Temozolomide With or Without Radiation Therapy to the Brain in Treating Patients With Stage IV Melanoma That Is Metastatic to the Brain

Metastatic Cancer Clinical Trial

Official title:

Temozolomide Versus Temozolomide + Whole Brain Radiation In Stage IV Melanoma Patients With Asymptomatic Brain Metastases

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00020839
• Other study ID #: EORTC-18981
• Secondary ID: EORTC-18981
• Status: Terminated
• Phase: Phase 3
• First received: July 11, 2001
• Last updated: September 20, 2012
• Start date: April 2001

Study information

• Verified date: September 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: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if chemotherapy is more effective with or without radiation therapy in treating brain metastases.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy with or without radiation therapy to the brain in treating patients who have stage IV melanoma with asymptomatic brain metastases.

Description:

OBJECTIVES:

• Compare the efficacy of temozolomide with or without radiotherapy in terms of overall survival in patients with stage IV melanoma with asymptomatic brain metastases.

• Compare the time to appearance of neurological symptoms in patients treated with these regimens.

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

• Compare the quality of life and quality-adjusted survival of patients treated with these regimens.

• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to LDH levels (less than 225 U/L vs 225 U/L or more), concurrent metastases (visceral vs soft tissue), and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral temozolomide once daily on days 1-5. Treatment continues every 4 weeks for a maximum of 1 year in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive temozolomide as in arm I and whole brain radiotherapy on days 8-12 and 15-19 during the first course of chemotherapy.

Quality of life is assessed before beginning each course and then every 4 weeks after completion of study drug.

Patients are followed every 4 weeks.

PROJECTED ACCRUAL: A total of 250 patients will be accrued for this study within 2 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. primary completion date: May 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed unresectable metastatic melanoma

• Must have asymptomatic brain metastasis that is not amenable to surgery or stereotactic radiosurgery (gamma knife, Linac)

• Must have concurrent visceral/soft tissue metastases

• At least 1 site of measurable disease (not necessarily the brain metastasis)

• Documented evidence of disease progression defined by 1 of the following conditions:

• More than 25% increase in the size of at least 1 measurable lesion

• Appearance of a new lesion

• A significant increase in the size of nonmeasurable disease

• No neurological symptoms, including signs of elevated intracranial pressure

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• Hemoglobin at least 10 g/dL

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)

• SGOT or SGPT less than 3 times ULN

• Alkaline phosphatase less than 3 times ULN

Renal:

• Urea less than 1.5 times ULN

• Creatinine less than 1.5 times ULN

Other:

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

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

• No uncontrolled infection

• HIV negative

• No AIDS-related illness

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior cytokine via isolated limb perfusion for local-regional melanoma allowed

• No other prior cytokine for metastatic melanoma

• No concurrent colony-stimulating factors, including epoetin alfa or filgrastim (G-CSF)

• No other concurrent immunologic or biologic therapy

Chemotherapy:

• Prior chemotherapy via isolated limb perfusion for local-regional melanoma allowed

• No other prior chemotherapy for metastatic melanoma

• No other concurrent chemotherapy

Endocrine therapy:

• Concurrent corticosteroids allowed during radiotherapy (arm II only)

• No concurrent hormonal therapy

Radiotherapy:

• See Disease Characteristics

• No other concurrent radiotherapy

Surgery:

• See Disease Characteristics

• Recovered from the effects of any prior major surgery

Other:

• No other concurrent investigational drugs

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Drug:
• temozolomide

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Austria	Krankenhaus der Elisabethinen	Linz
Belgium	Hopital Universitaire Erasme	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Clinique Notre Dame de Grace	Gosselies
Czech Republic	Onkologicka Klinka A Onkologicka Lab	Prague
France	CHU de Bordeaux - Hopital Pellegrin	Bordeaux
France	CHU Ambroise Pare	Boulogne Billancourt
France	Centre Hospital Regional Universitaire de Limoges	Limoges
France	Hopital L'Archet - 2	Nice
France	Centre Eugene Marquis	Rennes
France	Institut Gustave Roussy	Villejuif
Germany	Universitaetsklinikum Benjamin Franklin	Berlin
Germany	Federal Armed Forces Hospital of Ulm - Department of Dermatology	Blaustein
Germany	Universitaets - Augenklinik - Erlangen	Erlangen
Germany	Georg August Universitaet	Goettingen
Germany	Haematologisch-Onkologische Praxis Altona	Hamburg
Germany	III Medizinische Klinik Mannheim	Mannheim
Germany	Eberhard Karls Universitaet	Tuebingen
Germany	Universitaet Wuerzburg/Hautkrankheiten	Wuerzburg
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genoa (Genova)
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Erasmus University Medical Center	Rotterdam
Norway	Norwegian Radium Hospital	Oslo
Portugal	Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa	Lisbon
Switzerland	UniversitaetsSpital	Zurich
United Kingdom	Addenbrooke's NHS Trust	Cambridge	England
United Kingdom	St. James's Hospital	Leeds	England
United Kingdom	Royal Marsden NHS Trust	London	England
United Kingdom	Christie Hospital N.H.S. Trust	Manchester	England
United Kingdom	Weston Park Hospital	Manchester	England
United Kingdom	Clatterbridge Centre for Oncology NHS Trust	Merseyside	England
United Kingdom	Southend NHS Trust Hospital	Westcliff-On-Sea	England

Sponsors (1)

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

Countries where clinical trial is conducted

Austria,  Belgium,  Czech Republic,  France,  Germany,  Italy,  Netherlands,  Norway,  Portugal,  Switzerland,  United Kingdom,