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

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Terminated

CT.gov ID

NCT00020839

Collaborator

(none)

Enrollment

Locations

0.7

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin) Metastatic Cancer	Drug: temozolomide Radiation: radiation therapy	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2001

Actual Primary Completion Date :

May 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Krankenhaus der Elisabethinen	Linz		Austria	4020
2	Institut Jules Bordet	Brussels		Belgium	1000
3	Hopital Universitaire Erasme	Brussels		Belgium	1070
4	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	B-2650
5	Clinique Notre Dame de Grace	Gosselies		Belgium	6041
6	Onkologicka Klinka A Onkologicka Lab	Prague		Czech Republic	128 08
7	CHU de Bordeaux - Hopital Pellegrin	Bordeaux		France	33076
8	CHU Ambroise Pare	Boulogne Billancourt		France	F-92104
9	Centre Hospital Regional Universitaire de Limoges	Limoges		France	87042
10	Hopital L'Archet - 2	Nice		France	F-06202
11	Centre Eugene Marquis	Rennes		France	35042
12	Institut Gustave Roussy	Villejuif		France	F-94805
13	Universitaetsklinikum Benjamin Franklin	Berlin		Germany	D-12200
14	Federal Armed Forces Hospital of Ulm - Department of Dermatology	Blaustein		Germany	D-89134
15	Universitaets - Augenklinik - Erlangen	Erlangen		Germany	D-91054
16	Georg August Universitaet	Goettingen		Germany	D-37075
17	Haematologisch-Onkologische Praxis Altona	Hamburg		Germany	D-22765
18	III Medizinische Klinik Mannheim	Mannheim		Germany	D-68305
19	Eberhard Karls Universitaet	Tuebingen		Germany	D-72076
20	Universitaet Wuerzburg/Hautkrankheiten	Wuerzburg		Germany	D-97080
21	Istituto Nazionale per la Ricerca sul Cancro	Genoa (Genova)		Italy	16132
22	University Medical Center Nijmegen	Nijmegen		Netherlands	NL-6500 HB
23	Erasmus University Medical Center	Rotterdam		Netherlands	3075 EA
24	Norwegian Radium Hospital	Oslo		Norway	N-0310
25	Instituto Portugues de Oncologia de Francisco Gentil - Centro de Lisboa	Lisbon		Portugal	1093
26	UniversitaetsSpital	Zurich		Switzerland	CH-8091
27	Addenbrooke's NHS Trust	Cambridge	England	United Kingdom	CB2 2QQ
28	St. James's Hospital	Leeds	England	United Kingdom	LS9 7TF
29	Royal Marsden NHS Trust	London	England	United Kingdom	SW3 6JJ
30	Christie Hospital N.H.S. Trust	Manchester	England	United Kingdom	M20 9BX
31	Weston Park Hospital	Manchester	England	United Kingdom	M20 9BX
32	Clatterbridge Centre for Oncology NHS Trust	Merseyside	England	United Kingdom	CH63 4JY
33	Southend NHS Trust Hospital	Westcliff-On-Sea	England	United Kingdom	SS0 0RY