Pre-Operative Radiotherapy for Sinonasal Melanoma

Overseen By Debarati Mitra, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Immunotherapy

Disqualifiers: Previous radiation, Metastatic disease, Pregnancy, 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

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical research study is to learn if pre-operative radiation therapy can help patients with sinonasal melanoma have better outcomes

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since the trial involves combination immunotherapy, it's best to discuss your current medications with the study team to ensure there are no interactions.

What data supports the effectiveness of this treatment for sinonasal melanoma?

The research suggests that combining surgery with chemotherapy or immunotherapy may improve survival for patients with sinonasal melanoma, while adding radiation therapy to surgery does not significantly increase survival. ^{1 2 3 4 5}

Is pre-operative radiotherapy for sinonasal melanoma safe?

The safety of radiotherapy for sinonasal melanoma has been studied, often used after surgery to help control the disease. While the focus is on its effectiveness, radiotherapy is generally considered safe, but it can have side effects like skin irritation and fatigue. ^{1 4 5 6 7}

How is pre-operative radiotherapy with immunotherapy different for sinonasal melanoma?

This treatment is unique because it combines pre-operative radiotherapy (radiation given before surgery) with immunotherapy (a treatment that helps the immune system fight cancer), which is not commonly used together for sinonasal melanoma. This approach aims to shrink the tumor before surgery and boost the body's immune response, potentially improving outcomes compared to traditional methods like surgery alone or post-operative radiotherapy. ^{1 4 5 6 8}

Research Team

Devarati Mitra, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults over 18 with sinonasal melanoma that can be seen on exams or imaging, and who are considered operable by a surgeon. They must agree to use contraception and have no distant metastasis. It's not for those previously treated with radiation in the nasal area, pregnant women, or anyone under 18.

Inclusion Criteria

I am 18 years old or older.

I have another cancer, but it won't affect my participation in this study.

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

Exclusion Criteria

I have had radiation therapy to my nose or sinus area.

My cancer has spread to other parts of my body.

I am not pregnant, as the treatment could harm an unborn baby.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Immunotherapy

Participants receive neoadjuvant combination immunotherapy

4-6 weeks

Radiation Therapy

Participants receive pre-operative radiation therapy

2-4 weeks

Surgical Resection

Participants undergo surgical resection of the tumor

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Immunotherapy
• Pre-Operative Radiotherapy
• Surgical resection

Trial Overview The PRISM study tests if pre-operative radiation therapy improves outcomes for patients undergoing surgery for sinonasal melanoma. Participants will also receive combination immunotherapy (like ipilimumab and nivolumab) as part of their treatment plan.

Participant Groups

Group I: Surgical resection Experimental Treatment 1 Intervention

Patients will have surgical resection after receiving neodjuvant combination immunotherapy followed by radiation therapy.

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+

Findings from Research

Post-operative radiotherapy significantly improved the three-year overall survival rate for patients with sinonasal malignant melanoma compared to surgery alone, with a p-value of 0.02.

While radiotherapy showed a borderline significant benefit for five-year overall survival (p = 0.05), it did not demonstrate any advantages in disease-free survival or local control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgery alone versus post-operative radiotherapy for sinonasal malignant melanoma: a meta-analysis. Hu, R., Yang, BB.[2019]

A meta-analysis of 423 patients with sinonasal melanoma indicated that combining surgery with chemotherapy significantly improves survival compared to surgery alone or chemotherapy alone.

Radiation therapy did not show a statistically significant benefit in survival when added to surgery, suggesting that multimodality therapy should focus on chemotherapy or immunotherapy alongside surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival in Sinonasal Melanoma: A Meta-analysis. Gore, MR., Zanation, AM.[2022]

In a study of 6 patients with sinonasal malignant melanoma, those who underwent combined modality therapy (surgery, postoperative radiotherapy, and in some cases, chemotherapy and bioimmunotherapy) had an average survival time of 62.7 months, with 1-year, 3-year, and 5-year survival rates of 100%, 83%, and 67%, respectively.

