Stereotactic Radiosurgery for Melanoma Brain Metastases

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Whole brain radiotherapy, Metastatic cancer, 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: 1

Duration: 1 day

49 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well stereotactic radiosurgery works in treating patients with melanoma that has spread to more than 3 places in the brain. 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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must be able to stop anticoagulation or antiplatelet medications for at least 24 hours before and after the radiosurgery treatment. You can continue other systemic therapies like temozolomide if your oncologist agrees.

What data supports the effectiveness of the treatment Stereotactic Radiosurgery for Melanoma Brain Metastases?

Research shows that stereotactic radiosurgery (SRS) can be effective for treating melanoma brain metastases, especially in patients with multiple lesions. It is also noted that SRS can improve survival when added to whole-brain radiation therapy (WBRT) for brain metastases, and in some cases, it can be used alone to avoid WBRT without reducing survival time. ^{1 2 3 4 5}

Is stereotactic radiosurgery (SRS) safe for treating brain metastases?

Stereotactic radiosurgery (SRS), including methods like CyberKnife and LINAC, has been used safely in treating brain metastases, with studies showing it can reduce neurotoxicity (damage to the nervous system) compared to whole brain radiation therapy. However, some serious complications have been reported, and strategies to reduce these risks are important. ^{2 6 7 8 9}

How is stereotactic radiosurgery different from other treatments for melanoma brain metastases?

Stereotactic radiosurgery (SRS) is unique because it delivers a single, highly focused dose of radiation to precisely target brain metastases, minimizing damage to surrounding healthy tissue. Unlike traditional surgery, it is non-invasive and can be used for patients with multiple brain lesions, offering an alternative to whole-brain radiation therapy. ^{2 3 10 11 12}

Research Team

Jing Li

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for melanoma patients with more than three brain metastases confirmed by MRI. They must have normal kidney function, blood platelet count, and coagulation levels; be able to pause certain medications around treatment time; and not be pregnant or breastfeeding. Patients previously treated with whole-brain radiotherapy or those with additional cancers are excluded.

Inclusion Criteria

Your platelet count is higher than 50,000.

My melanoma diagnosis was confirmed through tissue examination.

All my cancer lesions can be treated, as confirmed by a radiation oncologist.

Exclusion Criteria

I have not had whole brain radiotherapy in the last 3 months.

I do not have cancer spread to the lining of my brain or spinal cord.

You cannot have had an allergic reaction to gadolinium in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo stereotactic radiosurgery (SRS) on day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for local control and neurocognitive preservation at 1, 4, 6, 9, and 12 months post-treatment

12 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Stereotactic Radiosurgery

Trial Overview The study tests stereotactic radiosurgery's effectiveness on patients with multiple melanoma brain metastases. This precise radiation therapy targets tumors directly in a single high dose, potentially sparing healthy tissue.

Participant Groups

Group I: Treatment (SRS) Experimental Treatment 3 Interventions

Patients undergo SRS on day 1.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Stereotactic radiosurgery (SRS) is an effective non-invasive technique for targeting deep brain lesions with high doses of radiation, but it does not provide benefits for newly diagnosed malignant gliomas.

For patients with brain metastases, SRS can improve median survival when combined with whole-brain radiation therapy (WBRT), and in some cases, SRS alone may be a viable treatment option without compromising survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of radiosurgery in the management of malignant brain tumors. Stieber, VW., Ellis, TL.[2019]

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) 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]

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]

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]

Stereotactic ablative radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Local control of melanoma brain metastases treated with stereotactic radiosurgery. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

The role of radiosurgery in the management of malignant brain tumors. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Intracranial control after Cyberknife radiosurgery to the resection bed for large brain metastases. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation. [2021]

7. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Medical and health economic assessment of radiosurgery for the treatment of brain metastasis. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Delivery of stereotactic radiosurgery: a cross-platform comparison. [2011]

12. Germany pubmed.ncbi.nlm.nih.gov

Linac-based radiosurgery of cerebral melanoma metastases. Analysis of 122 metastases treated in 64 patients. [2021]