Active not recruitingPHASE3INTERVENTIONAL

A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)

This research study, called SEACRAFT-2, is investigating a new treatment approach for advanced melanoma that has a specific genetic change called an 'NRAS mutation'. The study involves combining two medicines, naporafenib and trametinib, and comparing them to treatments doctors usually choose (dacarbazine, temozolomide, or trametinib alone). We want to find out if this new combination helps patients live longer without their cancer getting worse, and whether it helps them live longer overall. This study is for people whose melanoma has progressed after receiving other treatments like immunotherapy. It's a key step in understanding if these new medicines could offer a better option for future care.

At a glance

Status

Active not recruiting

Phase

PHASE3

Sponsor

Erasca, Inc.

Enrolment target

Start

29 Apr 2024

Estimated completion

01 Dec 2028

Advanced or Metastatic NRAS-mutant Melanoma

What is this study about?

This study is designed to find out if a new combination of medicines, called naporafenib and trametinib, can be a better treatment option for a specific type of advanced skin cancer called melanoma. This particular study is for people whose melanoma has a genetic change known as an 'NRAS mutation' and has continued to grow or spread even after they've had other treatments, specifically a type of immunotherapy. We know that these genetic changes can make melanoma harder to treat, so doctors are always looking for new ways to help.

The study is split into two main parts. In the first part, a small group of patients will help doctors figure out the best and safest dose of naporafenib to use when it's given with trametinib. This is important to make sure patients get enough medicine to be effective, but not so much that side effects become too difficult. Once the best dose is found, the study moves to the second, larger part.

In the second part, many more patients will take part. They will be randomly assigned to either receive the new combination of naporafenib and trametinib, or to receive one of the standard treatments that doctors often choose for this type of melanoma (which could be dacarbazine, temozolomide, or trametinib on its own). Doctors will then carefully compare how well these different treatments work, looking at things like whether the cancer shrinks or stops growing, and how long people are living. The main goal is to see if the new combination can help patients live longer and keep their cancer under control for a longer period.

Key takeaways

Tests a new combination of medicines (naporafenib + trametinib) for advanced melanoma.
Specifically for melanoma with an NRAS genetic change that has progressed after immunotherapy.
Compares the new combination to standard treatments chosen by your doctor.
Aims to see if the new treatment helps people live longer and keeps cancer under control.
This is a large, important study (Phase 3) that could lead to new treatment options.

Who may be eligible?

This study is looking for adults aged 18 or older who have melanoma that has spread or can't be removed with surgery, and which has a specific genetic change called an 'NRAS mutation'. It's important that your melanoma has started to grow again or spread after you've already had a type of immune-boosting treatment. You should also be generally well enough to take part in the study, meaning you can mostly look after yourself.

There are certain reasons why you might not be able to join. For example, if you have a different type of melanoma, like one in your eye or mouth, this study wouldn't be for you. If you've had similar types of targeted treatments before that block specific cancer pathways (like ERK-, MEK-, RAF-, or RAS-inhibitors), you wouldn't be eligible. Also, if you have certain heart problems, eye conditions, or serious stomach and bowel issues that might affect how you take the medicine, you wouldn't be able to participate. uncontrolled brain metastases would also exclude you from the study.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you 18 years old or older?
Do you have advanced melanoma that has spread or can't be removed?
Has your melanoma been tested and shown to have an 'NRAS mutation'?
Has your melanoma progressed after you've had a type of immune system-boosting treatment (like anti-PD-1/L1)?
Are you generally well and able to swallow pills?
Do you have any serious heart, eye, or stomach/bowel conditions, or have you recently had similar targeted treatments to this study?

Answer every question to see your result.

What does participation involve?

If you join this study, it will involve several visits to the clinic, which could include blood tests, physical examinations, and scans to check how your cancer is responding. The study medicine, naporafenib and trametinib, are taken by mouth as pills. You'll be given clear instructions on how and when to take them. If you are in the control group, you'll receive one of the standard treatments, which might be an infusion or pills, depending on the medicine chosen by your doctor.

The study will continue for as long as the treatment is working for you and you are tolerating it well. After you stop taking the study medicine, you'll have follow-up visits or calls to monitor your health. The exact length of follow-up will vary for each person.

Potential risks and benefits

Taking part in any clinical trial has potential benefits and risks. A potential benefit could be that the new combination treatment works better for your cancer than existing options, helping to control your disease for longer. However, there's no guarantee the treatment will work for you, and like all medicines, naporafenib and trametinib can cause side effects. These could range from mild to more serious, and the study team will monitor you closely for them. You will also be compared to standard treatments that are already available. It's very important to remember that you are free to leave the study at any time, for any reason, without it affecting your usual medical care.

Locations (59)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

Mayo Clinic - Arizona
Verified postcode
Phoenix, United States
University of California, San Francisco
Verified postcode
San Francisco, United States
The Melanoma and Skin Care Institute
Verified postcode
Englewood, United States
Mayo Clinic - Florida
Verified postcode
Jacksonville, United States
University of Miami Sylvester Cancer
Verified postcode
Miami, United States
University of Kansas Cancer Center
Verified postcode
Kansas City, United States
Ochsner Clinic Foundation
Verified postcode
Jefferson, United States
Massachusetts General Hospital
Verified postcode
Boston, United States
Barbara Ann Karmanos Cancer Institute
Verified postcode
Detroit, United States
Mayo Clinic
Verified postcode
Rochester, United States
Washington University School of Medicine
Verified postcode
St Louis, United States
Memorial Sloan Kettering Cancer Center
Verified postcode
New York, United States

Common questions

What is an NRAS-mutant melanoma?

It's a type of skin cancer where the cancer cells have a specific genetic change (mutation) in something called the NRAS gene. This change can affect how the cancer grows.

What do naporafenib and trametinib do?

These are targeted medicines designed to block specific signals within cancer cells that tell them to grow and divide, hopefully slowing down or stopping the cancer's progression.

What does 'Phase 3' mean for a study?

Phase 3 means this is a large study that compares the new treatment to standard care to see if it's better. If successful, it's often the last step before a medicine might be approved for wider use.

Will I know which treatment I'm getting?

Yes, this is an 'open-label' study, meaning both you and your doctor will know whether you are receiving the naporafenib and trametinib combination or one of the doctor's choice treatments.

What happens if the treatment stops working?

If the study treatment stops being effective or you cannot tolerate it, your study doctor will discuss other treatment options with you outside of the trial.