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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

PHASE III STUDY OF ADJUVANT PROCARBAZINE, CCNU AND VINCRISTINE CHEMOTHERAPY IN PATIENTS WITH HIGHLY ANAPLASTIC OLIGODENDROGLIOMA

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002840
• Other study ID #: EORTC-26951
• Secondary ID: EORTC-26951MRC-B
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: July 6, 2012
• Start date: August 1996

Study information

• Verified date: July 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES: I. Compare survival and time to first progression in patients with anaplastic oligodendroglioma treated with radiotherapy with or without adjuvant procarbazine, lomustine, and vincristine (PCV) following surgical resection. II. Investigate the effect of PCV on quality of life and neurologic function in these patients. III. Determine the toxicity of PCV in these patients. IV. Correlate chromosomal lesions (1p and/or 19q, 9p, p53 loss and mutation, amplification of chromosome 7, or loss of chromosome 10) with progression-free and overall survival in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age, extent of resection, performance status, prior surgery, and participating center. Patients are randomized to one of two treatment arms. Arm I: Within 4-6 weeks after surgery, patients undergo radiotherapy over 7 weeks to the residual tumor volume. Arm II: Patients undergo radiotherapy as in arm I, then begin chemotherapy within 4 weeks after the completion of radiotherapy. Patients receive oral lomustine on day 1, oral procarbazine on days 8-21, and vincristine IV on days 8 and 29. Treatment repeats every 6 weeks in stable and responding patients for a total of 6 courses. Patients with disease recurrence may receive 6 additional courses of chemotherapy as above or another modality at the investigator's discretion. Patients are followed every 3 months for 1 year and then every 6 months for survival.

PROJECTED ACCRUAL: A total of 350 patients will be accrued for this study within 4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 350
• Est. primary completion date: March 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 69 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• lomustine

• procarbazine hydrochloride

• vincristine sulfate

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Austria	Kaiser Franz Josef Hospital	Vienna (Wien)
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels (Bruxelles)
Belgium	Hopital de Jolimont	Haine Saint Paul
Belgium	U.Z. Gasthuisberg	Leuven
Finland	Turku University Central Hospital	Turku
France	Centre Hospitalier Regional de Lille	Lille
France	CHU de la Timone	Marseille
France	CHU de Nancy - Hopital Neurologique	Nancy
France	CRLCC Nantes - Atlantique	Nantes-Saint Herblain
France	Centre Antoine Lacassagne	Nice
France	Hopital Pasteur	Nice
France	C.H.R. de Nimes - Hopital Caremeau	Nimes
France	CHU Pitie-Salpetriere	Paris
France	Centre Eugene Marquis	Rennes
France	Institut Gustave Roussy	Villejuif
Germany	Neurologische Klinik der Henriettenstiftung	Hannover
Germany	Klinikum der Friedrich-Schiller Universitaet Jena	Jena
Hungary	National Institute of Neurosurgery	Budapest
Italy	Universita di Padova	Padova
Italy	Azienda Ospedaliera di Padova	Padova (Padua)
Netherlands	Medisch Centrum Haaglanden	's-Gravenhage (Den Haag, The Hague)
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Rotterdam Cancer Institute	Rotterdam
Netherlands	Dr. Bernard Verbeeten Instituut	Tilburg
Netherlands	St. Elisabeth Ziekenhuis	Tilburg
Netherlands	Academisch Ziekenhuis Utrecht	Utrecht
Portugal	Instituto Portugues de Oncologia de Francisco Gentil	Lisbon
Sweden	University Hospital of Linkoping	Linkoping
Sweden	Umea Universitet	Umea
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United Kingdom	Nottingham City Hospital NHS Trust	Nottingham	England
United Kingdom	Nottingham General Hospital	Nottingham	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Royal South Hants Hospital	Southampton	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden Hospital	Sutton	England

Sponsors (2)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC	Medical Research Council

Countries where clinical trial is conducted

Austria,  Belgium,  Finland,  France,  Germany,  Hungary,  Italy,  Netherlands,  Portugal,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (12)

Idbaih A, Dalmasso C, Kouwenhoven M, Jeuken J, Carpentier C, Gorlia T, Kros JM, French P, Teepen J, Broët P, Delattre O, Mokhtari K, Sanson M, Delattre JY, van den Bent M, Hoang-Xuan K. Genomic aberrations associated with outcome in anaplastic oligodendro — View Citation

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 olig — View Citation

Kros JM, Gorlia T, Kouwenhoven MC, Zheng PP, Collins VP, Figarella-Branger D, Giangaspero F, Giannini C, Mokhtari K, Mørk SJ, Paetau A, Reifenberger G, van den Bent MJ. Panel review of anaplastic oligodendroglioma from European Organization For Research a — View Citation

Mauer ME, Taphoorn MJ, Bottomley A, Coens C, Efficace F, Sanson M, Brandes AA, van der Rijt CC, Bernsen HJ, Frénay M, Tijssen CC, Lacombe D, van den Bent MJ; EORTC Brain Cancer Group. Prognostic value of health-related quality-of-life data in predicting s — View Citation

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: — View Citation

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

Taphoorn MJ, van den Bent MJ, Mauer ME, Coens C, Delattre JY, Brandes AA, Sillevis Smitt PA, Bernsen HJ, Frénay M, Tijssen CC, Lacombe D, Allgeier A, Bottomley A; European Organisation for Research and Treatment of Cancer. Health-related quality of life i — View Citation

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 vincris — View Citation

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, 200

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 anaplast — View Citation

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 — View Citation

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 — View Citation

* Note: There are 12 references in all — Click here to view all references