Recruiting

Study of ipilimumab and nivolumab injected into tumors before surgery in patients with stage III melanoma that can be removed by surgery

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What is this trial about?

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

This study looks at localized solid malignancies that can be treated before surgery and at resectable stage III cutaneous or mucosal melanoma. Melanoma is a type of skin cancer that can also occur on mucous membranes. Stage III means the cancer has spread to nearby lymph nodes but not to distant parts of the body. Resectable means the tumor can be removed by surgery. The treatment being tested involves two medicines called nivolumab (also known by the code name BMS936558) and ipilimumab. Both medicines are given directly into the tumor before surgery, which is called intratumoral administration. These medicines work by helping the body's immune system recognize and fight cancer cells. The purpose of the study is to evaluate how well this treatment combination works and how safe it is when given before surgery in patients with melanoma.

The study involves giving the two medicines directly into the tumor over a period of up to six weeks before the planned surgery. During this time, patients will receive nivolumab at a dose of up to 30 milligrams per day with a total of up to 90 milligrams, and ipilimumab at a dose of up to 25 milligrams per day with a total of up to 75 milligrams. After completing the treatment, patients will undergo surgery to remove the tumor. The doctors will then examine the removed tissue to see how much of the cancer was destroyed by the treatment. The study will measure whether the cancer was completely eliminated or whether there was a major response with less than 10 percent of cancer cells remaining.

Throughout the study, doctors will monitor patients for any side effects and will check whether the treatment causes any delays in the planned surgery date. After surgery, patients will be followed to see how long they remain free of cancer and to track their overall health and survival. The study will also assess quality of life using questionnaires at different time points during and after treatment. Safety will be monitored by tracking all side effects according to standard cancer treatment safety guidelines. The study will continue to follow patients for several years after surgery to see if the cancer returns and to measure long-term outcomes.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Baseline evaluation and screening
Before starting treatment, a baseline evaluation will be performed. This includes blood tests and tissue samples (biopsies) from the tumor to analyze its characteristics.
A pregnancy test will be performed if applicable, which must be negative within 7 days before treatment begins.
Blood tests will check organ function, including liver function (bilirubin and ALT, which measure liver health), kidney function (creatinine clearance, which measures how well the kidneys filter waste), blood cell counts (neutrophils, platelets, hemoglobin), and albumin levels (a protein in the blood).
The tumor will be measured according to standardized criteria called RECIST v1.1, which is a method to assess tumor size and response to treatment.
A quality of life questionnaire called EORTC QLQ-C30 will be completed to assess overall well-being and symptoms.
Step 2
Treatment period with study medications
Treatment will be administered with two medications: nivolumab (also known as Opdivo) and ipilimumab (also known as Yervoy).
Both medications will be given directly into the tumor, which is called intratumoral administration.
Nivolumab is provided as a concentrated liquid at 10 mg per milliliter, prepared for infusion.
Ipilimumab is provided as a concentrated liquid at 5 mg per milliliter, prepared for infusion.
These medications are types of immunotherapy, which work by helping the immune system recognize and attack cancer cells. Specifically, they block proteins called CTLA-4 and PD-1 that prevent the immune system from fighting the cancer.
During each treatment cycle, the quality of life questionnaire will be completed to monitor symptoms and well-being.
Regular monitoring for side effects will be performed throughout the treatment period. Any adverse events will be classified using the NCI-CTCAE v5.0 system, which is a standard method for grading the severity of side effects.
Tumor response will be assessed using RECIST v1.1 criteria to determine if the tumor is shrinking, staying stable, or growing.
Step 3
Evaluation at 6 weeks
At 6 weeks, an evaluation will be performed to assess the tumor response to treatment.
This assessment will determine if there is complete response (tumor has completely disappeared), partial response (tumor has shrunk significantly), or stable disease (tumor has not grown or shrunk significantly).
Step 4
Surgery
Surgery will be performed to remove the tumor according to the planned timeline.
The surgery should not be delayed by more than 4 weeks beyond the planned date due to treatment-related side effects.
During surgery, the tumor tissue will be removed and examined in detail.
The tissue will be analyzed to determine the pathological response, which means how much of the tumor has been destroyed by the treatment.
A pathological complete response (pCR) means no living tumor cells remain in the removed tissue.
A major pathologic response (MPR) means less than 10% of the tumor cells are still alive in the removed tissue.
A quality of life questionnaire will be completed at the time of surgery.
Step 5
Follow-up period - first year
After surgery, regular follow-up visits will be scheduled to monitor recovery and check for any signs of cancer returning.
Quality of life questionnaires will be completed at specific time points: 1 month, 3 months, 6 months, and 12 months after surgery.
During follow-up, assessments will monitor for cancer recurrence, which means the cancer coming back.
Assessments will also check for distant metastases, which means cancer spreading to other parts of the body.
The time from surgery until any evidence of cancer returning or death from any cause will be recorded as recurrence-free survival.
The time from enrollment until evidence of cancer spreading to distant sites or death from any cause will be recorded as distant metastasis-free survival.
Step 6
Long-term follow-up
Long-term follow-up will continue beyond the first year to monitor overall health and survival.
Overall survival will be tracked, which is the time from enrollment in the study until death from any cause.
If contraception was used during the study, it should be continued for the period specified after the last dose of study medication.

Who can join the trial?

