Preoperative Stereotactic Radiosurgery for Brain Metastases

Overseen By Michael Yu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Cytotoxic chemotherapies

Disqualifiers: Germ cell tumors, Lymphoma, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating brain metastases, which are cancer cells that have spread to the brain from other parts of the body. The aim is to determine if focused radiation therapy, specifically hypofractionated stereotactic radiosurgery, before surgery can delay or prevent the return of these metastases more effectively than current treatments. Individuals with a solid tumor cancer (excluding lymphoma or germ cell tumors) who have a surgically removable brain metastasis and have not received this type of radiation before might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications. However, if you are on cytotoxic chemotherapies, you must stop them 7 days before starting the trial. Other medications will be reviewed individually by the study team.

What prior data suggests that hypofractionated stereotactic radiosurgery is safe?

Research has shown that hypofractionated stereotactic radiosurgery, a type of radiation treatment, is generally safe for treating cancer that has spread to the brain. Studies have found that it effectively controls tumors while minimizing harm to nearby brain areas. As a result, patients often experience symptom relief and good tumor control with manageable side effects. Reports from past research highlight that the treatment is well-tolerated, offering a favorable balance between benefits and risks. This makes it a promising option for patients with brain metastases. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for brain metastases?

Researchers are excited about hypofractionated stereotactic radiosurgery (fSRS) for brain metastases because it targets tumors with high precision and speed. Unlike traditional whole-brain radiation therapy, which can take weeks and affect healthy brain tissue, fSRS delivers concentrated doses directly to the tumor over just three days. This approach minimizes damage to surrounding healthy tissue while potentially allowing for quicker surgical resection and faster recovery times. By combining this precise radiation technique with surgery, researchers hope to improve outcomes and reduce the side effects typically associated with broader radiation treatments.

What evidence suggests that hypofractionated stereotactic radiosurgery is effective for brain metastases?

Research has shown that hypofractionated stereotactic radiosurgery (HySRS), which participants in this trial will receive before resection, effectively treats cancer that has spread to the brain. One study found that this treatment controlled tumor growth in 73% of patients with larger brain tumors after 12 months, compared to 54% with single-fraction radiosurgery. Patients who have used HySRS experienced safe relief from symptoms and better control of tumor growth. The benefits and risks of HySRS make it a good option for standard treatment after surgery for brain metastases. Overall, this approach appears promising for improving outcomes in patients with brain metastases. ^{2 5 6 7 8}

Who Is on the Research Team?

Michael Yu, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with certain solid tumor cancers that have spread to the brain, and are expected to live at least 3 more months. They must have one or more brain tumors suitable for surgery and not previously treated with specific radiosurgery. Participants should be able to undergo MRI scans, not be pregnant or breastfeeding, and willing to use effective contraception.

Inclusion Criteria

I am allowed to receive treatments like immunotherapy or chemotherapy as decided by my doctor.

This study permits the re-enrollment of participant who has discontinued the study due to pre-treatment failure (i.e., the participant has not been treated). If re-enrolled, participant must be re-consented

I can care for myself but may need occasional help.

Exclusion Criteria

Individuals who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

My brain cancer is near the optic nerve.

Participants with active or prior documented inherited hypersensitivity syndromes, certain collagen vascular diseases, and certain autoimmune diseases

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive hypofractionated stereotactic radiosurgery (fSRS) in 9 Gray Units (Gy) per fraction x 3 consecutive daily fractions (27 Gy total) to the index metastasis

3 days

3 visits (in-person)

Surgery

Participants undergo stereotactic craniotomy for surgical resection of the index metastasis

Within 5 days following completion of fSRS

Follow-up

Participants are monitored for local control rate, rate of distant brain recurrence, and development of leptomeningeal disease

up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Hypofractionated Stereotactic Radiosurgery

Trial Overview The study tests if pre-operative hypofractionated stereotactic radiosurgery (a type of focused radiation therapy) followed by surgery can extend the time before a brain tumor starts growing again compared to current treatments.

How Is the Trial Designed?

Group I: Hypofractionated Stereotactic Radiosurgery prior to resection Experimental Treatment 1 Intervention

Participants will be given hypofractionated stereotactic radiosurgery (fSRS) in 9 Gray Units (Gy) per fraction x 3 consecutive daily fractions (27 Gy total) to the index metastasis that will be resected on Days 1-3 (3 consecutive days). If there are additional non index brain metastasis, they will be treated with standard stereotactic radiosurgery at the time of fSRS. Participants will then undergo stereotactic craniotomy for surgical resection of the index metastasis within 5 days following completion of fSRS.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Published Research Related to This Trial

Hypofractionated Gamma Knife radiosurgery is effective for treating large metastatic brain tumors (average volume of 18.3 cm³), achieving a local control rate of 90% and a median survival time of 16.2 months.

The treatment demonstrated low toxicity, with only 8.3% of patients experiencing grade 1 side effects and a single case of radiation necrosis, indicating it is a safe option for patients who cannot undergo surgical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated Stereotactic Gamma Knife Radiosurgery for Large Brain Metastases: A Retrospective, Single Center Study. Kim, JW., Park, HR., Lee, JM., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9014302/

Outcomes of Hypofractionated Stereotactic Radiotherapy ... The risk of radionecrosis at 12 months was 7.1% for all lesions, 13.2% for lesions >1 cm, and 3.2% for lesions ≤1 cm (p = 0.15). Conclusions. FSRT is safe and ...

2. mdpi.com mdpi.com/2072-6694/17/18/3026

Hypo-Fractionated Stereotactic Radiosurgery for the ... The 12-month local control rates for brain metastases ≥3 cm were 54% after single-fraction SRS and 73% after HySRS (p = 0.02). The 1-year cumulative incidence ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2214751922001372

Clinical outcomes of Hypofractionated stereotactic ... Treatment with HFSRT for larger brain metastases using a similar dose-fractionation schedule was deemed safe and effective in symptom relief and tumor control.

4. academic.oup.com academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noaf182/8220627

Results of the ESTRON randomized phase 2 trial | Neuro ... The favorable risk-benefit profile of HFSRT supports its use as a safe and effective standard-of-care option following brain metastasis ...

5. practicalradonc.org practicalradonc.org/article/S1879-8500(22)00054-6/fulltext

Radiation Therapy for Brain Metastases: An ASTRO ... As WBRT offers no survival benefit over SRS and worse neurocognitive outcomes, SRS for patients with up to 4 intact brain metastases and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12468168/

Hypo-Fractionated Stereotactic Radiosurgery for the ... This technique maintains high tumor control while minimizing radiation toxicity to nearby brain structures. This review summarizes the current ...

7. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.869572/full

Outcomes of Hypofractionated Stereotactic Radiotherapy ... Conclusions: FSRT is safe and effective in the treatment of brain metastases of any size with excellent local control and toxicity outcomes. Prospective ...

8. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2771754

Multi-institutional Analysis of Prognostic Factors and ... The results of this study suggest that hypofractionated stereotactic radiotherapy has a favorable risk-benefit profile and, compared with whole-brain ...