Radiation Therapy for Melanoma

(MelPORT Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Devarati Mitra, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if adding radiation to lymph nodes along with immune-boosting medicine helps prevent cancer from coming back in patients with a specific type of skin cancer. It focuses on patients who have a high risk of their cancer spreading to their lymph nodes and are already planned to receive immunotherapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves radiation therapy and immunotherapy, it's important to discuss your current medications with the trial team to ensure there are no interactions.

What data supports the idea that Radiation Therapy for Melanoma is an effective treatment?

The available research shows that combining radiation therapy with immunotherapy can be effective for treating melanoma, especially in cases where other treatments have failed. Studies indicate that radiation therapy can help the immune system better recognize and attack cancer cells, potentially improving the overall response to treatment. For example, one study found that using radiation therapy alongside immunotherapy helped patients who did not respond to a drug called nivolumab. Another study highlighted that this combination could be safe and might improve survival outcomes, although more research is needed to confirm these findings. Overall, radiation therapy appears to be a promising option, especially for advanced melanoma cases. ^{1 2 3 4 5}

What safety data is available for radiation therapy in treating melanoma?

Safety data for radiation therapy in treating melanoma includes studies on the combination of immune checkpoint inhibitors and palliative radiotherapy, which focus on immune-related adverse events. Anti-PD-1 therapies, such as nivolumab and pembrolizumab, are generally better tolerated than conventional treatments but can still cause mild to severe immune-related adverse events. The safety of combined immunotherapy and thoracic radiation therapy has been evaluated in phase 1/2 trials, and a phase 1 trial has assessed the safety of ipilimumab with stereotactic body radiation therapy in metastatic melanoma. Overall, while many adverse events are mild and manageable, there is a need for further understanding and prevention of severe adverse events. ^{4 6 7 8 9}

Is the treatment Immunotherapy promising for melanoma when combined with radiation therapy?

Yes, combining immunotherapy with radiation therapy for melanoma is promising. Studies show that this combination can enhance the body's immune response against cancer, potentially improving treatment outcomes. This approach has shown positive results in clinical trials and is considered a safe and effective option for treating melanoma. ^{5 10 11 12 13}

Research Team

Devarati Mitra, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with high-risk melanoma that's spread to sentinel lymph nodes but not elsewhere, who haven't had all their affected lymph nodes removed and are set for immunotherapy. They should be fairly active (ECOG ≤3), able to follow up, have a life expectancy over 6 months, and use contraception if capable of childbearing.

Inclusion Criteria

I can take care of myself but cannot do heavy physical work.

There are no signs that lymph nodes are affected before a sentinel lymph node biopsy.

My cancer has not spread to distant parts of my body.

Exclusion Criteria

I am an adult who can make my own medical decisions, not pregnant, and not incarcerated.

I have had all lymph nodes removed where cancer was found.

My cancer has spread to distant parts of my body.

Treatment Details

Interventions

• Immunotherapy (Immunotherapy)
• Quality-of-Life Assessment (Other)
• Radiation Therapy (Radiation Therapy)

Trial Overview The study is testing whether radiation therapy on the lymph nodes after a biopsy can lower the chance of cancer returning in those nodes for patients with high-risk melanoma starting immunotherapy, without removing more lymph nodes.

Participant Groups

Group I: Group I (immunotherapy, radiation therapy) Experimental Treatment 3 Interventions

Within 12 weeks of SLNB, patients start nodal radiation therapy (30 Gy in 5 treatments over 2-2.5 weeks). Immunotherapy planned to begin at any time after SLNB.

Group II: Group II (immunotherapy) Active Control 2 Interventions

Patients planned to undergo immunotherapy.

Immunotherapy is already approved in Canada for the following indications:

Approved in Canada as Various Immunotherapies for:

• Melanoma
• Non-Hodgkin lymphoma
• Chronic myelogenous leukemia (CML)
• Kidney cancer
• Breast cancer
• Prostate cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

Findings from Research

The combination of localized radiotherapy and immune checkpoint inhibitors, like pembrolizumab, may enhance the immune response against tumors, particularly in metastatic melanoma, but clinical data on this combination is limited.

