Pre-surgery Immunotherapy for Melanoma

Not currently recruiting at 3 trial locations

Overseen By Michael Postow, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants

Disqualifiers: Autoimmune disease, Hepatitis B, HIV/AIDS, others

Stay on Your Current Meds You can continue your current medications while participating

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of two immunotherapy drugs, nivolumab and ipilimumab, given before surgery, can help the immune system shrink melanoma tumors and prevent their return post-surgery. Researchers are also using a new type of PET scan to assess the immune system's response to this treatment. Individuals with surgically removable melanoma and visible tumors on standard imaging may be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant advancements in melanoma treatment.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have active autoimmune disease requiring immunosuppression or if you are using other investigational drugs within 30 days before the study.

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

The trial information does not specify whether you need to stop taking your current medications. However, if you are on investigational drugs, you must stop them at least 30 days before starting the study treatment.

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

Research has shown that the combination of nivolumab and ipilimumab has been tested for safety in people with melanoma. These drugs are a type of immunotherapy, which helps the immune system fight cancer.

In earlier studies, some patients who took nivolumab and ipilimumab together experienced side effects. For instance, about 2.5% of patients had reactions when the drugs were administered through an IV. Specifically, out of 407 people, around 10 experienced these reactions.

Both drugs have FDA approval for treating melanoma, but side effects can vary. Common ones include fatigue, rash, and diarrhea. These side effects are usually manageable, but discussing any concerns with a doctor is important.

Understanding these details can help determine if joining a trial is right for you. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard approach for treating Stage III melanoma, which often involves surgery followed by post-surgical therapies like chemotherapy or radiation, this treatment plan introduces immunotherapy before surgery. Researchers are excited about this approach because pre-surgery immunotherapy can potentially shrink tumors, making them easier to remove and reducing the risk of recurrence. Additionally, this method may help prime the immune system to better recognize and fight any remaining cancer cells after surgery, offering a more comprehensive defense against the disease.

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

Research has shown that using the drugs nivolumab and ipilimumab before surgery can effectively treat stage III melanoma. In this trial, participants will receive this combination as neoadjuvant therapy to help the immune system attack and shrink the cancer before surgery. This method can reduce the spread of melanoma and improve patient outcomes. Specifically, past patients demonstrated better responses, meaning the cancer was less likely to return after surgery. Overall, these findings suggest that this treatment combination holds promise for people with melanoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael A. Postow

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain stages of melanoma (IIIB, IIIC, IIID, or IV) that can be removed by surgery. Participants must understand the study and agree to its rules. They should have good physical function and not be pregnant or nursing. People who've had specific immunotherapies or suffer from autoimmune diseases, severe allergies to antibodies, HIV/AIDS, hepatitis B infection, or other conditions making treatment risky are excluded.

Inclusion Criteria

I am fully active or can carry out light work.

My cancer's BRAF status does not affect my eligibility.

I understand the study requirements and have signed the consent form.

Exclusion Criteria

I do not have an active autoimmune disease or need for immunosuppression.

I have received immunotherapy targeting CTLA-4 or PD-1/PD-L1 before.

I have an active hepatitis B infection confirmed by a test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive combination treatment with nivolumab and ipilimumab before surgery to target and destroy melanoma tumors

6-8 weeks

Surgery

Participants undergo surgery to remove melanoma tumors

Follow-up

Participants are monitored for safety and effectiveness after surgery and treatment, including assessment of pathologic response

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• PET Scan
• Surgical Resection of Melanoma

Trial Overview The trial tests if combining nivolumab and ipilimumab as pre-surgery (neoadjuvant) therapy helps shrink melanoma tumors and prevent their return post-surgery. It also examines a new PET scan technique to see how well the immune system responds to this treatment.

How Is the Trial Designed?

Group I: Participants with Stage III Melanoma Experimental Treatment 4 Interventions

All participants will have cytologically or histologically confirmed stage IIIB, IIIC, IIID melanoma that can be surgically removed.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a study of 111 melanoma patients treated with immunotherapy or targeted therapy, the majority received immunotherapy, particularly anti-PD-1 treatments, with a total of 371 adverse events (AEs) reported.

The incidence of AEs was lower in patients receiving anti-PD-1 therapy, with only 15.3% experiencing severe (grade 3 to 4) AEs, which were more common in those on targeted therapies, highlighting the need for better reporting and understanding of both known and unknown AEs in cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma. Aguiar, JP., Cardoso Borges, F., Murteira, R., et al.[2021]

Surgical resection is often curative for early cutaneous melanoma, but some patients may experience relapse due to high-risk features in their tumors or lymph nodes.

Immunotherapy using checkpoint inhibitors like ipilimumab, nivolumab, and pembrolizumab has been shown to improve recurrence-free survival in patients with node-positive melanoma after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant immunotherapy for melanoma. Thomas, D., Bello, DM.[2021]

In a study of 14,433 patients with stage IV melanoma, it was found that the introduction of immunotherapy, particularly checkpoint inhibitors, did not significantly change the rates of surgical resection for metastatic disease compared to the period before these treatments were available.

The analysis revealed that patients receiving immunotherapy were generally younger, healthier, and had better socioeconomic status, indicating disparities in access to treatment among different patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of immunotherapy and surgery for stage IV melanoma. Molina, G., Kasumova, GG., Qadan, M., et al.[2021]

A systematic review of 18 studies on neoadjuvant immune checkpoint inhibitors (ICIs) for early-stage non-small-cell lung cancer (NSCLC) suggests that these treatments are generally safe and well tolerated, with low 30-day mortality rates (0% to 5.4%) and no significant adverse events reported as the main cause for surgery cancellations.

