Stereotactic Radiosurgery for Brain Metastasis

Recruiting at 6 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Disqualifiers: Whole brain radiation, Brainstem metastasis, Leptomeningeal metastasis, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Varies based on treatment arm

69 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of delivering stereotactic radiosurgery, a precise radiation therapy, for brain tumors that have spread from other body parts. It seeks to determine if a single high-dose treatment better controls tumors and side effects compared to multiple sessions. The trial seeks participants with brain metastases between 2 and 4 cm in size who have not previously received radiosurgery. It may suit individuals with cancer that has spread to the brain and who can undergo MRIs with contrast. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that stereotactic radiosurgery is safe for treating brain metastasis?

Research shows that single-session stereotactic radiosurgery (SRS) generally treats brain tumors that have spread with good tolerance. Studies have found that keeping the treatment area within certain limits manages the risks effectively. Additionally, fractionated SRS, which divides the treatment into smaller doses, is safe, particularly for larger tumors. Both methods have been studied and found effective, with efforts to minimize side effects. Overall, while risks exist, both single and fractionated SRS have been tested and are considered safe for treating brain tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about stereotactic radiosurgery (SRS) for brain metastasis because it offers a precise and targeted approach that minimizes damage to surrounding healthy brain tissue. Unlike traditional whole-brain radiation therapy, which can affect large areas of the brain, SRS focuses high doses of radiation directly at the tumor site, reducing potential side effects and preserving cognitive function. Additionally, the trial compares single fraction SRS, where treatment is delivered in one session, with fractionated SRS, which spreads treatment over several sessions. This comparison aims to determine the best balance between effectiveness and safety, potentially leading to more personalized treatment options for patients.

What evidence suggests that this trial's treatments could be effective for brain metastasis?

This trial compares two approaches to stereotactic radiosurgery (SRS) for brain metastasis. Research has shown that single-session SRS, which participants in Arm A will receive, can effectively target brain tumors with high-energy radiation, though it may pose a risk of serious nerve damage. A review of studies found that while single-session SRS can control brain tumors, side effects must be considered. Alternatively, participants in Arm B will undergo fractionated stereotactic radiosurgery, which spreads the treatment over several smaller sessions. This method is also effective and usually results in fewer severe side effects. Studies have reported good survival rates with fractionated SRS, showing high tumor control rates at 6 and 12 months. Both methods offer advantages and disadvantages, and the choice often involves weighing effectiveness against potential side effects. ^{1 2 5 6 7}

Who Is on the Research Team?

Paul D. Brown, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with cancer that has spread to the brain from another body part, like lung or breast. Participants must have at least one tumor in the brain between 2.0 and 4.0 cm not previously treated with radiosurgery, be able to undergo MRI scans, and have a certain level of physical function (KPS >= 50 or ECOG PS >= 2). Pregnant women and those who've had whole-brain radiation or specific large brainstem metastases are excluded.

Inclusion Criteria

I have a tumor in my brain between 2.0 and 4.0 cm that hasn't been treated with radiosurgery.

My cancer has spread to my brain from another part of my body.

I've had radiosurgery or surgery without cancer growth in those areas. No repeat treatment in the same spot.

Exclusion Criteria

I have had whole brain radiation before.

My cancer has spread to the lining of my brain and spinal cord.

I have a brain tumor larger than 4 cm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo either single fraction SRS or fractionated SRS

Varies based on treatment arm

Multiple visits for treatment sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up at 3 months, every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Stereotactic Radiosurgery

Trial Overview The FRACTIONATE trial is comparing two types of stereotactic radiosurgery (SRS) for treating brain tumors: single fraction SRS delivers treatment in one session while fractionated SRS spreads it over multiple sessions. The goal is to see which method better controls the tumor growth and side effects.

How Is the Trial Designed?

Group I: Arm B (fractionated SRS) Experimental Treatment 3 Interventions

Patients undergo fractionated SRS.

Group II: Arm A (single fraction SRS) Experimental Treatment 3 Interventions

Patients undergo single fraction SRS.

