A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases

Study Overview
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Brief Summary
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This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).

Detailed Description
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Recently, a novel treatment strategy for large brain metastases was described whereby lesions appropriate for resection were treated with a single fraction of SRS pre-operatively. In a retrospective analysis, of 51 lesions with a median tumor size of 3 cm, 1-year LC was 86%. This neoadjuvant approach resulted in lower rates of leptomeningeal failure (3 vs. 17%) and symptomatic radiation toxicity (1.5 vs. 14.6 %) compared to a comparative cohort of lesions treated with post-operative cavity boost SRS (POCBS). Based on promising results, we believe that a prospective trial to establish the value of neoadjuvant SRS (NaSRS) for the treatment of BM appropriate for resection is warranted. This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).

Official Title
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A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases

Conditions
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Brain Metastases

Intervention / Treatment
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* Radiation: Stereotactic Radiosurgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Lymphoma, small cell carcinoma, and seminoma are excluded A lesion appropriate for resection, not previously treated with SRS. Lesions should be > 2 cm and < 4 cm in largest dimension, and require resection ( e.g. due to mass effect or to obtain a tissue diagnosis). Index lesions will be treated with SRS and surgery, as outlined in the treatment section of the protocol. Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate NaSRS, e.g., the ability to lie flat in a stereotactic head frame. Any unresected lesions or lesions for which there is no planned immediate resection (non index lesions) must measure < 3.0 cm in maximal extent on the contrasted MRI or CT brain scan obtained ≤ 35 days prior to pre-registration. Unresected lesions will be treated with SRS as outlined in the treatment section of the protocol. . ECOG ≤ 2 MRI confirmed 1-6 lesions, one of which is the index lesion. Each non-index lesion (up to 5) must measure ≤ 3.0 cm in maximal extent on contrasted MRI scan, and not otherwise require resection. Note: The pre-registration MRI may be obtained ≤ 35 days prior to enrolment. Exclusion Criteria: Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved. pregnancy Prior cranial radiotherapy targeting the index lesion, or any prior WBRT. Inability to complete a MRI with contrast of the head, or a known allergy to gadolinium. Cytotoxic Chemotherapy within 7 days prior to SRS (molecularly targeted therapies , including immune-modulatory drugs, can be given within seven days of SRS at the discretion of the treating physician) Metastatic germ cell tumor, small cell carcinoma, or lymphoma or any primary brain tumor Imaging Findings: Widespread definitive leptomeningeal metastasis. A brain metastasis that is located ≤ 2 mm of the optic chiasm Evidence of midline shift Fourth ventricular narrowing, concerning for hydrocephalus

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Patients with resectable brain mets will receive neoadjuvant stereotactic radiosurgery prior to surgical resection.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm 1<br>Neoadjuvant SRS | Radiation: Stereotactic Radiosurgery<br>* Stereotactic Radiosurgery before surgical resection of brain mets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation toxicity | The rate at 1 year of symptomatic (≥grade 2) radiation toxicity | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local control | 1-year local control (PR+CR) of the index lesion resulting from NaSRS | 1 year | 
| leptomeningeal disease | 1-year rates of leptomeningeal disease | 1 year | 
| Survival | Median survival | 5 years | 
| progression-free survival |  | 2 years | 
| overall survival |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stereotactic Radiosurgery, Radiation, Surgery