Stereotactic Radiosurgery or Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases That Have Been Removed By Surgery
Condition: Cognitive/Functional Effects; Metastatic Cancer; Neurotoxicity; Radiation Toxicity; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Neurotoxicity Syndromes
Intervention: stereotactic radiosurgery; whole-brain radiation therapy
Intervention description: Undergo RT; Undergo radiotherapy (RT)
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 194.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: neurotoxicity; radiation toxicity; cognitive/functional effects; tumors metastatic to brain; unspecified adult solid tumor, protocol specific

Summary:

      RATIONALE: Stereotactic radiosurgery may be able to 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 radiosurgery is more effective than
      whole-brain radiation therapy in treating patients with brain metastases that have been
      removed by surgery.

      PURPOSE: This randomized phase III trial studies how well stereotactic radiosurgery works
      compared to whole-brain radiation therapy in treating patients with brain metastases that
      have been removed by surgery.
    

Eligibility criteria:

        Pre-registration Inclusion Criteria:

          1. Number of Brain Metastases - Four or fewer brain metastases (as defined on the
             pre-operative MRI or CT brain scan) and status post resection of one of the lesions.

          2. Non-CNS Primary Site - Pathology from the resected brain metastasis must be consistent
             with a non-central nervous system primary site. Note: Patients with or without active
             disease outside the nervous system are eligible (including patients with unknown
             primaries), as long as the pathology from the brain is consistent with a non-central
             nervous system primary site.

          3. Size of Metastases - Any unresected lesions must measure < 3.0 cm in maximal extent on
             the contrasted MRI or CT brain scan obtained ≤ 35 days prior to pre-registration. The
             unresected lesions will be treated with SRS as outlined in the treatment section of
             the protocol. Note: The metastases size restriction does not apply to the resected
             brain metastasis; with resected brain metastases only surgical cavity size determines
             eligibility.

          4. Size of Resection Cavity - Resection cavity must measure <5.0 cm in maximal extent on
             the post-operative MRI or CT brain scan obtained ≤35 days prior to pre-registration.

             Note: It is permissible for the resection of a dominant brain metastasis to include a
             smaller "satellite" metastasis as long as the single resection cavity is less than the
             maximum size requirements.

          5. Tumor Staging Procedures - All standard tumor-staging procedures necessary to define
             baseline extra cranial disease status completed ≤42 days prior to pre-registration.

          6. Treatment with Gamma Knife or Radiosurgery - Able to be treated with either a gamma
             knife or a linear accelerator-based radiosurgery system.

          7. Age ≥ 18 years

          8. Neurocognitive Testing - Willing and able to complete neurocognitive testing without
             assistance from family and companions. Note: Because neurocognitive testing is one of
             the primary goals of this study, patients must be able to utilize English language
             booklets (and/or French booklets if enrolled in Canada).

          9. Quality of Life (QOL) Questionnaires - Willing and able to complete QOL by themselves
             or with assistance

         10. ECOG Performance Status - ECOG Performance Status (PS) 0, 1, or 2.

         11. SRS Credentialed by IROC Houston Quality Assurance - The site's SRS facility is IROC
             Houston Quality Assurance approved.

         12. Neurocognitive Testing Credentialing - The site study team member performing
             neurocognitive testing of patients must have credentialing confirming completion of
             the neurocognitive testing training of the protocol.

         13. Written Informed Consent - Provide written informed consent

         14. Mandatory Samples for Correlative Tests - Willing to provide mandatory blood and urine
             samples for correlative research purposes.

        Pre-registration Exclusion Criteria:

          1. Pregnancy, Nursing and Contraception - pregnant women, nursing women and men or women
             of childbearing potential who are unwilling to employ adequate contraception
             throughout the study and for men for up to 3 months after completing treatment.

          2. Prior Cranial Radiation Therapy

          3. MRI or CT Scans - Inability to complete a MRI or CT scan with contrast of the head.

          4. Gadolinium Allergy - Known allergy to gadolinium.

          5. Cytotoxic Chemotherapy - Planned cytotoxic chemotherapy during the SRS or WBRT.

          6. Other Tumor Types - Primary germ cell tumor, small cell carcinoma, or lymphoma

          7. Leptomeningeal Metastasis - Widespread definitive leptomeningeal metastasis

          8. Location of Brain Metastasis - A brain metastasis that is located ≤ 5 mm of the optic
             chiasm or within the brainstem.

        Randomization Inclusion Criteria:

          1. Number of Unresected Lesions - Post-operative MRI or CT scan confirmed zero, one, two
             or three unresected lesions.

             1.1 Each unresected lesion must measure ≤ 3.0 cm in maximal extent on the contrasted
             post-operative MRI or CT brain scan.

             1.2 Note: The pre-registration, post-operative, brain scan may be used for the
             randomization scan if obtained ≤ 28 days prior to randomization.

             1.3 Note: If there are no unresected brain metastases (i.e., all brain metastases have
             been resected), a post-operative CT brain scan may be used if obtained ≤ 28 days prior
             to randomization.

          2. Size of Resection Cavity - Post-operative MRI or CT scan confirms resection cavity
             measures < 5.0 cm in maximal extent.

             2.1 Note: The pre-registration, post-operative brain scan may be used for the
             randomization scan if obtained ≤ 28 days prior to randomization.

             2.2 Note: If there are no unresected brain metastases (i.e., all brain metastases have
             been resected), a post-operative CT brain scan may be used if obtained ≤28 days prior
             to randomization.

          3. Urine or Serum Pregnancy Test - Negative urine or serum pregnancy test done ≤ 7 days
             prior to randomization, for women of child bearing potential only.

        Randomization Exclusion Criteria: none