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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special type of radiation therapy called stereotactic radiosurgery to evaluate its effectiveness in treating melanoma that has spread to more than three places in the brain. The treatment targets tumors with a high dose of radiation while minimizing harm to surrounding healthy tissue. It suits individuals with confirmed melanoma and multiple brain metastases. Participants must safely pause blood-thinning medications around the time of treatment and have a recent MRI showing more than three brain tumors. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to important advancements in melanoma care.

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 prior data suggests that stereotactic radiosurgery is safe for treating melanoma brain metastases?

Research has shown that stereotactic radiosurgery (SRS) is generally well-tolerated by patients with brain tumors, including those from melanoma. Studies indicate that SRS precisely targets tumors with high doses of radiation while protecting the surrounding healthy brain tissue.

One study found that most patients experienced only mild side effects, such as headaches or tiredness, after treatment, with serious side effects being rare. Another study reviewed the safety of SRS and concluded that it is a safe option for treating multiple brain tumors.

Overall, evidence suggests that SRS is a safe treatment choice for individuals with melanoma that has spread to the brain. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Stereotactic Radiosurgery (SRS) is unique because it targets melanoma brain metastases with extreme precision, delivering high doses of radiation directly to the tumor while sparing surrounding healthy brain tissue. Unlike traditional whole-brain radiation therapy, which can affect both cancerous and healthy cells, SRS focuses solely on the tumor, reducing potential side effects. Researchers are excited about SRS because it offers a non-invasive option that can be completed in a single day, potentially leading to quicker recovery times and improved quality of life for patients.

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

Studies have shown that stereotactic radiosurgery (SRS) effectively treats brain tumors that have spread from other parts of the body, such as melanoma. SRS delivers a high dose of radiation directly to the tumor, targeting the cancer while protecting healthy tissue. Research indicates that SRS is a well-established treatment for these brain tumors and is often considered alongside surgery. Tumors up to 3 cm in size may respond well to this treatment. While SRS is generally effective, its success can vary based on factors like the tumor's size and location. Participants in this trial will undergo SRS as part of the study. ^{1 4 5 6 7}

Who Is on the Research Team?

Jing Li

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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 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 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8390419/

Outcomes after stereotactic radiosurgery of brain metastases ... We analyzed outcomes of SRS with a particular focus on the graded prognostic assessment (GPA, melanoma molGPA), prognostic factors, and toxicity.

2. nature.com nature.com/articles/s41467-024-47998-8

Response of treatment-naive brain metastases to ... Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone

3. surgicalneurologyint.com surgicalneurologyint.com/surgicalint-articles/stereotactic-radiosurgery-for-brain-metastases-from-malignant-melanoma/

Stereotactic radiosurgery for brain metastases from ... Surgical resection and stereotactic radiosurgery (SRS) are well-established treatment methods for patients with brain metastases.

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

Radiation Therapy for Brain Metastases: An ASTRO ... A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung ...

5. link.springer.com link.springer.com/article/10.1007/s11864-024-01289-y

The Role of Radiotherapy in the Management ... Radiation therapy (whole brain radiotherapy- WBRT and stereotactic radiosurgery- SRS) is an integral part of treating melanoma brain metastases.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10670108/

Stereotactic Radiosurgery of Multiple Brain Metastases Local treatments like stereotactic radiosurgery, a precise way of using radiation to treat tumors, are important for addressing brain metastases.

7. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2835449

Therapy, Safety, and Logistics of Preoperative vs ... This randomized clinical trial evaluates preoperative stereotactic radiation therapy logistics and safety profile compared with ...