Pre-Operative vs. Post-Operative Stereotactic Radiosurgery for Operative Metastatic Brain Tumors
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Malignant Solid Neoplasm
- Sponsor
- Mayo Clinic
- Enrollment
- 140
- Locations
- 4
- Primary Endpoint
- Central nervous system (CNS) composite endpoint event (CNS-CE event)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This phase III trial studies the side effects and how well stereotactic radiosurgery (SRS) works before or after surgery in patients with tumors that has spread to the brain or that can be removed by surgery. 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.
Detailed Description
PRIMARY OBJECTIVE: I. To determine for patients with brain metastases meeting the inclusion criteria, whether there is an increase in the time to a composite endpoint of adverse outcomes including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis in patients who receive SRS prior to surgery as compared to patients who receive surgery prior to SRS. SECONDARY OBJECTIVES: I. To determine for patients with brain metastases whether there is improved overall survival for patients who receive SRS prior to surgery as compared to patients who receive SRS after surgery. II. To determine for patients with brain metastases whether there are improved patient reported outcomes including quality of life for patients who receive SRS prior to surgery as compared to patients who receive SRS after surgery. III. To determine if preoperative SRS increases rates of surgical morbidity including postoperative complications such as wound infection, need for longer hospital stays, or readmission compared to a surgery first approach for resectable brain metastases. IV. To determine for patients with brain metastases whether there is a higher rate of completion of planned therapies for patients who receive SRS prior to surgery as compared to patients who receive surgery prior to SRS. V. To determine for patients with brain metastases whether there is a shorter time to initiation or re-initiation of systemic therapy with pre-operative versus post-operative SRS. VI. To determine for patients treated with pre-operative SRS whether there is a longer interval to regional progression, any central nervous system (CNS) progression or need for subsequent intracranial treatment compared to patients receiving post-operative SRS. VII. To determine for patients with pre-operative as compared to post-operative radiation whether there is a decreased rate of radiation necrosis, including asymptomatic and symptomatic radiation necrosis. VIII. To determine for patients with pre-operative as compared to post-operative radiation whether there is a decreased rate of local recurrence. IX. To determine for patients with pre-operative as compared to post-operative radiation whether there is a decreased rate of leptomeningeal disease. CORRELATIVE RESEARCH OBJECTIVES: I. To determine the genetic and molecular alterations of brain metastases seen after radiation versus in the setting of resection alone, including early radiobiologic changes in tissue treated with SRS 24 to 48 hours prior, and to investigate detection rate of corresponding circulating deoxyribonucleic acid (DNA) and/or inflammatory markers in peripheral specimens. II. To investigate the usefulness of biomarkers and response to radiation in predicting local control and outcomes. III. To look at cell capture of tumor cells as well as cell free DNA in cerebrospinal fluid (CSF) sampled at the time of surgery, comparing patients receiving neoadjuvant treatment to those that have not. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients undergo surgery on day 1. Within 2 weeks, patients undergo stereotactic radiosurgery. ARM B: Patients undergo stereotactic radiosurgery on day 1. Within 4 weeks, patients undergo surgery. Patients also undergo a planning computed tomography (CT) or magnetic resonance imaging (MRI) before radiation and tissue and CSF sample collection at time of surgery. Additionally, patients undergo MRI and option blood sample collection throughout the study. After completion of study treatment, patients are followed up at 2 weeks, every 3-4 months for up to 2 years and then periodically for up to 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \>= 18 years
- •Histological or cytological confirmation of solid tumor malignancy and/or clinical history of known or suspected metastatic disease with an intraparenchymal brain tumor consistent with brain metastasis based on clinical and radiologic findings
- •Clinical indication for surgical resection of one brain metastasis based on neurosurgery recommendation and patient deemed a surgical candidate
- •Clinical indication and plan for stereotactic radiosurgery to all known brain lesions requiring treatment (=\< 10 metastases)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2
- •Provide written informed consent or have a legally authorized representative who is responsible for the care and well-being of the potential study participant, provide consent
- •Willing to continue follow-up visits, either at the enrolling institution or with a local medical doctor as clinically appropriate, and according to the study timeline. Clinical notes and digital copies of imaging must be provided to the enrolling site if follow-up is done externally
Exclusion Criteria
- •Any of the following:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy. \* NOTE: Patients known to be HIV, but without clinical evidence of an immunocompromised state, are eligible for this trial
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Prior open neurosurgery for malignancy
- •Known or clinically suspected primary germ cell tumor, small cell carcinoma, or lymphoma
- •History of whole brain radiation therapy (WBRT)
Outcomes
Primary Outcomes
Central nervous system (CNS) composite endpoint event (CNS-CE event)
Time Frame: Time from study randomization to documentation of the first CNS-CE event, assessed up to 5 years
The CNS-CE event distributions will be estimated using the Kaplan-Meier method.
Secondary Outcomes
- Overall survival (OS)(Up to 5 years)
- Incidence of adverse events(Up to 5 years post treatment)
- CNS-CE event free survival time adjusted for stratification factors(Up to 5 years)
- Time to regional progression(Up to 5 years post treatment)
- Time central nervous system (CNS) progression(Up to 5 years post treatment)
- CNS-CE event free rate(At 6 months)
- Patient-reported outcome - Quality of Life (QOL)(Baseline to 6 months post treatment)
- Rate of completion of therapies(Up to 5 years post treatment)
- Time to systemic therapy(Time to initiation or re-initiation of systemic therapy with pre-operative versus post-operative SRS, assessed up to 5 years)
- Time to subsequent treatment, including whole-brain radiotherapy (WBRT)(Up to 5 years)
- Rate of neurosurgical morbidity(Up to 5 years post treatment)