Clinical trial NCT00020839: Temozolomide With or Without Radiation Therapy to the Brain in Treating Patients With Stage IV Melanoma That Is Metastatic to the Brain
Official title: Temozolomide Versus Temozolomide + Whole Brain Radiation In Stage IV Melanoma Patients With Asymptomatic Brain Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Melanoma (Skin)
Metastatic Cancer
Keywords: stage IV melanoma
recurrent melanoma
tumors metastatic to brain
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

Eligibility 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

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