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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether pre-operative radiation therapy combined with immunotherapy (a type of biological therapy that helps the immune system fight cancer) can improve outcomes for patients with certain types of melanoma. Specifically, it targets those with sinonasal melanoma, affecting the nasal cavity and sinuses, and anorectal melanoma, affecting the anorectal canal. Participants must have a confirmed diagnosis of melanoma in these areas and no signs of cancer spreading elsewhere. The trial focuses on patients undergoing or planning to undergo a combination of immunotherapy treatments. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to advancements in melanoma care.

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.

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

Research has shown that immunotherapy can extend the lives of some patients with sinonasal melanoma. While beneficial, it may also cause side effects such as tiredness and skin reactions, which are usually manageable.

Studies have found that receiving radiotherapy before surgery can improve outcomes. Most patients tolerate it well, though some may experience side effects like skin irritation or fatigue.

Both treatments show promise but carry potential risks. Discussing expectations with healthcare providers is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment for sinonasal and anorectal melanoma because it combines immunotherapy with pre-operative radiotherapy, which is a novel approach compared to the standard of care like surgery, chemotherapy, or standalone radiotherapy. For sinonasal melanoma, the treatment leverages immunotherapy alongside 20 fraction radiation therapy before surgery, potentially enhancing tumor shrinkage and making previously inoperable tumors resectable. In anorectal melanoma, the treatment uses a flexible radiation schedule (5 or 15 fractions) based on the tumor's response to immunotherapy, optimizing the patient's chances of a successful surgical outcome. This dual approach aims to boost the immune system's ability to fight cancer while maximizing the effectiveness of radiation therapy, offering hope for improved patient outcomes.

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

Research has shown that immunotherapy, included in this trial's treatment, can extend the lives of patients with sinonasal melanoma. Studies indicate that about 42.6% of patients survive for 5 years with additional immunotherapy. For anorectal melanoma, immunotherapy, also part of the trial, can shrink tumors, facilitating surgical removal. The trial also tests pre-operative radiotherapy, using radiation before surgery, to potentially improve survival rates for sinonasal melanoma. In some cases, this approach significantly increases the chances of living for 3 years compared to surgery alone. This combination of treatments aims to improve outcomes for patients facing these challenging types of melanoma. ^{1 2 3 4 6}

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

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

I agree to use birth control during the study.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Sinonasal melanoma: patients with sinonasal melanoma Experimental Treatment 1 Intervention

A. Patients with upfront resectable disease Treatment: * Immunotherapy * 20 fraction radiation therapy +/- ongoing immunotherapy * Surgery B. Patients whose disease is not resectable at presentation Treatment: Immunotherapy with potential to enter resectable disease pathway if tumor becomes resectable or continue treatment as per multidisciplinary team preference if tumor does not become resectable

Group II: Anorectal melanoma: patients with anorectal melanoma Experimental Treatment 1 Intervention

A. Patients with disease resectable with a sphincter sparing procedure Treatment: * Immunotherapy * 5 fraction radiation therapy * Surgery B. Patients with disease not resectable with a sphincter sparing procedure Treatment: * Immunotherapy to maximal response * 5 or 15 fraction radiation (depending on immunotherapy response) +/- ongoing immunotherapy * Surgery or biopsy

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

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]

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]

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 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 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 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38686598/

Immunotherapy in the Management of Sinonasal Mucosal ... Six studies reported a combined 5-year OS after adjuvant immunotherapy treatment of 42.6% (95% CI: 39.4-45.8). Thirteen studies encompassing 117 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39782303/

Outcomes of Immunotherapy Treatment in Sinonasal ... Overall survival at 1-, 2-, and 5 years was 86.9%, 74.1%, and 39.1%, respectively. Conclusion: Approximately half of patients will have a local ...

3. journals.sagepub.com journals.sagepub.com/doi/10.1177/19458924241308953

Outcomes of Immunotherapy Treatment in Sinonasal ... Sinonasal mucosal melanoma has poor survival despite multimodality treatment. While the impact of immunotherapy (IT) on metastatic cutaneous ...

4. nature.com nature.com/articles/s41598-023-45705-z

Sinonasal mucosal melanoma treatment response ... Available data from a pooled analysis from clinical trials indicate that efficacy outcomes seem to be poorer in mucosal melanoma compared to ...

5. aao-hnsfjournals.onlinelibrary.wiley.com aao-hnsfjournals.onlinelibrary.wiley.com/doi/abs/10.1002/ohn.850

Outcomes of Immunotherapy in Sinonasal Mucosal Melanoma ... We report outcomes of immunotherapy in recurrent SNMM patients with distant versus nondistant recurrence. Fifty-four patients with recurrent ...

6. mdpi.com mdpi.com/2075-4426/14/12/1120

Survival Outcomes in Sinonasal Mucosal Melanoma They also reported a 5-year OS after adjuvant immunotherapy treatment of 42.6% (95% CI: 39.4–45.8), which is slightly higher than our global 5-year OS of 34.8 ( ...