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

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ClinicalTrials.gov Identifier: NCT00377156
Recruitment Status : Completed
First Posted : September 15, 2006
Results First Posted : August 24, 2017
Last Update Posted : September 16, 2022
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Brief Summary:

RATIONALE: Stereotactic radiation therapy can send x-rays directly to the tumor and cause less damage to normal tissue. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether stereotactic radiation therapy is more effective with or without whole-brain radiation therapy in treating patients with brain metastases.

PURPOSE: This randomized phase III trial is studying stereotactic radiation therapy and whole-brain radiation therapy to see how well they work compared with stereotactic radiation therapy alone in treating patients with brain metastases.

Condition or disease Intervention/treatment Phase
Breast Cancer Cognitive/Functional Effects Lung Cancer Metastatic Cancer Prostate Cancer Radiation: radiation therapy Radiation: stereotactic radiosurgery Phase 3

Detailed Description:



  • Compare the overall survival of patients with 1 to 3 cerebral metastases treated with stereotactic radiosurgery with vs without whole-brain radiotherapy.


  • Compare time to CNS (brain) failure in patients treated with these regimens.
  • Compare quality of life, duration of functional independence, and long-term neurocognitive status of patients treated with these regimens.
  • Compare post-treatment toxicity in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (18 to 59 vs 60 and over), extracranial disease (controlled for ≤ 3 months vs controlled for > 3 months), and number of brain metastases (1 vs 2 vs 3). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo stereotactic radiosurgery (SRS).
  • Arm II: Patients undergo SRS as in arm I. Within 14 days, patients then undergo whole-brain radiotherapy 5 days a week for 2.5 weeks.

Quality of life, functional independence, and neurocognitive status are assessed at baseline, at the beginning of each treatment, at weeks 6 and 12, and then at 6, 9, 12, 16, 24 , 36, 48, and 60 months.

PROJECTED ACCRUAL: A total of 238 patients will be accrued for this protocol.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 213 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III Randomized Trial of the Role of Whole Brain Radiation Therapy in Addition to Radiosurgery in Patients With One to Three Cerebral Metastases
Actual Study Start Date : July 2006
Actual Primary Completion Date : October 2014
Actual Study Completion Date : December 15, 2019

Arm Intervention/treatment
Active Comparator: Arm I
Patients undergo stereotactic radiosurgery (SRS)
Radiation: stereotactic radiosurgery
Experimental: Arm II
Patients undergo SRS as in arm I. Within 14 days, patients then undergo whole-brain radiotherapy 5 days a week for 2.5 weeks.
Radiation: radiation therapy
Patients undergo radiation therapy 5 days a week for 2.5 weeks

Radiation: stereotactic radiosurgery

Primary Outcome Measures :
  1. Neurocognitive Progression as Measured by the Number of Participants With Cognitive Deterioration by 3 Months [ Time Frame: 3 months post radiosurgery ]
    The primary endpoint was cognitive deterioration (progression), defined as a decline of greater than 1 SD from baseline on at least 1 of 7 cognitive tests (all tests are standardized based on published norms and transformed so that higher values represent improved cognition) at the 3-month post-SRS evaluation. The number of participants who experienced cognitive deterioration by 3 months is reported for each arm below. For primary analysis of the 3-month cognitive deterioration endpoint, the Fisher exact 2-group binomial test was used to compare the proportion of evaluable patients with 3-month cognitive deterioration between the 2 groups.

Secondary Outcome Measures :
  1. Number of Participants With Local and Distant Tumor Control up to 3 Months [ Time Frame: Up to 3 months ]
    Number of Participants with Local and Distant Tumor Control up to 3 months is defined as....

  2. Overall Quality of Life, as Measured by Mean Change From Baseline [3 Month] [ Time Frame: From Baseline to 3-Month Evaluation ]
    Quality of Life was assessed using the Functional Assessment of Cancer Therapy-Brain, for which the range is from 0 to 200 and higher scores indicate better QOL. The Quality of Life (QOL) scores were transformed to a 0- to 100-point scale (with 100 being most favorable), in which a 10-point change was considered clinically significant. Intergroup changes in QOL scores were compared using a 2-sample t test.

  3. Long-Term Neurocognitive Status (Long-Term Cognitive Status), as Measured by Percentage of Long-term Survivors With Cognitive Deterioration at 12 Months [ Time Frame: From baseline to 12 months ]
    Long-Term Neurocognitive Status > To ascertain in patients with one to three brain metastases whether there is better long-term neurocognitive status in patients who receive SRS alone (Arm A) compared to patients who receive SRS combined with WBRT (Arm B). Long-term survival status is defined as evaluable patients who survived for at least 12 months and had at least one cognitive assessment on or after 365 days.

  4. Overall Survival [ Time Frame: Up to 5 years ]
    Overall survival, defined as the time from randomization until death due to any cause, was compared between the groups using stratified log-rank tests.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of cerebral metastases meeting the following criteria:

    • One to three presumed brain metastases
    • Metastases must be from a histologically confirmed extracerebral site (e.g., lung, breast, prostate)

      • Histologic confirmation may have been from the primary tumor site, from another metastatic site (e.g., osseous metastasis, adrenal metastasis), or from the metastatic brain lesion(s)
    • Each lesion must measure less than 3.0 cm by contrast MRI of the brain performed within the past 21 days
    • Lesions must not be within 5 mm of the optic chiasm or within the brainstem
  • Eligibility for treatment with gamma knife or linear accelerator-based radiosurgery confirmed by a radiation oncologist
  • No primary germ cell tumor, small cell carcinoma, or lymphoma
  • No leptomeningeal metastases
  • Hormone receptor status not specified


  • Male or female
  • Menopausal status not specified
  • ECOG performance status 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 the body
  • No known allergy to gadolinium


  • More than 7 days since prior and no concurrent chemotherapy
  • No prior cranial radiotherapy
  • No prior resection of cerebral metastases
  • Concurrent hormonal agents, steroids, and/or anticonvulsants allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00377156

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Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
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Study Chair: Paul D. Brown, MD Mayo Clinic
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00377156    
Other Study ID Numbers: N0574
CDR0000499633 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2009-00653 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
First Posted: September 15, 2006    Key Record Dates
Results First Posted: August 24, 2017
Last Update Posted: September 16, 2022
Last Verified: September 2022
Keywords provided by Alliance for Clinical Trials in Oncology:
cognitive/functional effects
tumors metastatic to brain
stage IV breast cancer
stage IV prostate cancer
stage IV non-small cell lung cancer
male breast cancer
recurrent breast cancer
recurrent prostate cancer
recurrent non-small cell lung cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Prostatic Diseases