Radiation Therapy for Melanoma

(MelPORT Trial)

Recruiting at 2 trial locations

Overseen By Devarati Mitra, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Immunotherapy

Disqualifiers: Distant metastasis, Previous radiation, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2-2.5 weeks for radiation therapy; immunotherapy duration not specified

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding radiation therapy to immunotherapy (a type of biological therapy) can help prevent melanoma (a type of skin cancer) from returning in patients with certain high-risk features. It specifically targets patients whose cancer has spread to nearby lymph nodes but not to distant parts of the body. Participants will receive either both immunotherapy and radiation or just immunotherapy. Those who have had a sentinel lymph node biopsy showing high-risk melanoma and are set to start immunotherapy without a full lymph node removal might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that immunotherapy offers promising results for melanoma patients. In one study, 7.2% of patients experienced serious immune-related side effects, and 2.8% had to stop treatment due to these effects. However, immunotherapy can extend patients' lives and reduce the likelihood of melanoma returning after surgery.

Radiation therapy is another option for treating melanoma, despite the cancer's resistance to radiation. Studies indicate that radiation therapy is generally safe, with most side effects being manageable. Only about 3% of patients experienced serious side effects.

Overall, both treatments are generally safe, but they can cause serious side effects in some cases. Considering these risks is important before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for melanoma, which typically involve surgery, chemotherapy, or standalone immunotherapy, this new approach combines immunotherapy with radiation therapy. Researchers are excited about this combination because radiation can potentially enhance the effectiveness of immunotherapy by increasing the immune system's ability to recognize and attack cancer cells. This integrated method aims to not only improve the body's immune response but also target the cancer more precisely, possibly leading to better outcomes and fewer side effects compared to traditional options.

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

In this trial, participants in Group I will receive both immunotherapy and radiation therapy. Research has shown that combining these treatments might benefit melanoma patients more than using just one. One study found that 83.3% of patients receiving both treatments were cancer-free after 12 months, compared to 66.7% of those who only received immunotherapy, which is the treatment for Group II in this trial. This combination works because radiation can enhance the immune system's ability to locate and attack cancer cells. Additionally, 39.1% of patients responded to the combined treatment, with some experiencing tumor shrinkage or disappearance. These results suggest that using both treatments together might be more effective in preventing cancer recurrence in some cases. ^{6 7 8 9 10}

Who Is on the Research Team?

Devarati Mitra, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 have had all lymph nodes removed where cancer was found.

My cancer has spread to distant parts of my body.

I am currently pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive adjuvant immunotherapy and nodal radiation therapy (30 Gy in 5 treatments over 2-2.5 weeks) or adjuvant immunotherapy alone

2-2.5 weeks for radiation therapy; immunotherapy duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments for regional nodal recurrence, locoregional recurrence, distant metastasis, long-term toxicity, and quality of life

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Immunotherapy
• Quality-of-Life Assessment
• 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.

How Is the Trial Designed?

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 European Union, United States, Canada for the following indications:

Approved in European Union as Various Immunotherapies for:

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

Approved in United States as Various Immunotherapies for:

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

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

Combining radiation therapy with immunotherapy shows great potential for enhancing cancer treatment, as preclinical studies suggest that radiation can make tumor cells more vulnerable to immune attacks.

Clinical trials have begun to support the idea that this combination can effectively boost antitumor immune responses, with ongoing studies exploring various therapeutic vaccines alongside radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining radiation and immunotherapy for synergistic antitumor therapy. Ferrara, TA., Hodge, JW., Gulley, JL.[2021]

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