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

NCT ID: NCT00020839

Last Updated: 2012-09-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-04-30

Brief 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.

Detailed 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.

Conditions

Melanoma (Skin); Metastatic Cancer

Keywords

stage IV melanoma; recurrent melanoma; tumors metastatic to brain

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

temozolomide

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Juergen C. Becker, MD, PhD

Role: STUDY_CHAIR

Universitaets-Hautklinik Wuerzburg

Locations

Krankenhaus der Elisabethinen

Linz, , Austria

Institut Jules Bordet

Brussels, , Belgium

Hopital Universitaire Erasme

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Clinique Notre Dame de Grace

Gosselies, , Belgium

Onkologicka Klinka A Onkologicka Lab

Prague, , Czechia

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, , France

Universitaetsklinikum Benjamin Franklin

Berlin, , Germany

Federal Armed Forces Hospital of Ulm - Department of Dermatology

Blaustein, , Germany

Universitaets - Augenklinik - Erlangen

Erlangen, , Germany

Georg August Universitaet

Göttingen, , Germany

Haematologisch-Onkologische Praxis Altona

Hamburg, , Germany

III Medizinische Klinik Mannheim

Mannheim, , Germany

Eberhard Karls Universitaet

Tübingen, , Germany

Universitaet Wuerzburg/Hautkrankheiten

Würzburg, , Germany

Istituto Nazionale per la Ricerca sul Cancro

Genoa (Genova), , Italy

University Medical Center Nijmegen

Nijmegen, , Netherlands

Erasmus University Medical Center

Rotterdam, , Netherlands

Norwegian Radium Hospital

Oslo, , Norway

Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa

Lisbon, , Portugal

UniversitaetsSpital

Zurich, , Switzerland

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, United Kingdom

Countries

Austria; Belgium; Czechia; France; Germany; Italy; Netherlands; Norway; Portugal; Switzerland; United Kingdom

Other Identifiers

EORTC-18981

Identifier Type: -

Identifier Source: secondary_id

EORTC-18981

Identifier Type: -

Identifier Source: org_study_id