Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Radiation Therapy With or Without Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 to 70		EORTC-26981 CAN-NCIC-CE3, EORTC-22981, NCT00006353, CE3

Objectives

I.  Compare the efficacy of radiotherapy with or without temozolomide in terms 
of overall survival in patients with newly diagnosed glioblastoma multiforme.

II.  Compare the toxicity profiles of these regimens in these patients.

III.  Compare the progression free survival of these patients treated with 
these regimens.

IV.  Compare the quality of life in these patients treated with these regimens.

Entry Criteria

Disease Characteristics:

Histologically confirmed newly diagnosed glioblastoma multiforme by biopsy or
surgical resection
 Grade IV disease
 Initial diagnosis no greater than 6 weeks prior to study

Prior/Concurrent Therapy:

Biologic therapy:
 No concurrent filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa
 No concurrent biologic therapy
 No concurrent immunotherapy

Chemotherapy:
 No prior chemotherapy
 No other concurrent chemotherapy

Endocrine therapy:
 At least 14 days of prior corticosteroids at a stable dose required
 Concurrent corticosteroids allowed

Radiotherapy:
 No prior radiotherapy
 No concurrent stereotactic boost radiotherapy

Surgery:
 See Disease Characteristics
 No concurrent surgery for tumor debulking

Other:
 No other concurrent investigational drugs

Patient Characteristics:

Age:
 18 to 70

Performance status:
 WHO 0-2

Life expectancy:
 Not specified

Hematopoietic:
 Absolute neutrophil count at least 1,500/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin no greater than 1.5 times upper limit of normal (ULN)
 AST or ALT less than 2.5 times ULN
 Alkaline phosphatase less than 2.5 times ULN
 No chronic hepatitis B or C 

Renal:
 Creatinine no greater than 1.5 times ULN

Other:
 Not pregnant or nursing
 Negative pregnancy test
 Fertile patients must use effective contraception
 No known HIV infection
 No medical condition that would interfere with oral medication intake (e.g.,
  frequent vomiting or partial bowel obstruction)
 No other prior or concurrent malignancy except surgically cured carcinoma in
  situ of the cervix or nonmelanoma skin cancer
 No serious medical, psychological, familial, sociological, or geographical
  condition that would preclude study

Expected Enrollment

A total of 520 patients (260 per treatment arm) will be accrued for this study 
within 3.5 years.

Outline

This is a randomized, multicenter study.  Patients are stratified according to 
participating center, age (under 50 vs 50 and over), WHO/ECOG performance 
status (0-1 vs 2), and extent of surgical resection (biopsy only vs complete 
or incomplete resection).  Patients are randomized to one of two treatment 
arms.

Arm I:  Patients undergo radiotherapy 5 days a week for 6 weeks.

Arm II:  Patients undergo radiotherapy as in arm I concurrently with oral 
temozolomide daily for 6 weeks.  Patients then receive adjuvant oral 
temozolomide alone on days 1-5 every 28 days for 6 courses beginning 4 weeks 
after completion of radiotherapy.

Quality of life is assessed prior to the study, at week 4 during radiotherapy, 
at 4 weeks after completion of radiotherapy, at the end of courses 3 and 6 of 
adjuvant chemotherapy (arm II), and then every 3 months until disease 
progression.

Patients are followed every 3 months until disease progression or death.

Stupp R, Hegi ME, Mason WP, et al.: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol : , 2009.[PUBMED Abstract]

Gorlia T, van den Bent MJ, Hegi ME, et al.: Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. Lancet Oncol 9 (1): 29-38, 2008.[PUBMED Abstract]

Mauer M, Stupp R, Taphoorn MJ, et al.: The prognostic value of health-related quality-of-life data in predicting survival in glioblastoma cancer patients: results from an international randomised phase III EORTC Brain Tumour and Radiation Oncology Groups, and NCIC Clinical Trials Group study. Br J Cancer 97 (3): 302-7, 2007.[PUBMED Abstract]

Mirimanoff R, Mason W, van den Bent M, et al.: Is long-term survival in glioblastoma possible? Updated results of the EORTC/NCIC phase III randomized trial on radiotherapy (RT) and concomitant and adjuvant temozolomide (TMZ) versus RT alone. [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): Plenary-3, S2, 2007.

Mirimanoff RO, Gorlia T, Mason W, et al.: Radiotherapy and temozolomide for newly diagnosed glioblastoma: recursive partitioning analysis of the EORTC 26981/22981-NCIC CE3 phase III randomized trial. J Clin Oncol 24 (16): 2563-9, 2006.[PUBMED Abstract]

Bottomley A, Taphoorn M, Coens C, et al.: Predicting survival using health related quality of life scores in glioblastoma cancers: findings from an international phase III randomised controlled trial. [Abstract] J Clin Oncol 23 (Suppl 16): A-9601, 861s, 2005.

