Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known whether giving temozolomide during and/or after radiation therapy is more effective than radiation therapy alone in treating anaplastic glioma.

PURPOSE: This randomized phase III trial is studying giving temozolomide during and/or after radiation therapy to see how well it works compared to radiation therapy alone in treating patients with anaplastic glioma.

Further Study Information

OBJECTIVES:

Primary

• To assess whether concurrent radiotherapy with daily temozolomide improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma.

• To assess whether adjuvant temozolomide improves survival as compared to no adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma.

Secondary

• To assess whether concurrent and adjuvant temozolomide prolongs progression-free survival and neurological deterioration-free survival in patients with non-1p/19q deleted anaplastic glioma.

• To assess the safety of concurrent and adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma, including late effects on cognition.

• To assess the impact of concurrent and adjuvant temozolomide on the quality of life of patients with non-1p/19q deleted anaplastic glioma.

OUTLINE: This is a multicenter study. Patients are stratified according to institution, WHO performance status (0 vs > 0), age (≤ 50 vs > 50), presence of 1p LOH only (yes vs no), presence of oligodendroglial elements (yes vs no), and O6-methylguanine-DNA methyltransferase promoter methylation status (methylated vs unmethylated vs indeterminate). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients undergo radiotherapy* once daily, 5 days a week, for 6.5 weeks (total of 33 fractions).

• Arm II: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy).

• Arm III: Patients undergo radiotherapy* once daily, 5 days a week for 6.5 weeks (total of 33 fractions). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.

• Arm IV: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.

NOTE: *Patients must begin radiotherapy within 8 days after randomization and within 7 weeks after surgery.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of-life questionnaires, including QLQ-C30 version 3, BCM20, and the Mini Mental Status Exam at baseline, 4 weeks after the completion of radiotherapy, and then every 3 months for 5 years.

Tissue samples are collected at baseline for histology review, 1p/19q analysis, methylation status of the O6-methylguanine-DNA methyltransferase promoter, and isocitrate dehydrogenase mutation analysis.

After completion of study treatment, patients are followed every 3 months.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

• Anaplastic oligodendroglioma

• Anaplastic oligoastrocytoma

• Anaplastic astrocytoma

• Newly diagnosed disease

• Prior surgery for a low grade tumor is allowed, provided histological confirmation of an anaplastic tumor is present at the time of progression

• Absence of combined 1p/19q loss

• Tumor material available for central 1p/19q assessment, central O6-methylguanine-DNA methyltransferase promoter methylation status assessment, isocitrate dehydrogenase mutation analysis, and central pathology review

• Patients must be on a stable or decreasing dose of steroids for at least two weeks prior to randomization

PATIENT CHARACTERISTICS:

• WHO performance status 0-2

• ANC ≥ 1.5 x 10^9 cells/L

• Platelet count ≥ 100 x 10^9 cells/L

• Bilirubin < 1.5 x upper limit of normal (ULN)

• Alkaline phosphatase < 2.5 x ULN

• AST and ALT < 2.5 x ULN

• Serum creatinine < 1.5 x ULN

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No known HIV infection or chronic hepatitis B or hepatitis C infection

• No other serious medical condition that would interfere with follow-up

• No medical condition that could interfere with oral medication intake (e.g., frequent vomiting or partial bowel obstruction)

• No other prior malignancies except for any malignancy which was treated with curative intent more than 5 years prior to registration and adequately controlled limited basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix

• No prior or concurrent malignancies at other sites except for surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer

• No psychological, familial, sociological, or geographical condition that would potentially hamper compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior chemotherapy, including carmustine-containing wafers (Gliadel®)

• No prior radiotherapy to the brain

• No concurrent growth factors unless vital for the patient

• No other concurrent investigational treatment

• No other concurrent anticancer agents

Trial Contact Information

Trial Lead Organizations/Sponsors

European Organization for Research and Treatment of Cancer

Wolfgang Wick

Study Chair

Warren P. Mason

Study Chair

Michael A. Vogelbaum

Study Chair

S. Erridge

Study Chair

Anna Nowak

Study Chair

Australia
	Nedlands
	Sir Charles Gairdner Hospital - Nedlands
		Anna Nowak	Ph: 61-8-9346-3841
Canada
Manitoba
	Winnipeg
	CancerCare Manitoba
		David Eisenstat	Ph: 204-787-1169
Germany
	Heidelberg
	Universitatsklinikum Heidelberg
		Contact Person	Ph: 49-6221-566-703
Netherlands
	Rotterdam
	Daniel Den Hoed Cancer Center at Erasmus Medical Center
		Contact Person	Ph: 31-10-704-1415
United Kingdom
England
	Bristol
	Bristol Haematology and Oncology Centre
		Contact Person	Ph: 44-117-928-3074
	Cambridge
	Addenbrooke's Hospital
		Contact Person	Ph: 44-1223-245-151
	Cheltenham
	Gloucestershire Oncology Centre at Cheltenham General Hospital
		Contact Person	Ph: 44-8454-222-222
	Exeter
	Royal Devon and Exeter Hospital
		Contact Person	Ph: 44-1392-411-611
	Leeds
	Leeds Cancer Centre at St. James's University Hospital
		Contact Person	Ph: 44-113-206-6400
	Manchester
	Christie Hospital
		Contact Person	Ph: 44-845-226-3000
	Nottingham
	Nottingham City Hospital
		Contact Person	Ph: 44-115-969-1169
	Plymouth
	Derriford Hospital
		Contact Person	Ph: 44-175-277-7111
	Sheffield
	Cancer Research Centre at Weston Park Hospital
		Contact Person	Ph: 44-114-226-5000
Scotland
	Edinburgh
	Edinburgh Cancer Centre at Western General Hospital
		Contact Person	Ph: 44-131-537-1000

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00626990
Information obtained from ClinicalTrials.gov on December 21, 2011

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