Radiation Therapy or Temozolomide in Treating Patients With Gliomas

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Primary Chemotherapy With Temozolomide Versus Radiotherapy in Patients With Low Grade Gliomas After Stratification for Genetic 1p Loss: A Phase III Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00182819
• Other study ID #: EORTC-22033-26033
• Secondary ID: 2004-002714-11CA
• Status: Completed
• Phase: Phase 3
• First received: September 15, 2005
• Last updated: October 11, 2016
• Start date: July 2005
• Est. completion date: May 2014

Study information

• Verified date: October 2016
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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 than temozolomide in treating gliomas.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared to temozolomide in treating patients with gliomas.

Description:

OBJECTIVES:

Primary

• Compare the progression-free survival of patients with low-grade gliomas treated with radiotherapy vs temozolomide.

Secondary

• Compare the overall survival of patients treated with these regimens.

• Determine whether the incidence of late toxicity can be decreased in patients who are randomized to receive temozolomide.

• Compare the toxic effects of these regimens in these patients.

• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, chromosome 1p status (deleted vs normal vs undeterminable), contrast enhancement on MRI (yes vs no), age (< 40 years vs ≥ 40 years), and WHO performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo radiotherapy once daily, 5 days a week, for a total of 28 fractions (i.e., 5½ weeks).

• Arm II: Patients receive oral temozolomide once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then every 3 months until disease progression.

After completion of study treatment, patients are followed every 6 months for survival.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A minimum of 699 patients (a total of 466 randomized [233 per treatment arm]) will be accrued for this study within 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 709
• Est. completion date: May 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed low-grade glioma, including any of the following types:

• Astrocytoma (gemistocytic, fibrillary, or protoplasmatic)

• Oligoastrocytoma

• Oligodendroglioma

• WHO grade II disease

• Supratentorial tumor location only

• RTOG neurological function 0-3

• Not a candidate for surgical treatment alone

• Requires treatment, as determined by = 1 of the following criteria:

• Age = 40 years

• Radiologically-proven progressive lesion

• New or worsening neurological symptoms other than seizures only (e.g., focal deficits, signs of increased intracranial pressure, or mental deficits)

• Intractable seizures, defined by both of the following criteria:

• Experiences persistent seizures that interfere with everyday life activities except driving a car

• Failed 3 anti-epileptic drug regimens, including = 1 combination regimen

• Tumor material (paraffin-embedded) or histopathologic slides available

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

Hepatic

• No chronic hepatitis B or C infection

• Bilirubin = 1.5 times upper limit of normal (ULN)

• AST or ALT = 2.5 times ULN

• Alkaline phosphatase = 2.5 times ULN

Renal

• Creatinine = 1.5 times ULN

Other

• Not pregnant or nursing

• Fertile patients must use effective contraception during and for 6 months after completion of study treatment

• No known HIV positivity

• No other serious medical condition

• No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer

• No psychological, familial, sociological, or geographical condition that would preclude study participation

• No medical condition that would preclude receiving oral medication (e.g., frequent vomiting or partial bowel obstruction)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent growth factors for elevating absolute neutrophil counts for the purpose of temozolomide administration

• No concurrent epoetin alfa

• No concurrent immunotherapy or biologic therapy

Chemotherapy

• No prior chemotherapy

• No other concurrent chemotherapy, including adjuvant chemotherapy for patients randomized to undergo radiotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the brain

• No concurrent integrated boost with intensity-modulated radiotherapy

Surgery

• Recovered from prior surgery

• No concurrent surgical tumor debulking

Other

• No prior randomization to this study

• No other concurrent investigational drugs

• No concurrent regular use of agents known to be radiosensitizers or radioprotectors (e.g., cyclooxygenase-2 inhibitors, thalidomide, or amifostine) during study radiotherapy

• Occasional use of nonsteroidal anti-inflammatory drugs for pain allowed

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioma
• Nervous System Neoplasms

Intervention

Drug:
• temozolomide
Temozolomide 75 mg/m2 daily x 21 days, q 28 days until progression or for max. 12 cycles

Radiation:
• radiation therapy
50.4 Gy, standard fractionation (28 x 1.8 Gy), conformal techniques