Surgery cancellation rates varied widely (0% to 45.8%), primarily due to disease progression rather than treatment-related adverse events, indicating that while ICIs are promising, careful monitoring of disease status is crucial before surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Neoadjuvant Immune Checkpoint Inhibitors on Surgery and Perioperative Complications in Patients With Non-small-cell Lung Cancer: A Systematic Review. Takada, K., Takamori, S., Brunetti, L., et al.[2023]

Neoadjuvant immune checkpoint inhibitors (ICIs) have shown improved outcomes in melanoma treatment, with 70-80% of patients experiencing recurrence-free survival at 2 years, based on a review of 61 phase II and III trials.

Biomarkers such as higher PD-L1 expression and CD8+ cell density can predict patient responses to ICIs, indicating that these treatments may significantly alter the standard approach for advanced resectable melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative Therapy in Melanoma: Evolving Perspectives in Clinical Trials. Kakish, H., Xu, K., Ahmed, FA., et al.[2023]

The combination of ipilimumab and nivolumab, when given before surgery, significantly enhances the immune response against advanced melanoma, leading to a high rate of complete tumor response.

In a reported case, this pre-surgical treatment increased the presence of CD8+ T cells in the tumor area, suggesting a stronger anti-tumor immune activity, making it a promising approach for patients with unresectable advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Unresectable Advanced Melanoma by Administration of Nivolumab With Ipilimumab Before Primary Tumor Resection. Fujimura, T., Kambayashi, Y., Sato, Y., et al.[2020]

Recent advancements in melanoma surgery have shifted from highly radical procedures with many complications to less invasive operations, improving patient outcomes.

The introduction of new systemic treatments, including targeted therapies and immunotherapy, has redefined the role of surgery in melanoma treatment, particularly reducing the need for extensive surgeries like elective block dissections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surgery for malignant melanoma - Expected standards]. Kádár, Z., Lengyel, Z., Gyulai, R.[2023]

Neoadjuvant systemic therapy using immune checkpoint inhibitors shows promise in improving recurrence-free survival for patients with stage III and IV melanoma, potentially outperforming the traditional approach of surgery followed by adjuvant therapy.

Early phase trials indicate that neoadjuvant therapy can lead to pathological complete response rates between 30% and 70%, suggesting it may be an effective strategy, although further studies are needed to determine optimal dosing and timing relative to surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Immune Checkpoint Inhibitor Therapy in Melanoma: Efficacy, Safety and Timing. van Akkooi, ACJ., Zijlker, LP., Wouters, MWJM.[2022]

Immunotherapy has significantly changed how melanoma is treated, influencing surgical decisions for both resectable and unresectable cases, which may lead to increased surgical interventions for metastatic melanoma.

While immunotherapies show great promise in controlling melanoma, further research is necessary to enhance their effectiveness while reducing potential side effects for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Immunotherapy Practices in Melanoma. Rothermel, LD., Sarnaik, AA., Khushalani, NI., et al.[2020]

A study of 236 patients receiving preoperative immunotherapy for non-small cell lung cancer showed that it is safe, with no significant differences in short-term outcomes like margin positivity, 30-day readmission, or mortality compared to 10,715 patients receiving preoperative chemotherapy.

Overall survival rates were similar between the immunotherapy group (63% at 5 years) and the chemotherapy group (51% at 5 years), indicating that immunotherapy is a feasible option before surgery without compromising patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Outcomes and Survival After Preoperative Immunotherapy for Non-Small Cell Lung Cancer. Mayne, NR., Potter, AL., Bharol, K., et al.[2022]

Surgery is the primary treatment for patients with localized melanoma (stages 0-II), involving wide excision and sentinel lymph node biopsy when necessary.

For stage III melanoma, surgery is preferred for patients with limited metastases, but the use of effective preoperative drugs should be considered, while stage IV melanoma management should involve a multidisciplinary team for optimal decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical management of melanoma. Sondak, VK., Gibney, GT.[2014]

Ipilimumab, a treatment for metastatic melanoma, can cause adverse events (AEs) in up to 64% of patients, including rare and potentially life-threatening conditions like DRESS and aseptic meningitis, highlighting the need for careful monitoring and management of side effects.

Despite the occurrence of severe AEs, ipilimumab showed a high response rate in patients, with 30.9% experiencing tumor regression and a 61.8% tumor control rate, suggesting that effective antitumor responses can occur even with limited treatment exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. Voskens, CJ., Goldinger, SM., Loquai, C., et al.[2022]

In a study of 9800 patients with stage IV melanoma, only 22% underwent surgery, and those who did were generally younger, had private insurance, and were treated at academic centers, indicating that access to surgery may be influenced by socioeconomic factors.

Patients receiving both surgery and immunotherapy had significantly better overall survival rates compared to those who received neither treatment, highlighting the potential benefits of combining these approaches in managing advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical Utilization and Outcomes for Patients with Stage IV Melanoma in the Modern Immunotherapy Era. Lwin, TM., Kaelberer, Z., Ruan, M., et al.[2023]

A study of 17 patients undergoing various surgeries while receiving immune checkpoint inhibitors (ICI) showed no severe complications (Grade III-IV) in the 30 days post-surgery, suggesting that ICI are safe in the perioperative setting.

The findings indicate that ICI, including pembrolizumab and ipilimumab, do not need to be discontinued during surgery, although further research is needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Feasibility and Safety of Surgery in Patients Receiving Immune Checkpoint Inhibitors: A Retrospective Study. Elias, AW., Kasi, PM., Stauffer, JA., et al.[2022]

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Neoadjuvant Immunotherapy in Melanoma: The Paradigm ... In this chapter, we will discuss the rationale for neoadjuvant immunotherapy; review impactful clinical trials; and define response monitoring, surgical ...