RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of radiation therapy plus temozolomide to that of radiation therapy alone in treating patients who have non-small cell lung cancer that is metastatic to the brain.

Condition	Treatment or Intervention	Phase
brain metastases	Procedure: chemotherapy  Procedure: radiation therapy  Drug: temozolomide	Phase II

Further Study Details: 

OBJECTIVES: I. Compare the time to symptomatic neurologic progression, in terms of worsening in 1 or more of 6 clinical categories including headaches, focal weakness, mentation and/or communication, visual changes, coordination, and new cranial neuropathy, in patients with brain metastases from non-small cell lung cancer treated with whole brain radiotherapy with or without temozolomide. II. Compare the time to progression in patients treated with these regimens. III. Compare the overall response rate and overall survival in patients treated with these regimens. IV. Compare changes in disease-related symptoms in patients treated with these regimens. V. Compare the effect of these regimens on steroid usage and seizure frequency in these patients.

PROTOCOL OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to prior chemotherapy (yes vs no) and recursive partitioning analysis classification (1 vs 2). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral temozolomide once daily on days 1-7 and 15-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive whole brain radiotherapy once daily 5 days a week for 2 weeks beginning on day 1. Arm II: Patients receive oral placebo and radiotherapy as in arm I. Quality of life is assessed on day 1 of each course, on day 30 after the last course, and then every 8 weeks until disease progression. Patients are followed at 30 days and then every 8 weeks thereafter.

PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically confirmed non-small cell lung cancer

• Squamous cell carcinoma
• Adenocarcinoma (including large cell carcinoma)
• Non-small cell cancer not otherwise specified

Brain metastases

• Biopsy not required
• Ineligible for surgical resection or radiosurgery

Systemic disease that is not in immediate need of chemotherapy

--Prior/Concurrent Therapy--

Biologic therapy: No concurrent immunotherapy or biologic therapy except growth factors

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy and recovered
• No more than 1 prior chemotherapy regimen for systemic metastatic disease
• No prior chemotherapy for brain metastases
• No prior temozolomide
• Concurrent chemotherapy (docetaxel, paclitaxel, or cisplatin) to alleviate progressing systemic disease is allowed

Endocrine therapy: Concurrent dexamethasone required

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy to 15% or more of total bone marrow (2 weeks for less than 15% of bone marrow) and recovered
• No prior radiotherapy to 50% or more of total bone marrow
• No prior radiotherapy to the brain
• Prior radiotherapy for local control or palliative therapy for a painful bony lesion allowed
• Concurrent radiotherapy to painful bony lesions allowed if no more than 15% of bone marrow is irradiated

Surgery:

• See Disease Characteristics
• Prior surgery for brain metastases allowed

Other:

• No other concurrent investigational drugs
• Recovered from toxic effects of all prior therapies

--Patient Characteristics--

Age: 18 and over

Performance status: Karnofsky 70-100%

Life expectancy: More than 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 2 times ULN (5 times ULN if liver metastases present)
• Alkaline phosphatase no greater than 2 times ULN (5 times ULN if liver metastases present)

Renal:

• BUN no greater than 1.5 times ULN
• Creatinine no greater than 1.5 times ULN

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known HIV positivity or AIDS-related illness
• No active nonmalignant systemic disease
• No frequent vomiting or other medical condition that would preclude oral medication intake (e.g., partial bowel obstruction)
• No other prior or concurrent malignancies within the past 5 years except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States

Study chairs or principal investigators

Lauren E. Abrey,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000069201; MSKCC-01133; NCI-G01-2048; SPRI-P02143
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  February 14, 2002
ClinicalTrials.gov Identifier:  NCT00030836
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08