Phase III Trial of Post-Surgical Single Fraction Stereotactic Radiosurgery (SRS) Compared With Fractionated SRS for Resected Metastatic Brain Disease
Overview
- Phase
- Phase 3
- Intervention
- Quality-of-Life Assessment
- Conditions
- Metastatic Malignant Neoplasm in the Brain
- Sponsor
- Alliance for Clinical Trials in Oncology
- Enrollment
- 242
- Locations
- 232
- Primary Endpoint
- Surgical bed recurrence-free survival (SB-RFS)
- Status
- Active, not recruiting
- Last Updated
- 11 days ago
Overview
Brief Summary
This phase III trial studies how well single fraction stereotactic radiosurgery works compared with fractionated stereotactic radiosurgery in treating patients with cancer that has spread to the brain from other parts of the body and has been removed by surgery. Single fraction stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Fractionated stereotactic radiosurgery delivers multiple, smaller doses of radiation therapy over time. This study may help doctors find out if fractionated stereotactic radiosurgery is better or worse than the usual approach with single fraction stereotactic radiosurgery.
Detailed Description
PRIMARY OBJECTIVES: I. To ascertain if time to surgical bed failure is increased with fractionated stereotactic radiosurgery (FSRS) compared to single-fraction stereotactic radiosurgery (SSRS) in patients with resected brain metastasis. SECONDARY OBJECTIVES: I. To ascertain if there is better emotional well-being at 9 months as assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-BR) in patients with resected brain metastasis undergoing FSRS compared to SSRS (Primary quality of life \[QOL\] objective). II. To ascertain whether there is improved overall survival in patients with resected brain metastases who undergo FSRS compared to patients who receive SSRS. III. To ascertain in patients with resected brain metastases whether there is improved overall QOL as assessed by the FACT-BR and Linear Analog Self-Assessment (LASA) in patients who receive FSRS compared to patients who receive SSRS (Secondary QOL objective). IV. To compare the functional independence in patients who receive FSRS to patients who receive SSRS. V. To tabulate and descriptively compare the post-treatment adverse events associated with the interventions, including the potential impact of immunotherapy and targeted therapy. VI. To compare rates of radiation necrosis at 12 months in patients who receive FSRS to patients who receive SSRS. VII. To evaluate if there is any difference in central nervous system (CNS) failure patterns (local, distant brain failure, local leptomeningeal disease, widespread leptomeningeal disease) in patients who receive FSRS compared to patients who receive SSRS after resection of brain metastasis. VIII. To ascertain in patients with resected brain metastases whether there is increased time to whole-brain radiotherapy (WBRT) in patients who receive FSRS compared to patients who receive SSRS. IX. To determine in long-term survivors (patients who are alive more than 12 months from time of randomization) whether there is better emotional well-being and overall QOL as assessed by the FACT-BR and LASA in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Secondary QOL objective). X. To assess for differences in CNS failure patterns (surgical, local, distant brain failure, leptomeningeal disease) as well as radiation necrosis rates as assessed by central review in patients who receive FSRS compared to patients who receive SSRS after resection of a brain metastasis. XI. To ascertain in patients with resected brain metastases whether there is improved QOL as assessed by all other total and individual FACT-BR and LASA items and subscale values in patients who receive FSRS compared to patients who receive SSRS (Exploratory QOL objective). XII. To determine in patients with resected brain metastases whether there is less cognitive progression in patients who receive FSRS to the surgical bed compared to patients who receive SSRS (Exploratory cognitive objective). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo SSRS over 1 session. ARM II: Patients undergo FSRS over 3 or 5 daily sessions. After completion of study, patients are followed up at 30 days, at 3, 6, 9, 12, 16, and 24 months, then every 6 months until 5 years from randomization.
Investigators
Eligibility Criteria
Inclusion Criteria
- •PRE-REGISTRATION:
- •Pathology from the resected brain metastasis must be consistent with a non-central nervous system primary site. 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.
- •Three or fewer (i.e. 0 to 3) unresected brain metastases (as defined on the post operative magnetic resonance imaging \[MRI\]) at the time of screening.
- •o Note: Dural based metastases (e.g. commonly seen in breast cancer) are eligible.
- •Unresected lesions must measure \< 4.0 cm in maximal extent on the contrasted post-operative treatment MRI brain scan. The unresected lesions will be treated with SRS as outlined in the treatment section of the concept.
- •o Note: The metastases size restriction does not apply to the resected brain metastasis.
- •One brain metastasis must be completely (gross total resection) resected =\< 30 days prior to pre-registration.
- •o NOTE: May not have had resection of more than one brain metastasis.
- •The resected brain metastasis must measure 2 cm or larger on the pre-operative MRI.
- •Resection cavity must measure \< 5.0 cm in maximal extent and the resection must be complete (gross total resection) on the post-operative MRI obtained =\< 30 days prior to pre-registration.
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (SSRS)
Patients undergo SSRS over 1 session.
Intervention: Quality-of-Life Assessment
Arm I (SSRS)
Patients undergo SSRS over 1 session.
Intervention: Questionnaire Administration
Arm II (FSRS)
Patients undergo FSRS over 3 or 5 daily sessions.
Intervention: Fractionated Stereotactic Radiosurgery
Arm II (FSRS)
Patients undergo FSRS over 3 or 5 daily sessions.
Intervention: Quality-of-Life Assessment
Arm II (FSRS)
Patients undergo FSRS over 3 or 5 daily sessions.
Intervention: Questionnaire Administration
Arm I (SSRS)
Patients undergo SSRS over 1 session.
Intervention: Single Fraction Stereotactic Radiosurgery
Outcomes
Primary Outcomes
Surgical bed recurrence-free survival (SB-RFS)
Time Frame: From the time of randomization up to 2 years post radiation
Surgical bed control is defined as the absence of new nodular contrast enhancement in the surgical bed. In other words, a surgical bed recurrence-free survival (SB-RFS) event is defined as radiographic evidence of a new contrast-enhancing lesion (specifically any new progressive enhancing nodularity) at the site of the surgical resection. Will use a stratified log-rank test that compares and will report the median SB-RFS times between the single fraction stereotactic radiosurgery (SSRS) and fractionated stereotactic radiosurgery (FSRS) arms while adjusting for the stratification factors.
Secondary Outcomes
- Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score for long-term survivors(At 12 months)
- Karnofsky Performance Status (KPS)(Up to 24 months)
- Time until whole-brain radiotherapy (WBRT) due to any reason (e.g. surgical bed recurrence, recurrence/progression at another central nervous system [CNS] site)(Up to 24 months)
- Change in Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale score(At 9 months)
- Functional Assessment of Cancer Therapy-Brain (FACT-BR) Emotional sub-scale score for long-term survivors(At 12 months)
- Barthel Activities of Daily Living (ADL) Index(Up to 24 months)
- Functional Assessment of Cancer Therapy-Brain (FACT-BR) total score(At 9 months)
- Linear Analog Self-Assessment (LASA) overall quality of life(At 9 months)
- Incidence of adverse events(Up to 24 months)
- Linear Analog Self-Assessment (LASA) overall quality of life for long-term survivors(At 12 months)
- Karnofsky Performance Status (KPS) for long-term survivors(Up to 24 months)
- Barthel Activities of Daily Living (ADL) Index for long-term survivors(Up to 24 months)
- Overall survival(Up to 5 years)
- Proportion of patients with radiation necrosis(At 24 months)