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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT01019434
First received: November 24, 2009
Last updated: October 2, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: temozolomide
Drug: temsirolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Radiation Therapy and Concurrent Plus Adjuvant Temsirolimus (CCI-779) Versus Chemo-Irradiation With Temozolomide in Newly Diagnosed Glioblastoma Without Methylation of the MGMT Gene Promoter - A Randomized Multicenter, Open-Label, Phase II Study.

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Overall survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentages of worst Adverse Events or Laboratory Event grades as measured by CTCAEs Version 4.0 criteria [ Time Frame: end of trial ] [ Designated as safety issue: Yes ]
  • Progression-free survival (PFS) probability at 6 months and at 12 months, and overall survival (OS) probability at 2 years [ Time Frame: end of trial ] [ Designated as safety issue: No ]
  • Correlation between biomarkers relevant to temsirolimus and PFS and OS [ Time Frame: end of trial ] [ Designated as safety issue: No ]

Estimated Enrollment: 108
Study Start Date: October 2009
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Temozolomide
TMZ will be given at 75 mg/m2 daily for the whole period of RT including weekends as registered.
Drug: temozolomide
TMZ will be given at 75 mg/m2 daily for the whole period of RT including weekends as registered.
Experimental: 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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01019434

Locations
Austria
Medical University Vienna - General Hospital
Vienna, Austria, AT 1090
Belgium
UZ Leuven
Leuven, Belgium
France
Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau
Nantes-Saint Herblain, France, 44805
CHU Pitie-Salpetriere AP-HP
Paris, France, FR 75651
Germany
Universitaetsklinikum Freiburg
Freiburg, Germany, DE 79106
Universitatsklinikum Heidelberg
Heidelberg, Germany, D-69120
Italy
Ospedale Bellaria
Bologna, Italy, I-40139
Netherlands
Medisch Centrum Haaglanden - Westeinde
Den Haag, Netherlands, NL 2501
Erasmus MC - Daniel den Hoed Cancer Center
Rotterdam, Netherlands, NL 3008
Spain
ICO Badalona - Hospital Germans Trias i Pujol
Badalona, Spain, ES 08916
Switzerland
Ospedale Regionale Bellinzona e Valli
Bellinzona, Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland, CH 1011
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
United Kingdom
Bristol Haematology and Oncology Centre
Bristol, England, United Kingdom, BS2 8ED
Clatterbridge Cancer Centre NHS Foundation Trust
Bebington, Wirral, United Kingdom
Western General Hospital
Edinburgh, United Kingdom
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Pfizer
Investigators
Study Chair: Wolfgang Wick Universitatsklinikum Heidelberg
Study Chair: Gianfranco Pesce, MD Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
  More Information

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT01019434     History of Changes
Other Study ID Numbers: EORTC-26082-22081, EORTC-26082, EORTC-22081, EU-20987, 2008-003003-31
Study First Received: November 24, 2009
Last Updated: October 2, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adult glioblastoma

Additional relevant MeSH terms:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Histamine H2 Antagonists
Sirolimus
Everolimus
Temozolomide
Dacarbazine
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 29, 2014