Radiation Therapy With or Without Thalidomide in Treating Patients With Brain Metastases

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: 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 regimens. 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.

Official Title
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A Phase III Study of Conventional Radiation Therapy Plus Thalidomide (NSC#66847) Versus Conventional Radiation Therapy for Multiple Brain Metastases

Conditions
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Tumors Metastatic to Brain

Intervention / Treatment
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* Radiation: radiation therapy
* Drug: thalidomide
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 therapy 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (radiation therapy)<br>Patients undergo radiotherapy once daily 5 days a week for 3 weeks. | Radiation: radiation therapy<br>* Undergo conventional radiation therapy<br>* Other names: therapy, radiation;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|
| Experimental: Arm II (radiation therapy, thalidomide)<br>Patients undergo radiotherapy as in arm I. Beginning on the first day of radiotherapy, patients receive oral thalidomide once daily. | Radiation: radiation therapy<br>* Undergo conventional radiation therapy<br>* Other names: therapy, radiation;Drug: thalidomide<br>* Given orally<br>* Other names: Thalomid;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The log-rank statistic will be used. | Up to 6 years | 
| Time to tumor progression | Cumulative incidence model will be used to analyze the data. A multivariate Cox model analysis will be performed. | Date of randomization to documentation of progression, assessed up to 6 years | 
| Time to neuro-cognitive progression as assessed by the Mini Mental State Exam | Cumulative incidence model will be used to analyze the data. | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cause of death distribution |  | Up to 6 years | 
| Frequency of toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 |  | Up to 6 years | 
| Quality of life as measured by the Spitzer Quality of Life Index (SQLI) |  | 6 months | 
| Quality of life as measured by the SQLI |  | 12 months |