Stereotactic Radiosurgery is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Approved in United States as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas
• Liver tumors
• Lung tumors
• Spinal cord tumors

Approved in Canada as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Approved in Japan as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Approved in China as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Approved in Switzerland as Stereotactic Radiosurgery for:

• Brain tumors
• Metastatic brain tumors
• Arteriovenous malformations (AVMs)
• Trigeminal neuralgia
• Acoustic neuromas

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Radiosurgery (SRS) using a mono-isocentric, non-coplanar technique effectively treated 172 patients with multiple brain metastases, achieving a 2-year local progression-free survival (LPFS) rate of 71.6%.

The study indicates that higher biological effective doses (BED) correlate with better local control, and the technique allows for safe treatment of patients with many metastases while delaying the need for whole-brain radiation therapy (WBRT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term disease outcome and volume-based decision strategy in a large cohort of multiple brain metastases treated with a mono-isocentric linac-based Stereotactic Radiosurgery technique. Alongi, F., Nicosia, L., Figlia, V., et al.[2021]

Stereotactic radiosurgery (SRS) using CyberKnife is a safe and effective treatment for elderly patients (≥65 years) with brain metastases, achieving high local control rates and maintaining a stable quality of life in 97.9% of patients.

In a study of 97 patients, SRS demonstrated a 79% overall survival rate at 3 months and a 99.2% local tumor progression-free rate at 6 months, indicating its efficacy compared to traditional whole brain radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation. Acker, G., Hashemi, SM., Fuellhase, J., et al.[2021]

In a study of 51 patients treated with stereotactic radiosurgery (SRS) for brain metastases, the median survival time was 15 months, indicating that SRS is an effective treatment option.

Patients without active extracranial disease had significantly longer survival compared to those with active disease, highlighting the importance of managing systemic disease for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery for the treatment of brain metastases; results from a single institution experience. Burke, D., Mascott, C., Rock, L., et al.[2021]

Stereotactic radiosurgery is a valuable treatment option for both intracranial and extracranial lesions, often used alongside surgery, conventional radiation, and chemotherapy.

The review highlights the evolution and variety of stereotactic radiosurgery machines, including the Gamma Knife, indicating a growing range of technologies available for effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delivery of stereotactic radiosurgery: a cross-platform comparison. Nguyen, T., Hsu, W., Lim, M., et al.[2011]

Moderately dosed stereotactic radiosurgery (SRS) for one to four brain metastases showed a median overall survival of 7.5 months, with high local brain control rates of 87% at 6 months and 79% at 12 months, indicating its efficacy in treating limited brain metastases.

The study suggests that initial SRS alone can be a safe treatment option, as only 22% of patients required additional whole-brain radiotherapy, and significant predictors of survival included the time between the primary diagnosis and brain metastases, as well as the volume of the treated metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. Meisner, J., Meyer, A., Polivka, B., et al.[2021]

CyberKnife stereotactic ablative radiotherapy (SABR) for treating intermediate- to very-high-risk prostate cancer showed a high 3-year biochemical relapse-free survival rate of 90.2%, indicating its efficacy in managing this condition.

The treatment was well-tolerated, with no patients experiencing severe toxicity (≥ grade 3), and only mild genitourinary and gastrointestinal side effects were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. Fan, CY., Chao, HL., Huang, WY., et al.[2017]

Stereotactic radiosurgery (SRS) using CyberKnife for large brain metastasis cavities (≥2 cm) showed a local failure rate of 24%, indicating it can effectively control local disease after surgery.

Patients with synchronous metastases had a higher risk of distant brain failure, suggesting that while SRS can delay the need for whole brain radiation therapy (WBRT), careful monitoring is needed for those with multiple metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial control after Cyberknife radiosurgery to the resection bed for large brain metastases. Vogel, J., Ojerholm, E., Hollander, A., et al.[2018]

Stereotactic radiosurgery (SRS) is an effective treatment for patients with brain metastases, particularly prolonging survival for those with a single metastasis and maintaining functional independence for patients with up to three metastases.

