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Study Comparing Ipilimumab and Nivolumab with Standard Nivolumab for Patients with Stage III Melanoma

Verified siteRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying treatments for Stage III melanoma, a type of skin cancer that has spread to nearby lymph nodes. The study is comparing two different treatment approaches. One group of patients will receive a combination of two medications, Ipilimumab and Nivolumab, before surgery. This is known as neoadjuvant therapy, which means treatment given as a first step to shrink a tumor before the main treatment, usually surgery. After surgery, these patients may continue with Nivolumab or switch to other medications if needed. The other group will receive Nivolumab after surgery, which is called adjuvant therapy, meaning treatment given after the primary treatment to lower the risk of the cancer coming back.

The purpose of the study is to compare how well these treatments work in preventing the cancer from returning or spreading. The trial will involve regular visits to the clinic for treatment, which is given through an intravenous infusion, meaning the medication is delivered directly into a vein. Patients will be monitored over a period of time to see how the cancer responds to the treatment and to check for any side effects. Some patients may receive a placebo, which is a substance with no active medication, to help compare the effects of the actual treatments.

Throughout the study, doctors will assess the health and progress of the participants, looking at factors like the time it takes for the cancer to progress or return, and overall survival rates. The study aims to provide valuable information on the effectiveness of these treatment strategies for Stage III melanoma, potentially leading to improved outcomes for patients with this condition.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial treatment phase

    The trial begins with the administration of two medications: ipilimumab and nivolumab. These are given as a solution through an intravenous infusion.

    The purpose of this phase is to prepare the body for the main treatment by using these medications to help the immune system recognize and attack cancer cells.

  2. Step 2

    Neoadjuvant treatment

    During this phase, the combination of ipilimumab and nivolumab is administered. This is done to shrink the tumor before surgery.

    The treatment is given through an intravenous infusion, which means the medication is delivered directly into the bloodstream.

  3. Step 3

    Surgery

    After the neoadjuvant treatment, surgery is performed to remove the tumor and any affected lymph nodes.

    The goal of the surgery is to eliminate as much of the cancer as possible.

  4. Step 4

    Adjuvant treatment

    Following surgery, nivolumab is administered as an adjuvant treatment. This is intended to prevent the cancer from returning.

    In some cases, if the initial treatment did not achieve the desired response, a combination of dabrafenib and trametinib may be used instead.

  5. Step 5

    Follow-up and monitoring

    Regular follow-up visits are scheduled to monitor the patient's health and check for any signs of cancer recurrence.

    These visits may include physical exams, imaging tests, and blood tests to ensure the treatment is working effectively.

Who can join the trial?

13 criteria

  • Men and women, at least 16 years of age.
  • Women who can have children must use a reliable method of birth control to prevent pregnancy during the study and for 23 weeks after the last dose of the study drugs ipilimumab and nivolumab.
  • Men who are sexually active with women who can have children do not need to use birth control during treatment with nivolumab and/or ipilimumab, but must use a reliable method of birth control to prevent pregnancy during the study and for 17 weeks after the last dose of the study drugs dabrafenib and trametinib.
  • Patient must be willing and able to understand the study requirements and follow the treatment schedule, attend scheduled visits, report outcomes electronically, undergo tumor biopsies and extra blood tests during screening and if the cancer returns, and meet other study requirements.
  • Patient must have signed the Informed Consent document, which means they agree to participate in the study after being informed about it.
  • Patient must have a **World Health Organization (WHO) Performance Status** of 0 or 1, which means they are fully active or have some symptoms but do not need help with daily activities.
  • Patient must have a confirmed diagnosis of **resectable stage III melanoma**, which is a type of skin cancer that can be surgically removed, with one or more large lymph node metastases that can be detected and biopsied. A maximum of 3 additional resectable in-transit metastases is allowed. A concurrent resectable primary melanoma is also allowed.
  • Patient must not have any other cancers, except those that have been treated and have a life expectancy of more than 5 years related to cancer.
  • Patient must not have had any previous **immunotherapy** targeting specific proteins like CTLA-4, PD-1, PD-L1, or LAG-3, which are used to help the immune system fight cancer.
  • Patient must not have had any previous **targeted therapy** targeting BRAF and/or MEK, which are specific treatments for certain types of cancer.
  • Patient must not have taken any **immunosuppressive medications** within 6 months before joining the study, except for low-dose steroids equivalent to prednisolone 10 mg or less.
  • Patient's laboratory test results must meet specific criteria, including certain levels of white blood cells, neutrophils, platelets, hemoglobin, creatinine, AST, ALT, and bilirubin. These tests help ensure the patient is healthy enough to participate in the study.
  • Patient's **LDH level** must be less than 1.5 times the upper limit of normal. LDH is a substance in the blood that can be higher in some medical conditions.