18 criteria

You must be at least 18 years old
You must have stage III melanoma (a type of skin cancer) that can be removed by surgery and can be measured
The melanoma must be cutaneous (on the skin) or mucosal (on mucous membranes like inside the mouth or nose)
If you previously received anti-PD-1 treatment (a type of immunotherapy that helps your immune system fight cancer), you must have stopped it more than 6 months before joining this study
If you previously received target therapy (a type of cancer treatment that targets specific molecules), you must have stopped it more than 3 months before joining this study
You must be affiliated with the French social security system
You must be mentally and legally able to give your full consent for the procedures in the study, including blood draws and biopsies (removing small tissue samples for testing)
You must be willing and able to follow the study plan, including attending all scheduled visits and examinations
You must have signed a written consent form before joining the study
You must have at least one tumor that can be measured according to specific measurement guidelines
Your ECOG performance status (a scale that measures how well you can perform daily activities) must be between 0 and 2, meaning you are able to care for yourself
You must be able to undergo blood draws and tumor biopsy procedures
Your liver must be working adequately: total bilirubin (a substance made by the liver) must be no more than 1.5 times the upper normal limit, and ALT (a liver enzyme) must be no more than 3 times the upper normal limit
Your blood counts must be adequate: absolute neutrophils (a type of white blood cell) at least 1000 cells per cubic millimeter, platelets (cells that help blood clot) at least 100,000 per cubic millimeter, and hemoglobin (the protein in red blood cells that carries oxygen) at least 9.0 grams per deciliter
Your albumin (a protein in blood) level must be at least 30 grams per liter
Your kidney function must be adequate: creatinine clearance (a measure of how well your kidneys filter waste) must be at least 50 milliliters per minute
If you are a woman who can become pregnant, you must have a negative pregnancy test within 7 days before starting treatment
If you are sexually active and able to become pregnant, or if you are a male partner of someone who can become pregnant, you must agree to use two effective methods of contraception (birth control), including one barrier method, or abstain from sexual activity during the study and for a specified period after the last dose of study medication

Who cannot join the trial?

2 criteria

The specific exclusion criteria (reasons why you cannot participate) have not been provided in the available study information. Your doctor will need to review the complete study requirements to determine if you are eligible to participate.
Generally, clinical trials may exclude patients based on factors such as other medical conditions, previous treatments, laboratory test results, or medications you are currently taking, but these specific details are not available in this document.

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Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

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Assistance Publique Hopitaux De Marseille
Marseille, France
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Centre Hospitalier Lyon Sud
Pierre Benite, France
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Centre Hospitalier Universitaire De Bordeaux
Bordeaux, France

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Investigated drugs

Ipilimumab
is a type of cancer medicine that helps your immune system fight cancer cells. It works by blocking a protein called CTLA-4, which allows your immune system to recognize and attack cancer cells more effectively. In this trial, it will be injected directly into the tumor before surgery.
Nivolumab
is another type of cancer medicine that helps your immune system fight cancer. It works by blocking a protein called PD-1, which helps your immune cells become more active against cancer. In this trial, it will be injected directly into the tumor along with ipilimumab before surgery to help treat melanoma.

What is already known about the treatment

Ipilimumab
Ipilimumab is a medication given by injection directly into tumors or through an intravenous infusion, and it is an established cancer treatment approved for use in melanoma and other cancers. It works by blocking a protein called CTLA-4 on immune cells, which removes the brakes from the immune system and allows it to recognize and attack cancer cells more effectively. This medication belongs to a class of drugs called immune checkpoint inhibitors, which help the body's natural defense system fight cancer. In this clinical trial, it is being studied in combination with another immunotherapy drug as a treatment given before surgery for patients with stage III melanoma.
Nivolumab
Nivolumab is an injectable cancer medication that is currently approved and widely used for treating various types of cancer, including melanoma, lung cancer, and kidney cancer. It works by blocking a protein called PD-1 on immune cells, which prevents cancer cells from hiding from the immune system and enables the body to mount a stronger attack against the tumor. This drug is classified as an immune checkpoint inhibitor, a type of immunotherapy that enhances the natural ability of the immune system to fight cancer. In this study, it is being tested in combination with ipilimumab and injected directly into tumors before surgical removal in patients with localized melanoma.

Investigated diseases

Cutaneous Melanoma
Cutaneous melanoma is a type of skin cancer that develops from pigment-producing cells called melanocytes. It typically begins as an abnormal growth or change in an existing mole on the skin. The disease can progress through different stages, with stage III indicating that the cancer has spread to nearby lymph nodes or skin areas close to the original tumor. In its resectable stage III form, the tumor can still be removed through surgery. Without intervention, the cancer may continue to spread to distant parts of the body. The progression involves the uncontrolled growth and multiplication of abnormal melanocytes.
Mucosal Melanoma
Mucosal melanoma is a rare form of melanoma that develops in the mucous membranes lining various body cavities and passages. These membranes can be found in areas such as the nasal passages, mouth, throat, digestive tract, and genital areas. The disease occurs when pigment-producing cells in these moist tissue linings begin to grow abnormally. Stage III mucosal melanoma means the cancer has grown locally and may have spread to nearby lymph nodes. This type of melanoma tends to be detected later than skin melanoma because it develops in less visible locations. The disease progresses as abnormal cells multiply and invade surrounding tissues.