A case report indicates that pembrolizumab may cause acute skin radiosensitization when used with radiation therapy, suggesting a rapid interaction that warrants caution in prescribing this combination for advanced cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute skin reaction suggestive of pembrolizumab-induced radiosensitization. Sibaud, V., David, I., Lamant, L., et al.[2015]

Radiotherapy (RT) may enhance the effectiveness of immunotherapy (IO) in treating metastatic melanoma by modifying the tumor microenvironment and improving the immune response, especially in patients who have shown resistance to IO alone.

The study aims to assess the overall treatment response and safety of combining RT with IO in patients with progressive metastatic melanoma, highlighting a potential strategy to overcome treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can radiation restore immunotherapy response in metastatic melanoma refractory to checkpoint inhibitors: An institutional experience in salvaging immunotherapy resistant disease. Alhumaid, M., Dinakaran, D., Smylie, M., et al.[2023]

Concurrent immunoradiotherapy, combining immune checkpoint inhibitors with radiotherapy, showed a 30% overall response rate in 16 patients with metastatic melanoma who had progressed on nivolumab, with a notable 68.8% response rate in lesions within the radiation fields.

Nivolumab combined with radiotherapy demonstrated a 100% response rate inside the radiation fields, suggesting it may be more effective than ipilimumab in this setting, although some patients experienced grade 3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. Nomura, M., Otsuka, A., Yoshimura, M., et al.[2019]

In a phase 1 trial with 13 patients suffering from metastatic melanoma, the combination of ipilimumab and high-dose radiation therapy was found to be feasible and safe, with 25% of patients experiencing grade 3 or 4 adverse events.

Local control of the treated lesions was achieved in 11 out of 12 patients, and while only 3 patients showed clinical benefit in non-irradiated lesions, the results suggest that early radiation therapy may enhance the effectiveness of ipilimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Dose Escalation Trial of Ipilimumab and Stereotactic Body Radiation Therapy in Metastatic Melanoma. Sundahl, N., De Wolf, K., Kruse, V., et al.[2019]

Combining radiotherapy with immunotherapy for melanoma can enhance the immune response by increasing tumor visibility to T cells, making it a promising treatment strategy, especially for advanced cases.

This combination therapy appears to be safe and shows potential for improved survival outcomes, but more prospective studies are needed to solidify these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and radiotherapy in melanoma: a multidisciplinary comprehensive review. Tagliaferri, L., Lancellotta, V., Fionda, B., et al.[2022]

A study of 105 patients with advanced melanoma or lung cancer revealed significant gaps in their understanding of immunotherapy, particularly regarding how it works and the potential side effects.

One-third of participants mistakenly believed that the primary goal of their immunotherapy treatment was to cure their cancer, highlighting the need for better patient education about treatment expectations and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Knowledge About Risks, Benefits, and Curative Potential of Immunotherapy Among Patients with Advanced Cancer. Petrillo, LA., Zhou, AZ., Sullivan, R., et al.[2021]

Immunotherapies, particularly anti-PD-1 checkpoint inhibitors like nivolumab and pembrolizumab, have significantly improved survival rates for metastatic melanoma patients while being less toxic than traditional treatments.

Despite their better tolerability, anti-PD-1 therapies can still cause a range of immune-related adverse events, most of which are mild, but there is a pressing need to understand and manage severe side effects due to the increased life expectancy of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of anti PD-1 therapeutics for the treatment of melanoma. Ramelyte, E., Schindler, SA., Dummer, R.[2018]

In a study of 60 patients receiving combined immunotherapy and thoracic radiation therapy (iRT), no patients experienced severe grade ≥4 toxicities, indicating a favorable safety profile for this treatment approach.