The results suggest that combined modality therapy is effective for sinonasal malignant melanoma, particularly for operable patients, and that preoperative chemotherapy and bioimmunotherapy can enhance treatment efficacy for those who cannot undergo immediate surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical analysis of 6 cases with sinonasal malignant melanoma]. Ma, R., Li, Y., Li, J., et al.[2023]

In a study of 696 patients with surgically resected sinonasal melanoma, adjuvant radiation therapy (RT) did not show a significant overall survival benefit compared to surgery alone, with median survival times of 25.0 months for surgery only and 28.3 months for those receiving RT.

However, adjuvant RT appeared to be beneficial for patients with stage IVB disease, showing a notable survival improvement (adjusted time ratio of 2.58), while it did not significantly impact survival in patients with earlier stages (IVA and III) or based on margin status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant radiation and survival following surgical resection of sinonasal melanoma. Ajmani, GS., Liederbach, E., Kyrillos, A., et al.[2018]

In a two-year follow-up of a patient with locally advanced sinonasal melanoma, treatment involving surgical resection, postoperative radiotherapy, and chemotherapy achieved local tumor control, but a regional recurrence was noted.

The study supports the use of elective neck dissection and postoperative elective neck radiotherapy in patients with clinically N0 sinonasal melanoma, as it may reduce the risk of late regional recurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary mucosal sinonasal melanoma-Case report and review of the literature. The role of complex treatment-surgery and adjuvant radiotherapy. Marinova, L., Yordanov, K., Sapundgiev, N.[2021]

In a study of 6 patients with sinonasal mucosal melanoma treated with radiotherapy alone, all patients achieved complete remission, indicating that radiotherapy can effectively target this aggressive cancer.

Despite the initial success in achieving remission, the prognosis remains poor, as only one patient survived 5 years without disease, highlighting the high risk of metastasis associated with sinonasal mucosal melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy alone as a method of treatment for sinonasal mucosal melanoma: A report based on six cases and a review of current opinion. Sas-Korczynska, B., Reinfuss, M., Mitus, JW., et al.[2022]

High-dose proton beam therapy (PBT) for sinonasal mucosal melanoma (SMM) showed a 5-year overall survival rate of 51% and a disease-free survival rate of 38% in a study of 20 patients, indicating its potential effectiveness as a treatment option.

The treatment resulted in a 5-year local control rate of 62%, with fewer invasive complications compared to surgery, although some patients experienced significant late toxicities, particularly involving the optic nerve.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose proton beam therapy for sinonasal mucosal malignant melanoma. Fuji, H., Yoshikawa, S., Kasami, M., et al.[2022]

In a study of 704 patients with sinonasal melanoma (SNM), immunotherapy did not show any improvement in overall survival compared to those who did not receive it, indicating that it may not be effective for this type of melanoma.

In contrast, immunotherapy significantly improved overall survival in metastatic cutaneous melanoma, suggesting that the effectiveness of immunotherapy varies greatly between different melanoma types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in sinonasal melanoma: treatment patterns and outcomes compared to cutaneous melanoma. Klebaner, D., Saddawi-Konefka, R., Finegersh, A., et al.[2021]

References

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

Surgery alone versus post-operative radiotherapy for sinonasal malignant melanoma: a meta-analysis. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Survival in Sinonasal Melanoma: A Meta-analysis. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Clinical analysis of 6 cases with sinonasal malignant melanoma]. [2023]

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

Adjuvant radiation and survival following surgical resection of sinonasal melanoma. [2018]

5. Poland pubmed.ncbi.nlm.nih.gov

Primary mucosal sinonasal melanoma-Case report and review of the literature. The role of complex treatment-surgery and adjuvant radiotherapy. [2021]

6. Poland pubmed.ncbi.nlm.nih.gov

Radiotherapy alone as a method of treatment for sinonasal mucosal melanoma: A report based on six cases and a review of current opinion. [2022]

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

High-dose proton beam therapy for sinonasal mucosal malignant melanoma. [2022]

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

Immunotherapy in sinonasal melanoma: treatment patterns and outcomes compared to cutaneous melanoma. [2021]