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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Metastatic Cancer

Treatments: Radiation: radiation therapy; Procedure: surgery; Radiation: WBRT

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00030628

ACOSOG-Z0300

CDR0000069183 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 480 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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480 participants in 2 patient groups

radiosurgery

Experimental group

Description:

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.

Treatment:

Radiation: radiation therapy

Procedure: surgery

radiosurgery + WBRT

Experimental group

Description:

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.

Treatment:

Radiation: radiation therapy

Procedure: surgery

Radiation: WBRT