Temozolomide and Radiation Therapy in Treating Patients With Stage IV Malignant Melanoma With Measurable and Unresectable Cancer of the Central Nervous System

Alliance for Clinical Trials in Oncology

Status and phase: Terminated; Phase 2

Conditions: Metastatic Cancer; Melanoma (Skin)

Treatments: Drug: temozolomide; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00068666

CDR0000327811 (Registry Identifier)

N0274

NCI-2012-02554 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as temozolomide, 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. Combining temozolomide with radiation therapy may make the tumor cells more sensitive to radiation therapy and kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving temozolomide together with radiation therapy works in treating patients with stage IV malignant melanoma with measurable and unresectable cancer limited to the central nervous system.

Full description

OBJECTIVES:

Primary

• Determine the response rate in patients with stage IV malignant melanoma with measurable and unresectable disease of the central nervous system treated with temozolomide and radiotherapy.

Secondary

• Determine the safety of this regimen in these patients.
• Determine the survival of patients treated with this regimen.
• Determine the effect of this regimen on performance status and mental status of these patients.
• Determine the response of extra-cranial disease in patients treated with this regimen.

OUTLINE: Patients receive concurrent chemoradiotherapy comprising whole brain radiotherapy daily on days 1-5, 8-13, and 16-21 and oral temozolomide daily on days 1-5. Subsequent treatment with temozolomide repeats every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 18-41 patients will be accrued for this study within 13-30 months.

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV malignant melanoma with measurable and unresectable disease limited to the central nervous system (CNS)

  • Study entry within 14 days of diagnosis of brain metastases

• Recursive partitioning analysis class I or II

• Disease for which no known standard therapy exists that is potentially curative or proven capable of extending life expectancy

• No meningeal carcinomatosis based on imaging studies or on positive results from CSF analysis

• No evidence of metastatic disease outside of the CNS

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic

• AST no greater than 3 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent uncontrolled infection
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer treated with local resection only
• No prior allergy or intolerance to dacarbazine
• No hypersensitivity to temozolomide or any of its components

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior immunotherapy

Chemotherapy

• No prior temozolomide
• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered

Endocrine therapy

• Concurrent steroids allowed if dose stable for at least 7 days prior to CNS imaging

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 15% of the bone marrow
• No prior radiotherapy to the head and neck area
• No prior radiosurgery

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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41 participants in 1 patient group

radiation + temozolomide

Experimental group

Description:

Patients receive concurrent chemoradiotherapy comprising whole brain radiotherapy daily on days 1-5, 8-13, and 16-21 and oral temozolomide daily on days 1-5. Subsequent treatment with temozolomide repeats every 4 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months.

Treatment:

Radiation: radiation therapy

Drug: temozolomide