Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been terminated.
(low accrual)
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC Identifier:
First received: July 11, 2001
Last updated: September 20, 2012
Last verified: September 2012

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 Intervention Phase
Melanoma (Skin)
Metastatic Cancer
Drug: temozolomide
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Temozolomide Versus Temozolomide + Whole Brain Radiation In Stage IV Melanoma Patients With Asymptomatic Brain Metastases

Resource links provided by NLM:

Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Enrollment: 23
Study Start Date: April 2001
Primary Completion Date: May 2003 (Final data collection date for primary outcome measure)
Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified


  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10 g/dL


  • 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


  • Urea less than 1.5 times ULN
  • Creatinine less than 1.5 times ULN


  • 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


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


  • 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


  • See Disease Characteristics
  • No other concurrent radiotherapy


  • See Disease Characteristics
  • Recovered from the effects of any prior major surgery


  • No other concurrent investigational drugs
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00020839

  Show 33 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Study Chair: Juergen C. Becker, MD, PhD Universitaets-Hautklinik Wuerzburg
  More Information

No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC Identifier: NCT00020839     History of Changes
Other Study ID Numbers: EORTC-18981, EORTC-18981
Study First Received: July 11, 2001
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage IV melanoma
recurrent melanoma
tumors metastatic to brain

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplastic Processes
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Pathologic Processes
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses processed this record on November 27, 2014