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
Australia	Austin and Repatriation Medical Centre	Heidelberg West	Victoria
Australia	Liverpool Hospital	Liverpool
Australia	Sir Charles Gairdner Hospital - Nedlands	Nedlands	Western Australia
Australia	Alfred Hospital	Prahran	Victoria
Australia	Prince of Wales Private Hospital	Randwick	New South Wales
Australia	Mater Adult Hospital	South Brisbane	Queensland
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Australia	Sydney Cancer Centre at Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Austria	Medical University Vienna - General Hospital AKH	Vienna
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Universitair Ziekenhuis Brussel	Brussels
Belgium	U.Z. Leuven - Campus Gasthuisberg	Leuven
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Nova Scotia Cancer Centre	Halifax	Nova Scotia
Canada	Margaret and Charles Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Hopital Notre-Dame du CHUM	Montreal	Quebec
Canada	Mcgill University Health Centre - Gerald Bronfman Centre - Dept Of Oncology	Montreal	Quebec
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Edmond Odette Cancer Centre at Sunnybrook	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	BC Cancer Agency	Vancouver
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Egypt	National Cancer Institute of Egypt	Cairo
France	CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre	Bordeaux
France	Institut Bergonie	Bordeaux
France	CHU de Grenoble - Hopital de la Tronche	Grenoble
France	CHU de la Timone	Marseille
France	Centre Regional Rene Gauducheau	Nantes-Saint Herblain
France	Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere	Paris
France	Centre Eugene Marquis	Rennes
France	Centre Paul Strauss	Strasbourg
France	Institut Claudius Regaud	Toulouse
France	Gustave Roussy	Villejuif
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Universitaetskliniken Regensburg	Regensburg
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Hungary	National Institute Of Neurosurgery	Budapest
Israel	Rambam Health Care Campus, Oncology Institute	Haifa
Italy	Ospedale Bellaria	Bologna
Italy	Ospedale San Raffaele	Milano
Italy	Istituto Regina Elena / Istituti Fisioterapici Ospitalieri	Roma
Italy	Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino	Turin
Luxembourg	Centre Francois Baclesse	Esch / Alzette
Netherlands	Academisch Medisch Centrum - Universiteit van Amsterdam	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Medisch Centrum Haaglanden - Westeinde	Den Haag
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Maastro Clinic - Maastricht Radiation Oncology	Maastricht
Netherlands	Radboud University Medical Center Nijmegen	Nijmegen
Netherlands	Erasmus MC Cancer Institute - location Daniel den Hoed	Rotterdam
Netherlands	Dr. Bernard Verbeeten Instituut	Tilburg
New Zealand	Canterbury Health Laboratories	Christchurch
Portugal	Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, SA	Lisbon
Singapore	National University of Singapore	Singapore
Spain	ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)	Badalona - (Barcelona)
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Clinico Universitario de Barcelona	Barcelona
Spain	Hospital General Vall D'Hebron	Barcelona
Spain	ICO Girona - Hospital Doctor Josep Trueta (Institut Catala D'Oncologia)	Girona
Spain	ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)	L'Hospitalet de Llobregat
Sweden	University Hospital of Linkoping	Linkoping
Sweden	Skane University Hospital	Lund
Sweden	Umea Universitet	Umea
Sweden	Uppsala University Hospital	Uppsala
Switzerland	Oncology Institute of Southern Switzerland - Ospedale Regionale Bellinzona e Valli	Bellinzona
Switzerland	Centre Hospitalier Universitaire Vaudois - Lausanne	Lausanne
Switzerland	UniversitaetsSpital Zurich	Zurich
United Kingdom	Clatterbridge Centre for Oncology	Bebington, Wirral	England
United Kingdom	University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre	Bristol	Avon
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Gloucestershire Hospital NHS Foundation Trust - Cheltenham General Hospital	Cheltenham
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Royal Free Hospital	London
United Kingdom	Royal Marsden - London	London	England
United Kingdom	University College Hospital	London	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Oxford University Hospitals NHS Trust - Churchill Hospital	Oxford
United Kingdom	Lancashire Teaching Hospitals NHS Foundation Trust - Royal Preston Hospital	Preston
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Royal Marsden - Surrey	Sutton	England

Sponsors (4)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	British Medical Research Council, NCIC Clinical Trials Group, Trans-Tasman Radiation Oncology Group (TROG)

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Canada,  Egypt,  France,  Germany,  Hungary,  Israel,  Italy,  Luxembourg,  Netherlands,  New Zealand,  Portugal,  Singapore,  Spain,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (2)

Fairchild A, Weber DC, Bar-Deroma R, Gulyban A, Fenton PA, Stupp R, Baumert BG. Quality assurance in the EORTC 22033-26033/CE5 phase III randomized trial for low grade glioma: the digital individual case review. Radiother Oncol. 2012 Jun;103(3):287-92. doi: 10.1016/j.radonc.2012.04.002. Epub 2012 May 3. — View Citation

Musat E, Roelofs E, Bar-Deroma R, Fenton P, Gulyban A, Collette L, Stupp R, Weber DC, Bernard Davis J, Aird E, Baumert BG. Dummy run and conformity indices in the ongoing EORTC low-grade glioma trial 22033-26033: First evaluation of quality of radiotherapy planning. Radiother Oncol. 2010 May;95(2):218-24. doi: 10.1016/j.radonc.2010.03.005. Epub 2010 Apr 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		5 years	No
Secondary	Overall survival		5 years	No
Secondary	Quality of life as measured by QLQ-C30 v3.0 and EORTC BN-20		every 3 months until progression, and then every 6 months until death	No
Secondary	Mini-Mental State Examination		every 3 months until progression, and then every 6 months until death	No
Secondary	Adverse events as measured by CTCAE v3.0		As indicated in the protocol	Yes