Radiation Therapy With and Without Combination Chemotherapy in Patients With Resected Anaplastic Oligodendroglioma

NCT00002840 | Completed Phase 3

• 2 other identifiers: EORTC-26951MRC-BR11
• Study Type: interventional
• Target: 350
• Locations: 12 countries
• Sites: 40

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells, and may be an effective treatment for anaplastic oligodendroglioma. Combining combination chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Randomized phase III trial to compare radiation therapy with and without combination chemotherapy in patients with resected anaplastic oligodendroglioma.

Conditions

Brain and Central Nervous System Tumors

Keywords

recurrent adult brain tumor; adult anaplastic oligodendroglioma; adult mixed glioma

Interventions

lomustine DRUG

procarbazine hydrochloride DRUG

vincristine sulfate DRUG

radiation therapy RADIATION

Eligibility Criteria

• Age: 16 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: Newly diagnosed oligodendroglioma or oligoastrocytoma (with at least 25% oligodendral elements) Low-grade oligodendroastrocytoma or oligodendroglioma that is recurrent after surgery without radiotherapy is allowed Prior partial or gross total resection of tumor (or biopsy only in case of no further surgical option) required At least 3 of the following histologic anaplastic features: High cellularity Endothelial abnormalities Nuclear abnormalities Necrosis Mitoses PATIENT CHARACTERISTICS: Age: 16 to 69 Performance status: ECOG 0-2 Life expectancy: At least 3 months Hematopoietic: WBC at least 3,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.4 mg/dL Renal: Creatinine no greater than 1.3 mg/dL Creatinine clearance at least 60 mL/min Other: Not pregnant or nursing Fertile patients must use effective contraception No active or uncontrolled infection No other disease, including malignancy, that would preclude study No neurologic or psychiatric disturbance that would preclude study PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics No prior radiotherapy to the skull Surgery: See Disease Characteristics

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
• Medical Research Council: collaborator

Study Sites (40)

Kaiser Franz Josef Hospital

Vienna (Wien), A-1100, Austria

Location

Hopital Universitaire Erasme

Brussels, 1070, Belgium

Location

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels (Bruxelles), 1090, Belgium

Location

Hopital de Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

Turku University Central Hospital

Turku, FIN-2-0521, Finland

Location

Centre Hospitalier Regional de Lille

Lille, 59037, France

Location

CHU de la Timone

Marseille, 13385, France

Location

CHU de Nancy - Hopital Neurologique

Nancy, 54035, France

Location

CRLCC Nantes - Atlantique

Nantes-Saint Herblain, 44805, France

Location

Hopital Pasteur

Nice, 06002, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

C.H.R. de Nimes - Hopital Caremeau

Nîmes, 30000, France

Location

CHU Pitie-Salpetriere

Paris, 75651, France

Location

Centre Eugene Marquis

Rennes, 35064, France

Location

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Neurologische Klinik der Henriettenstiftung

Hanover, D-30559, Germany

Location

Klinikum der Friedrich-Schiller Universitaet Jena

Jena, D-07740, Germany

Location

National Institute of Neurosurgery

Budapest, 1145, Hungary

Location

Azienda Ospedaliera di Padova

Padova (Padua), 35128, Italy

Location

Universita di Padova

Padua, 35128, Italy

Location

Medisch Centrum Haaglanden

's-Gravenhage (Den Haag, the Hague), 2501 CK, Netherlands

Location

Vrije Universiteit Medisch Centrum

Amsterdam, 1001HV, Netherlands

Location

Academisch Medisch Centrum

Amsterdam, 1105 AZ, Netherlands

Location

Academisch Ziekenhuis Groningen

Groningen, 9713 EZ, Netherlands

Location

University Medical Center Nijmegen

Nijmegen, NL-6500 HB, Netherlands

Location

Rotterdam Cancer Institute

Rotterdam, 3075 EA, Netherlands

Location

St. Elisabeth Ziekenhuis

Tilburg, 5022 GC, Netherlands

Location

Dr. Bernard Verbeeten Instituut

Tilburg, 5042 SB, Netherlands

Location

Academisch Ziekenhuis Utrecht

Utrecht, 3584 CX, Netherlands

Location

Instituto Portugues de Oncologia de Francisco Gentil

Lisbon, 1093, Portugal

Location

University Hospital of Linkoping

Linköping, S-581 85, Sweden

Location

Umea Universitet

Umeå, S-901 85, Sweden

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, CH-1011, Switzerland

Location

Nottingham General Hospital

Nottingham, England, NG1 6HA, United Kingdom

Location

Nottingham City Hospital NHS Trust

Nottingham, England, NG5 1PB, United Kingdom

Location

Queen's Medical Centre

Nottingham, England, NG7 2UH, United Kingdom

Location

Royal South Hants Hospital

Southampton, England, SO14 0YG, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Royal Marsden Hospital

