RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as temozolomide may make the tumor cells more sensitive to radiation therapy. Combining temozolomide with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving temozolomide together with whole-brain radiation therapy works in treating patients with brain metastasis secondary to non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
brain metastases Non-small cell lung cancer	Drug: temozolomide  Procedure: chemotherapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the intracranial response rate in patients with brain metastasis secondary to non-small cell lung cancer treated with whole brain radiotherapy and temozolomide.

Secondary

• Determine the time to radiological progression in patients treated with this regimen.
• Determine the time to neurological progression (confirmed by MRI) in patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients undergo whole brain radiotherapy once daily, 5 days a week, for 2 weeks (10 fractions). Patients also receive concurrent oral temozolomide once daily on days 1-14.

Beginning 3 weeks after the completion of chemoradiotherapy, patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of CNS progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer (NSCLC), including the following histologies:
• Squamous cell carcinoma
• Adenocarcinoma
• Large cell carcinoma
• Bronchoalveolar carcinoma
• All variants of NSCLC
• At least 1 bidimensionally measurable brain metastasis
• Confirmed by MRI within the past two weeks
• CT scan is not acceptable
• Biopsy is not required
• Not eligible for surgical resection or radiosurgery of brain metastasis
• Systemic disease not in immediate need of chemotherapy

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 12 weeks

Hematopoietic

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

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST and ALT ≤ 2 times upper limit of normal (5 times ULN if liver metastases are present)
• Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver metastases are present)

Renal

• Creatinine ≤ 1.6 mg/dL

Other

• HIV negative
• No AIDS-related illness
• No poor medical risks due to active nonmalignant systemic disease
• No frequent vomiting
• No medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Prior biologic therapy allowed
• No concurrent growth factors to induce elevations in blood counts for the purposes of administration of study drug at scheduled dosing interval or to allow treatment with study drug at a higher dose

Chemotherapy

• More than 4 weeks since prior chemotherapy
• No prior temozolomide
• No other concurrent chemotherapy during study radiotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiotherapy for local control or palliative therapy for painful bony lesions allowed
• At least 4 weeks since prior radiotherapy to ≥ 15% of bone marrow (2 weeks for < 15% of bone marrow) and recovered
• No prior radiotherapy to ≥ 50% of bone marrow
• No prior radiotherapy to the brain, including stereotactic radiosurgery to a different lesion
• No concurrent intensity modulated radiotherapy or 3-D cranial radiotherapy
• Concurrent radiotherapy to painful bony lesions allowed provided no more than 15% of bone marrow is irradiated

Surgery

• Prior surgery for brain metastasis allowed

Other

• No other concurrent investigational agents
• No other concurrent treatment for brain metastasis

Study chairs or principal investigators

Minesh P. Mehta, MD,  University of Wisconsin Comprehensive Cancer Center   
H. Ian Robins, MD, PhD,  Study Chair,  University of Wisconsin Comprehensive Cancer Center   

Study ID Numbers:  CDR0000357567; ECOG-E1F03; NCT00080938
Record last reviewed:  January 2005
Last Updated:  April 5, 2005
Record first received:  April 7, 2004
ClinicalTrials.gov Identifier:  NCT00080938
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08