As SRS technology becomes more widely used, careful patient selection and treatment planning are essential to maximize its benefits and integrate it safely with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in intracranial stereotactic radiotherapy for metastases. Pinkham, MB., Whitfield, GA., Brada, M.[2022]

The combination of stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) improves local tumor control and neurological function in patients with brain metastases, particularly benefiting those with a single metastasis, as it is associated with better survival compared to WBRT alone.

Current studies on SRS compared to other treatments like WBRT or neurosurgery show limited quality and inconclusive evidence, highlighting the need for more rigorous research to assess the effectiveness and safety of these interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical and health economic assessment of radiosurgery for the treatment of brain metastasis. Müller-Riemenschneider, F., Schwarzbach, C., Bockelbrink, A., et al.[2021]

In a study of 130 patients treated with CyberKnife Radiosurgery for brain metastases, a cumulative tumor volume greater than 7cc was linked to worse outcomes, including higher rates of death and neurological defects.

The addition of whole brain radiation therapy (WBRT) was associated with improved survival rates in patients with a higher tumor burden, suggesting that WBRT may play a beneficial role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative volumetric analysis as a key criterion for the treatment of brain metastases. Kim, IK., Starke, RM., McRae, DA., et al.[2018]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

Stereotactic radiosurgery (SRS) for patients with 5 or more melanoma brain metastases showed a high local control rate of 91.3% at 6 months and 82.2% at 12 months, indicating its effectiveness as a treatment option.

The study found that a larger planning target volume (PTV) was a significant predictor of local failure, highlighting the importance of careful treatment planning in achieving better outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases. Frakes, JM., Figura, NB., Ahmed, KA., et al.[2016]

In a study of 4,327 patients with brain metastases from non-small cell lung cancer, it was found that treatment at non-academic facilities significantly increased the likelihood of receiving LINAC SRS over Gamma Knife SRS, especially in the Midwestern, Northeastern, and Southern US regions.

Patients receiving higher doses of radiation (18-24 Gy) were also more likely to receive LINAC SRS, and those living within 20 miles of a treatment facility had a 27% higher chance of receiving LINAC, suggesting that geographic accessibility plays a role in treatment modality choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of linear accelerator versus Gamma Knife stereotactic radiosurgery use for brain metastases in the United States. McClelland Iii, S., Degnin, C., Chen, Y., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4630352/

Efficacy and Safety of Fractionated Stereotactic Radiosurgery ... The median OS was 16 months, and the estimated OS rates at 6, 12 and 18 months were 81.1%, 56.8%, and 40.7%, respectively. Of 21 patients who died, 10 (47.6%) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10772598/

CyberKnife-based stereotactic radiosurgery or fractionated ... CK-based SRS/FSRT is a safe and efficient option for older patients with BM arising from NSCLC, showing good OS without severe side effects.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0936655513004688

Fractionated Stereotactic Radiotherapy using CyberKnife ... Overall survival rates were 52 and 31% at 6 and 12 months, respectively. Local tumour control rates of the 102 total brain metastases were 84 and 78% at 6 and ...

4. jkms.org jkms.org/DOIx.php?id=10.3346/jkms.2025.40.e195

Fractionated Gamma Knife Radiosurgery as a Primary ... Following fGKS, tumor and edema volumes continuously reduced for 6–9 months, with median decreases of 78% and 82%, respectively. Tumor volume ...

5. redjournal.org redjournal.org/article/S0360-3016(20)34451-5/fulltext

Tumor Control Probability of Radiosurgery and ... A minimally invasive treatment option for large metastatic brain tumors: Long-term results of two-session gamma knife stereotactic radiosurgery.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10423099/

Comparing Fractionated and Single-Fraction Gamma Knife ... This study aimed to analyze the outcomes of fractionated and single-fraction gamma knife radiosurgery for brain metastases from non-small-cell lung cancer, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1878875023010914

Comparison of Staged Stereotactic Radiosurgery and ... SSRS and FSRT were found to be comparable for treating brain metastases >2 cm not previously irradiated. Given the paucity of such studies, trials directly ...