTC-26082-22081EORTC-26082EORTC-22081EU-209872008-003003-31
• Study Type: interventional
• Target: 111
• Locations: 8 countries
• Sites: 13

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma

Outcome Measures

Primary Outcomes (1)

• Overall survival at 1 year

  1 year

Secondary Outcomes (3)

• Percentages of worst Adverse Events or Laboratory Event grades as measured by CTCAEs Version 4.0 criteria

  end of trial

• Progression-free survival (PFS) probability at 6 months and at 12 months, and overall survival (OS) probability at 2 years

  end of trial

• Correlation between biomarkers relevant to temsirolimus and PFS and OS

  end of trial

Study Arms (2)

Temozolomide

OTHER

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

Drug: temozolomide

Temsirolimus

EXPERIMENTAL

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.

Drug: temsirolimus

Interventions

temozolomide DRUG

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

Temozolomide

temsirolimus 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.

Temsirolimus

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed (by open brain biopsy or from a neurosurgical resection of the tumor) supratentorial glioblastoma multiforme (GBM) * WHO grade IV disease * Newly diagnosed disease * Must provide demonstration of an unmethylated MGMT-promoter * At least 2 weeks and no more than 6 weeks since surgery or open biopsy * Tumor tissue specimens (paraffin-embedded and/or frozen) from the GBM surgery or open biopsy must be available for central pathology review, MGMT status determination, and exploratory analysis of PI3-K/Akt/mTOR targets (P70S6K) PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 12 weeks * WBC ≥ 3.0 x 10\^9/L * Absolute neutrophil count ≥ 1.5 x10\^9/L * Platelet count ≥ 75.0 x 10\^9/L * Hemoglobin ≥ 10.0 g/dL * Bilirubin ≤ 1.5 times the upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 x ULN * AST and/or ALT ≤ 2.5 x ULN * Serum creatinine \< 1.5 x ULN * PT and PTT normal * Negative pregnancy test * Not pregnant or nursing * Fertile patients must use highly effective contraception * No ischemic heart disease in the past 6 months * 12-lead ECG normal * No history of stroke * No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule * No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer (with no subsequent evidence of recurrence) * No serious concurrent systemic disorder including any of the following that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol: * Active infection * HIV infection * Cardiac disease * QTc prolongation \> 450/470 msec (males/females) * No patients with a congenital long-QT-syndrome in their own or family medical history, unless eligible at the investigator's discretion * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Pfizer: collaborator

Study Sites (13)

UZ Leuven

Leuven, Belgium

Location

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

Nantes-Saint Herblain, 44805, France

Location

CHU Pitie-Salpetriere AP-HP

Paris, FR 75651, France

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, DE 79106, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, D-69120, Germany

Location

Ospedale Bellaria

Bologna, I-40139, Italy

Location

Erasmus MC - Daniel den Hoed Cancer Center

Rotterdam, NL 3008, Netherlands

Location

Medisch Centrum Haaglanden - Westeinde

The Hague, NL 2501, Netherlands

Location

ICO Badalona - Hospital Germans Trias i Pujol

Badalona, ES 08916, Spain

Location

Ospedale Regionale Bellinzona e Valli

Bellinzona, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, United Kingdom

Location

Western General Hospital

Edinburgh, United Kingdom

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma

Interventions

Temozolomide; temsirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Wolfgang Wick

  Universitatsklinikum Heidelberg

  STUDY CHAIR

• Gianfranco Pesce, MD

  Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: November 24, 2009
• First Posted: November 25, 2009
• Study Start: October 1, 2009
• Primary Completion: December 1, 2013
• Study Completion: March 1, 2014
• Last Updated: July 9, 2018

Record last verified: 2018-07

Locations

NL (2); BE (1); CH (2); ES (1); DE (2); IT (1); FR (2); GB (2)