Sutton, England, SM2 5PT, United Kingdom

Location

Related Publications (15)

• Idbaih A, Dalmasso C, Kouwenhoven M, Jeuken J, Carpentier C, Gorlia T, Kros JM, French P, Teepen J, Broet P, Delattre O, Mokhtari K, Sanson M, Delattre JY, van den Bent M, Hoang-Xuan K. Genomic aberrations associated with outcome in anaplastic oligodendroglial tumors treated within the EORTC phase III trial 26951. J Neurooncol. 2011 Jun;103(2):221-30. doi: 10.1007/s11060-010-0380-9. Epub 2010 Sep 6.

  PMID: 20820870 RESULT

• Mokhtari K, Ducray F, Kros JM, Gorlia T, Idbaih A, Taphoorn M, Wesseling P, Hoang-Xuan K, Van den Bent M, Sanson M. Alpha-internexin expression predicts outcome in anaplastic oligodendroglial tumors and may positively impact the efficacy of chemotherapy: European organization for research and treatment of cancer trial 26951. Cancer. 2011 Jul 1;117(13):3014-26. doi: 10.1002/cncr.25827. Epub 2011 Jan 18.

  PMID: 21246521 RESULT

• van den Bent MJ, Gravendeel LA, Gorlia T, Kros JM, Lapre L, Wesseling P, Teepen JL, Idbaih A, Sanson M, Smitt PA, French PJ. A hypermethylated phenotype is a better predictor of survival than MGMT methylation in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951. Clin Cancer Res. 2011 Nov 15;17(22):7148-55. doi: 10.1158/1078-0432.CCR-11-1274. Epub 2011 Sep 13.

  PMID: 21914791 RESULT

• Preusser M, Hoeftberger R, Woehrer A, et al.: Prognostic value and analytical performance (reproducibility) of Ki67 index in anaplastic oligodendroglial tumors: A translational study of the EORTC Brain Tumor Group. [Abstract] J Clin Oncol 28 (Suppl 15): A-2029, 2010.

  RESULT

• van den Bent MJ, Dubbink HJ, Marie Y, Brandes AA, Taphoorn MJ, Wesseling P, Frenay M, Tijssen CC, Lacombe D, Idbaih A, van Marion R, Kros JM, Dinjens WN, Gorlia T, Sanson M. IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group. Clin Cancer Res. 2010 Mar 1;16(5):1597-604. doi: 10.1158/1078-0432.CCR-09-2902. Epub 2010 Feb 16.

  PMID: 20160062 RESULT

• Kouwenhoven MC, Gorlia T, Kros JM, Ibdaih A, Brandes AA, Bromberg JE, Mokhtari K, van Duinen SG, Teepen JL, Wesseling P, Vandenbos F, Grisold W, Sipos L, Mirimanoff R, Vecht CJ, Allgeier A, Lacombe D, van den Bent MJ. Molecular analysis of anaplastic oligodendroglial tumors in a prospective randomized study: A report from EORTC study 26951. Neuro Oncol. 2009 Dec;11(6):737-46. doi: 10.1215/15228517-2009-011.

  PMID: 19224764 RESULT

• van den Bent MJ, Dubbink HJ, Sanson M, van der Lee-Haarloo CR, Hegi M, Jeuken JW, Ibdaih A, Brandes AA, Taphoorn MJ, Frenay M, Lacombe D, Gorlia T, Dinjens WN, Kros JM. MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951. J Clin Oncol. 2009 Dec 10;27(35):5881-6. doi: 10.1200/JCO.2009.24.1034. Epub 2009 Nov 9.

  PMID: 19901104 RESULT

• Kros JM, Gorlia T, Kouwenhoven MC, Zheng PP, Collins VP, Figarella-Branger D, Giangaspero F, Giannini C, Mokhtari K, Mork SJ, Paetau A, Reifenberger G, van den Bent MJ. Panel review of anaplastic oligodendroglioma from European Organization For Research and Treatment of Cancer Trial 26951: assessment of consensus in diagnosis, influence of 1p/19q loss, and correlations with outcome. J Neuropathol Exp Neurol. 2007 Jun;66(6):545-51. doi: 10.1097/01.jnen.0000263869.84188.72.