While some patients did experience grade 3 toxicities, particularly pulmonary and hematologic issues, the overall short-term safety of iRT suggests it can be administered without significant risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. Verma, V., Cushman, TR., Selek, U., et al.[2022]

Combining palliative radiotherapy (pRT) with immune checkpoint inhibitors (ICI) in melanoma treatment significantly improved objective response rates, complete response rates, and one-year local control, indicating enhanced efficacy of the treatment.

The combination treatment did not lead to a significant increase in adverse events or immune-related adverse events compared to ICI alone, suggesting that it is a safe option for patients with advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of immune checkpoint inhibitors in combination with palliative radiotherapy in advanced melanoma: A systematic review. Ben Shimol, J., Guzman-Prado, Y., Karlinskaya, M., et al.[2021]

Radiation therapy (RT) is crucial for controlling non-small cell lung cancer (NSCLC), but it often fails to prevent distant metastases, leading to poor patient outcomes.

Recent advancements in combining RT with immune checkpoint blockade immunotherapy show promise in enhancing systemic anti-tumor responses in NSCLC, similar to successful strategies seen in melanoma, with ongoing clinical trials exploring this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experiences of combining immunotherapy and radiation therapy in non-small cell lung cancer: lessons from melanoma. Kalbasi, A., Rengan, R.[2020]

Combining immune checkpoint inhibitors (ICI) with radiotherapy (RT) shows promise in enhancing anti-melanoma activity, potentially improving responses in both targeted and non-targeted lesions, based on preclinical and preliminary clinical findings.

Current evidence from retrospective studies and a few prospective trials suggests a synergistic effect between RT and ICI for treating metastatic melanoma, with ongoing trials aimed at confirming these initial observations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and immune checkpoints inhibitors for advanced melanoma. Filippi, AR., Fava, P., Badellino, S., et al.[2018]

Recent studies indicate that combining radiation therapy with immunotherapy can enhance treatment outcomes for melanoma, suggesting a beneficial interaction between the two approaches.

Clinical evidence, including case studies and pilot studies, shows that this combination may improve efficacy, although some treatments may also increase toxicity, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. Barker, CA., Postow, MA.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Acute skin reaction suggestive of pembrolizumab-induced radiosensitization. [2015]

2. Ireland pubmed.ncbi.nlm.nih.gov

Can radiation restore immunotherapy response in metastatic melanoma refractory to checkpoint inhibitors: An institutional experience in salvaging immunotherapy resistant disease. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of concurrent immunoradiotherapy in patients with metastatic melanoma after progression on nivolumab. [2019]

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

Phase 1 Dose Escalation Trial of Ipilimumab and Stereotactic Body Radiation Therapy in Metastatic Melanoma. [2019]

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

Immunotherapy and radiotherapy in melanoma: a multidisciplinary comprehensive review. [2022]

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

Knowledge About Risks, Benefits, and Curative Potential of Immunotherapy Among Patients with Advanced Cancer. [2021]

7. England pubmed.ncbi.nlm.nih.gov

The safety of anti PD-1 therapeutics for the treatment of melanoma. [2018]

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

Safety of Combined Immunotherapy and Thoracic Radiation Therapy: Analysis of 3 Single-Institutional Phase I/II Trials. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of immune checkpoint inhibitors in combination with palliative radiotherapy in advanced melanoma: A systematic review. [2021]

10. China pubmed.ncbi.nlm.nih.gov

Clinical experiences of combining immunotherapy and radiation therapy in non-small cell lung cancer: lessons from melanoma. [2020]

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

Combining radiation and immunotherapy for synergistic antitumor therapy. [2021]

12. Ireland pubmed.ncbi.nlm.nih.gov

Radiotherapy and immune checkpoints inhibitors for advanced melanoma. [2018]

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

Combinations of radiation therapy and immunotherapy for melanoma: a review of clinical outcomes. [2021]