Radiosurgery With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. It is not yet known if radiosurgery is more effective with or without whole-brain radiation therapy in treating brain metastases. PURPOSE: Randomized phase III trial to compare the effectiveness of radiosurgery with or without whole-brain radiation therapy in treating patients who have brain metastases.

Detailed Description
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OBJECTIVES: Compare the overall survival of patients with 1 to 3 cerebral metastases treated with radiosurgery with or without whole brain radiotherapy. Compare the time to CNS failure (brain) in patients treated with these regimens. Compare the quality of life, duration of functional independence, and long-term neurocognitive status in patients treated with these regimens. Compare the post-treatment toxic effects of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (60 and over vs under 60), extracranial disease (controlled for more than 3 months vs controlled for 3 months or less), and number of brain metastases (1 vs more than 1). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo radiosurgery. Arm II: Patients undergo radiosurgery. Within 14 days, patients then undergo whole brain radiotherapy 5 days a week for 2.5 weeks. Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years. Patients are followed at weeks 6 and 12, every 3 months for 9 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 480 patients (240 per treatment arm) will be accrued for this study within 5 years.

Official Title
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A Phase III Randomized Trial Of The Role Of Whole Brain Radiation Therapy In Addition To Radiosurgery In The Management Of Patients With One To Three Cerebral Metastases

Conditions
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Metastatic Cancer

Intervention / Treatment
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* Radiation: radiation therapy
* Procedure: surgery
* Radiation: WBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cerebral metastases meeting all of the following requirements: 1-3 de novo lesions Metastases must be from a histologically confirmed extracerebral primary site, another metastatic site, or from the metastatic brain lesion(s) Each lesion must be less than 3.0 cm by contrasted MRI of the brain Lesions must not be within 5 mm of optic chiasm or within the brainstem No primary germ cell tumor, small cell carcinoma, or lymphoma No leptomeningeal metastases Eligible for treatment with gamma knife or linear accelerator-based radiosurgery Performance status - ECOG 0-2 Performance status - Zubrod 0-2 Not pregnant Negative pregnancy test Fertile patients must use effective contraception * Male patients must continue to use contraception for 3 months after the completion of radiotherapy No pacemaker or other MRI-incompatible metal in body No known allergy to gadolinium Deemed to be at low risk for recurrence from any prior malignancies At least 7 days since prior chemotherapy Concurrent hormonal agents allowed Concurrent steroids allowed No prior cranial radiotherapy No prior resection of cerebral metastasis Concurrent anticonvulsants allowed provided therapeutic serum/plasma level maintained before study intervention

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 |
| --- | --- |
| Experimental: radiosurgery<br>Patients undergo radiosurgery. Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years. | Radiation: radiation therapy<br> <br> Procedure: surgery<br> <br> |
| Experimental: radiosurgery + WBRT<br>Patients undergo radiosurgery. Within 14 days, patients then undergo whole brain radiotherapy 5 days a week for 2.5 weeks. Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years. Patients are followed at weeks 6 and 12, every 3 months for 9 months, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter. | Radiation: radiation therapy<br> <br> Procedure: surgery<br> <br> Radiation: WBRT<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to CNS failure |  | Up to 4 years | 
| Change in QOL between SRS and SRS + WBRT treatment groups using the FACT-BR questionnaire |  | From baseline to up to 3 months | 
| Change in the duration of functional independence using the Barthel ADL Index score |  | From baseline to up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tumors metastatic to brain