Cohen MH, Johnson JR, Pazdur R: Food and Drug Administration Drug approval summary: temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme. Clin Cancer Res 11 (19 Pt 1): 6767-71, 2005.[PUBMED Abstract]

Hegi ME, Diserens AC, Gorlia T, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352 (10): 997-1003, 2005.[PUBMED Abstract]

Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005.[PUBMED Abstract]

Taphoorn MJ, Stupp R, Coens C, et al.: Health-related quality of life in patients with glioblastoma: a randomised controlled trial. Lancet Oncol 6 (12): 937-44, 2005.[PUBMED Abstract]

Ataman F, Poortmans P, Stupp R, et al.: Quality assurance of the EORTC 26981/22981; NCIC CE3 intergroup trial on radiotherapy with or without temozolomide for newly-diagnosed glioblastoma multiforme: the individual case review. Eur J Cancer 40 (11): 1724-30, 2004.[PUBMED Abstract]

Gorlia T, Stupp R, Eisenhauer EA, et al.: Clinical prognostic factors affecting survival in patients with newly diagnosed glioblastoma multiforme (GBM). [Abstract] J Clin Oncol 22 (Suppl 14): A-9599, 859s, 2004.

Hegi M, Diserens A, Hamou M, et al.: Temozolomide (TMZ) targets only glioblastoma with a silenced MGMT-gene. Results of a translational companion study to EORTC 26981/NCIC CE.3 or radiotherapy ± TMZ. [Abstract] Eur J Cancer 2 (8 Suppl 2): A-31, 14, 2004.

Mirimanoff RO, Mason W, Kortmann R, et al.: Radiotherapy (RT) and concomitant and adjuvant temozolomide (TMZ) versus radiotherapy alone for newly diagnosed glioblastoma (GBM): overall results and recursive partitioning analysis (RPA) of a phase III randomized trial of the EORTC Brain Tumor and Radiotherapy Group and the NCIC Clinical Trial Group. [Abstract] Int J Radiat Oncol Biol Phys 60 (1 Suppl 1): A-55, S162, 2004. Available online. Last accessed January 26, 2005.

Murat A, Migliavacca E, Shay T, et al.: Gene expression profiling of human glioblastoma. A translational research study to the randomized trial EORTC 26981/NCIC CE.3 testing radiotherapy ± temozolomide. [Abstract] Eur J Cancer 2 (Suppl 8): A- 654, 197, 2004.

Stupp R, Mason WP, Van Den Bent MJ, et al.: Concomitant and adjuvant temozolomide (TMZ) and radiotherapy (RT) for newly diagnosed glioblastoma multiforme (GBM). Conclusive results of a randomized phase III trial by the EORTC Brain & RT Groups and NCIC Clinical Trials Group. [Abstract] J Clin Oncol 22 (Suppl 14): A-2, 1s, 2004.

Taphoorn MJ, Stupp R, Osoba D, et al.: An international phase III, randomized, controlled trial evaluating health-related quality of life in glioblastoma patients. [Abstract] Neuro-Oncology 6 (4): A-QL-13, 348, 2004.

Taphoorn MJ, Stupp R, Osoba D, et al.: Joint EORTC brain tumour group/radiotherapy group and NCIC CTG phase III randomized controlled trial evaluating health-related quality of life in glioblastoma patients . [Abstract] Ann Oncol 15 (3): A-7810, 2004.

Lamers LM, Stupp R, van den Bent MJ, et al.: Cost-effectiveness of temozolomide for the treatment of newly diagnosed glioblastoma multiforme: a report from the EORTC 26981/22981 NCI-C CE3 Intergroup Study. Cancer 112 (6): 1337-44, 2008.[PUBMED Abstract]

Mason WP, Cairncross JG: Drug Insight: temozolomide as a treatment for malignant glioma--impact of a recent trial. Nat Clin Pract Neurol 1 (2): 88-95, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Roger Stupp, MD, Protocol chair		Ph: 41-21-314-0156 Email: roger.stupp@chuv.ch

European Organization for Research and Treatment of Cancer

Volker Budach, MD, PhD, Protocol chair		Ph: 49-30-450-52-7021 Email: volker.budach@charite.de

NCIC-Clinical Trials Group

J. Gregory Cairncross, MD, Protocol chair(Contact information may not be current)		Ph: 519-685-8615

Registry Information
Official Title		Concomitant and Adjuvant Temozolomide and Radiotherapy for Newly Diagnosed Glioblastoma Multiforme - A Randomized Phase III Study
Trial Start Date		2000-07-24
Registered in ClinicalTrials.gov		NCT00006353
Date Submitted to PDQ		2000-08-16
Information Last Verified		2009-03-24