  PMID: 17549014 RESULT

• Mauer ME, Taphoorn MJ, Bottomley A, Coens C, Efficace F, Sanson M, Brandes AA, van der Rijt CC, Bernsen HJ, Frenay M, Tijssen CC, Lacombe D, van den Bent MJ; EORTC Brain Cancer Group. Prognostic value of health-related quality-of-life data in predicting survival in patients with anaplastic oligodendrogliomas, from a phase III EORTC brain cancer group study. J Clin Oncol. 2007 Dec 20;25(36):5731-7. doi: 10.1200/JCO.2007.11.1476.

  PMID: 18089867 RESULT

• Taphoorn MJ, van den Bent MJ, Mauer ME, Coens C, Delattre JY, Brandes AA, Sillevis Smitt PA, Bernsen HJ, Frenay M, Tijssen CC, Lacombe D, Allgeier A, Bottomley A; European Organisation for Research and Treatment of Cancer. Health-related quality of life in patients treated for anaplastic oligodendroglioma with adjuvant chemotherapy: results of a European Organisation for Research and Treatment of Cancer randomized clinical trial. J Clin Oncol. 2007 Dec 20;25(36):5723-30. doi: 10.1200/JCO.2007.12.7514.

  PMID: 18089866 RESULT

• van den Bent MJ, Carpentier AF, Brandes AA, Sanson M, Taphoorn MJ, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Haaxma-Reiche H, Kros JM, van Kouwenhoven MC, Vecht CJ, Allgeier A, Lacombe D, Gorlia T. Adjuvant procarbazine, lomustine, and vincristine improves progression-free survival but not overall survival in newly diagnosed anaplastic oligodendrogliomas and oligoastrocytomas: a randomized European Organisation for Research and Treatment of Cancer phase III trial. J Clin Oncol. 2006 Jun 20;24(18):2715-22. doi: 10.1200/JCO.2005.04.6078.

  PMID: 16782911 RESULT

• van den Bent MJ, Delattre JY, Brandes AA, et al.: First analysis of EORTC trial 26951, a randomized phase III study of adjuvant PCV chemotherapy in patients with highly anaplastic oligodendroglioma. [Abstract] J Clin Oncol 23 (Suppl 16): A-1503, 114s, 2005.

  RESULT

• Lassman AB, Hoang-Xuan K, Polley MC, Brandes AA, Cairncross JG, Kros JM, Ashby LS, Taphoorn MJB, Souhami L, Dinjens WNM, Laack NN, Kouwenhoven MCM, Fink KL, French PJ, Macdonald DR, Lacombe D, Won M, Gorlia T, Mehta MP, van den Bent MJ. Joint Final Report of EORTC 26951 and RTOG 9402: Phase III Trials With Procarbazine, Lomustine, and Vincristine Chemotherapy for Anaplastic Oligodendroglial Tumors. J Clin Oncol. 2022 Aug 10;40(23):2539-2545. doi: 10.1200/JCO.21.02543. Epub 2022 Jun 22.

  PMID: 35731991 DERIVED

• Erdem-Eraslan L, Gravendeel LA, de Rooi J, Eilers PH, Idbaih A, Spliet WG, den Dunnen WF, Teepen JL, Wesseling P, Sillevis Smitt PA, Kros JM, Gorlia T, van den Bent MJ, French PJ. Intrinsic molecular subtypes of glioma are prognostic and predict benefit from adjuvant procarbazine, lomustine, and vincristine chemotherapy in combination with other prognostic factors in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951. J Clin Oncol. 2013 Jan 20;31(3):328-36. doi: 10.1200/JCO.2012.44.1444. Epub 2012 Dec 26.

  PMID: 23269986 DERIVED

• van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Enting RH, French PJ, Dinjens WN, Vecht CJ, Allgeier A, Lacombe D, Gorlia T, Hoang-Xuan K. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol. 2013 Jan 20;31(3):344-50. doi: 10.1200/JCO.2012.43.2229. Epub 2012 Oct 15.

  PMID: 23071237 DERIVED

MeSH Terms

Conditions

Central Nervous System Neoplasms; Brain Neoplasms; Oligodendroglioma; Glioma

Interventions

Lomustine; Procarbazine; Vincristine; Radiotherapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Benzamides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Therapeutics

Study Officials

• Martin J. van Den Bent, MD

  Daniel Den Hoed Cancer Center at Erasmus Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 22, 2004
• Study Start: August 1, 1996
• Primary Completion: March 1, 2002
• Last Updated: July 10, 2012

Record last verified: 2012-07

Locations

BE (4); FI (1); IT (2); NL (9); SE (2); CH (1); GB (6); AU (1); HU (1); DE (2); PT (1); FR (10)