Who cannot join the trial?

6 criteria

  • Patients with any other type of cancer besides Stage III melanoma cannot participate. Melanoma is a type of skin cancer, and Stage III means it has spread to nearby lymph nodes.
  • Patients who are not within the specified age range for the study cannot participate. The age range is typically defined by the study and may include specific age groups.
  • Patients who are part of a vulnerable population, such as those who cannot give consent or have certain health conditions, are not eligible.
  • Patients who are not able to follow the study procedures or attend required visits may be excluded.
  • Patients who have received certain treatments or medications that could interfere with the study may not be eligible.
  • Patients with certain medical conditions that could affect the study results or their safety may be excluded.
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Investigated drugs

  • Ipilimumab

    is a medication used to help the immune system attack cancer cells. It works by blocking a specific protein that usually stops the immune system from working strongly. In this trial, it is used before surgery to try to shrink the melanoma tumors.

  • Nivolumab

    is another medication that helps the immune system fight cancer. It also blocks a protein that can slow down the immune system, allowing it to attack cancer cells more effectively. In this trial, it is used both before and after surgery to treat melanoma.

  • Dabrafenib

    is a medication that targets specific proteins in cancer cells, which helps to stop the cancer from growing. It is used in this trial for patients who do not respond to the initial treatment, to help control the melanoma.

  • Trametinib

    is a medication that works by blocking certain proteins that are involved in the growth and spread of cancer cells. It is used in combination with dabrafenib in this trial for patients who need additional treatment after the initial therapy.

What is already known about the treatment

  • Ipilimumab

    This medication is administered intravenously and is currently being studied in clinical trials for its effectiveness in treating stage III melanoma. It is used in combination with nivolumab as a neoadjuvant therapy, meaning it is given before the main treatment to shrink tumors. Ipilimumab works by activating the immune system to attack cancer cells, specifically by blocking a protein called CTLA-4, which normally helps keep immune responses in check. It is classified as an immune checkpoint inhibitor.

  • Nivolumab

    Administered intravenously, nivolumab is an established medication in the treatment of various cancers, including stage III melanoma. It is used both as a neoadjuvant and adjuvant therapy, meaning it can be given before or after the main treatment. Nivolumab enhances the immune system's ability to fight cancer by blocking the PD-1 protein on immune cells, preventing cancer cells from evading immune detection. It is also classified as an immune checkpoint inhibitor.

  • Dabrafenib

    This medication is taken orally and is used in the treatment of melanoma with a specific genetic mutation known as BRAF V600. It is often combined with trametinib to improve effectiveness. Dabrafenib works by inhibiting the activity of the BRAF protein, which is involved in cell growth, thereby slowing or stopping the growth of cancer cells. It is classified as a BRAF inhibitor.

  • Trametinib

    Administered orally, trametinib is used in combination with dabrafenib for treating melanoma with the BRAF V600 mutation. It works by inhibiting the MEK proteins, which are part of a pathway that promotes cell division and growth. By blocking this pathway, trametinib helps to slow down or stop the growth of cancer cells. It is classified as a MEK inhibitor.

Investigated diseases

Stage III Melanoma – This is a type of skin cancer that has spread to nearby lymph nodes but not to distant parts of the body. It often begins as a mole or pigmented area on the skin that changes in size, shape, or color. As it progresses, the cancer cells invade deeper layers of the skin and nearby tissues. The disease can cause symptoms such as swelling of lymph nodes, changes in skin appearance, and sometimes ulceration. Stage III melanoma is categorized based on the extent of lymph node involvement and the presence of microscopic or macroscopic metastases. The progression of the disease can vary, with some cases remaining stable for a period while others may advance more rapidly.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2024-513519-28-00Protocol codeM23MAREstimated enrolment423 patientsSponsorHet Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

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