Randomized phase III trial to compare the effectiveness of radiation therapy with or without
thalidomide in treating patients who have brain metastases. Radiation therapy uses
high-energy x-rays to damage tumor cells. Drugs such as thalidomide may stop the growth of
brain metastases by stopping blood flow to the tumor. It is not yet known whether radiation
therapy is more effective with or without thalidomide in treating brain metastases.
I. Compare the overall survival of patients with multiple brain metastases treated with
radiotherapy with or without thalidomide.
II. Compare the time to tumor progression in patients treated with these regimens.
III. Compare the time to neuro-cognitive progression in patients treated with these
IV. Compare the cause of death distribution in patients treated with these regimens.
V. Compare the frequency of toxic effects of these regimens in these patients. VI. Evaluate
and compare the quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
recursive partitioning analysis class (I vs II) and planned chemotherapy after whole brain
irradiation (yes vs no). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients undergo radiotherapy once daily 5 days a week for 3 weeks. Arm II: Patients
undergo radiotherapy as in arm I. Beginning on the first day of radiotherapy, patients
receive oral thalidomide once daily.
Treatment with thalidomide continues for 2 years in the absence of disease progression or
unacceptable toxicity. Quality of life is assessed at baseline, at completion of
radiotherapy, and then every 2 months for 1 year.
Patients are followed every 2 months for 1 year, every 4 months for 1 year, every 6 months
for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 332 patients (166 per treatment arm) will be accrued for this
study within 14.5 months.
- Histologically confirmed extracranial primary malignancy
- Multiple brain metastases
- At least 1 measurable brain metastasis by MRI
- More than 4.0 cm
- Located in midbrain or brainstem (radiosurgery ineligible)
- Performance status - Zubrod 0-1
- At least 8 weeks
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 11 g/dL*
- Hematocrit at least 35%*
- Bilirubin no greater than 1.5 mg/dL
- ALT no greater than 2 times normal
- Creatinine no greater than 1.5 mg/dL
- BUN no greater than 25 mg/dL
- No history of deep venous thrombosis
- No sensory neuropathy grade 2 or greater
- No known AIDS
- No other major medical illness or psychiatric impairments that would preclude study
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier method of contraception during and for at
least 4 weeks after study
- No prior thalidomide
- More than 2 weeks since prior chemotherapy
- Concurrent chemotherapy allowed if more than 6 weeks past study entry (allowed during
first 6 weeks of study if disease progression occurs)
- See Disease Characteristics
- No prior radiotherapy to the head or neck
- No prior radiosurgery
- Prior resection of brain metastases allowed
- No concurrent anticoagulant therapy