Stereotactic Radiosurgery or Whole-Brain Radiation Therapy in Treating Patients with Brain Metastases That Have Been Removed by Surgery
Basic Trial Information
|Phase III||Biomarker/Laboratory analysis, Treatment||18 and over||N107C|
NCI-2011-02676, CDR0000701474, NCCTG-N107C, NCT01372774
TRIAL STATUS: Active
This randomized phase III trial studies stereotactic radiosurgery to see how well it works compared to whole-brain radiation therapy in treating patients with cancer that has spread to the brain from the original tumor and that has been removed by surgery. 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.
Further Study Information
I. To determine in patients with one to four brain metastases whether there is improved overall survival in patients who receive stereotactic radiosurgery (SRS) to the surgical bed compared to patients who receive whole-brain radiotherapy (WBRT).
II. To determine in patients with one to four brain metastases whether there is less neurocognitive progression post-randomization in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
I. To determine in patients with resected brain metastases whether there is improved quality-of-life (QOL) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
II. To determine in patients with one to four brain metastases whether there is equal or longer time to central nervous system (CNS) failure (brain) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
III. To determine in patients with one to four brain metastases whether there is longer duration of functional independence in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
IV. To determine in patients with one to four brain metastases whether there is better long-term neurocognitive status in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
V. To tabulate and descriptively compare the post-treatment adverse events associated with the interventions.
VI. To evaluate local tumor bed recurrence at 6 months with post-surgical SRS to the surgical bed in comparison to WBRT.
VII. To evaluate time to local recurrence with post-surgical SRS to the surgical bed in comparison to WBRT.
VIII. To evaluate if there is any difference in CNS failure patterns (local, distant, leptomeningeal) in patients who receive SRS to the surgical bed compared to patients who receive WBRT.
I. To evaluate radiation changes in the limbic system that may correlate with neurotoxicity using brain magnetic resonance imaging (MRI) or computed tomography (CT) scans.
II. To determine if apolipoprotein (Apo) E (i.e., Apo E2, Apo E3, and Apo E4) genotyping may prove to be a predictor of radiation-induced neurocognitive decline (or neuroprotection).
III. To determine if inflammatory markers (i.e., interleukin [IL]-1, IL-6, and tumor necrosis factor [TNF]-alpha) may prove to be predictors of radiation-induced neurocognitive decline.
XII. To determine if oxidative stress biomarkers (i.e., protein carbonyl content, lipid hydroperoxides, and isoprostane levels) may prove to be predictors of radiation-induced neurocognitive decline.
XIII. To determine if hormone and growth factors (i.e., glucocorticoids [e.g., cortisol], gonadal steroids [e.g., estradiol, testosterone, progesterone], growth hormone, human chorionic gonadotropin [hCG], insulin-like growth factor-1 [IGF-1], and neuronal growth factor [NGF]) may prove to be a predictor of radiation-induced neurocognitive decline.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo WBRT once daily (QD), 5 days a week, for approximately 3 weeks.
ARM II: Patients undergo SRS using a gamma knife or a linear accelerator procedure.
After completion of study therapy, patients are followed up at 12 weeks and then 6, 9, 12, 16, and 24 months.
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
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
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; Note: the metastases size restriction does not apply to the resected brain metastasis; with resected brain metastases only surgical cavity size determines eligibility
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
All standard tumor-staging procedures necessary to define baseline extracranial disease status completed =< 42 days prior to pre-registration
Able to be treated with either a gamma knife or a linear accelerator-based radiosurgery system
Willing and able to complete neurocognitive examination 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)
Willing and able to complete quality-of-life (QOL) questionnaires by themselves or with assistance
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
Provide written informed consent
Willing to provide mandatory blood and urine samples for correlative research purposes
Negative urine or serum pregnancy test done =< 7 days prior to randomization, for women of child bearing potential only
Any of the following:
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
Prior cranial radiotherapy
Inability to complete a MRI or CT scan with contrast of the head
Known allergy to gadolinium
Planned cytotoxic chemotherapy during the SRS or WBRT
Primary germ cell tumor, small cell carcinoma, or lymphoma
Widespread definitive leptomeningeal metastasis
Brain metastasis that is located =< 5 mm of the optic chiasm or within the brainstem
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
Alliance for Clinical Trials in Oncology
- National Cancer Institute
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01372774
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.