A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03368625
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University Health Network, Toronto
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	David Shultz, MD
Principal Investigator Affiliation	University Health Network, Toronto
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Canada, Germany
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Brain Metastases

Additional Details

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.#46; 17%) and symptomatic radiation toxicity (1.5 vs.#46; 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).

Arms & Interventions

Arms

Other: Arm 1

Neoadjuvant SRS

Interventions

Radiation: - Stereotactic Radiosurgery

Stereotactic Radiosurgery before surgical resection of brain mets.

Contact a Trial Team

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