Not recruiting

Study on Retreatment with Encorafenib and Cetuximab for Patients with BRAF V600E Mutated Metastatic Colorectal Cancer

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 a type of cancer known as metastatic colorectal cancer, which is a form of cancer that starts in the colon or rectum and spreads to other parts of the body. The study is investigating the effectiveness of a treatment combination involving two medications: encorafenib and cetuximab. Encorafenib, also known by its code name LGX818, is a type of medication called a kinase inhibitor, which works by blocking certain proteins that help cancer cells grow. Cetuximab is a monoclonal antibody, a type of protein that can attach to cancer cells and help the immune system destroy them.

The purpose of this study is to evaluate how well this combination treatment works in patients who have a specific mutation in their cancer called BRAF V600E. This mutation is a change in the DNA of the cancer cells that can affect how the cancer grows. The study will involve patients who have previously been treated with these medications and are now being considered for retreatment. During the study, participants will receive the treatment and be monitored regularly to assess their response to the therapy. This will include regular imaging tests to check the size of the cancer and see if it is responding to the treatment.

The study will last for a period of time, during which participants will receive the treatment and have regular check-ups to monitor their health and the cancer's response. The goal is to understand how effective the treatment is in controlling the cancer and to gather information on any side effects experienced by the participants. This information will help doctors better understand the potential benefits and risks of using encorafenib and cetuximab for treating metastatic colorectal cancer with the BRAF V600E mutation.

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
Enrollment
Upon joining the study, a blood sample is required for ctDNA analysis. This must be done within 28 days before enrollment.
Eligibility is confirmed based on specific genetic markers in the ctDNA, including the presence of the BRAF V600E mutation and the absence of certain other mutations.
Step 2
Treatment initiation
The treatment involves two medications: Erbitux and Braftovi.
Erbitux is administered as an intravenous infusion. The dosage and frequency are determined by the healthcare provider.
Braftovi is taken orally in the form of hard capsules. The dosage and frequency are determined by the healthcare provider.
Step 3
Treatment monitoring
Regular monitoring is conducted to assess the response to treatment. This includes imaging tests such as CT scans every 8 weeks to evaluate the size of the cancer.
Blood tests and other assessments are performed to monitor overall health and any side effects from the treatment.
Step 4
Response evaluation
The effectiveness of the treatment is measured by the Objective Response Rate (ORR), which looks at the percentage of patients achieving a complete or partial response.
Progression-Free Survival (PFS) and Overall Survival (OS) are also evaluated to understand the duration of benefit from the treatment.
Step 5
Quality of life assessment
Quality of life is assessed using specific questionnaires designed to evaluate the impact of the treatment on daily living.
These assessments help understand the balance between treatment benefits and any side effects experienced.
Step 6
Study completion
The study is expected to continue until March 2026, with regular assessments throughout the duration.
Upon completion, final evaluations are conducted to determine the overall outcomes of the treatment.

Who can join the trial?

26 criteria

Confirmed diagnosis of colorectal adenocarcinoma, which is a type of cancer that starts in the colon or rectum.
Previously treated with immune checkpoint inhibitors, which are drugs that help the immune system fight cancer, if the cancer is MSI-H or dMMR mCRC.
Blood sample available for ctDNA analysis within 28 days before joining the study. ctDNA is a type of DNA found in the blood that comes from cancer cells.
BRAFV600E mutation present in ctDNA at screening. This is a specific change in the DNA that can affect cancer growth.
No mutations in KRAS, NRAS, MAP2K1 genes, and no MET gene amplification in ctDNA at screening. These are specific genetic conditions that need to be checked.
Archival tumor tissue available for biomarker analysis. This means having a sample of the tumor stored for further testing.
Neutrophils (a type of white blood cell) greater than 1.5 x 10⁹/L, platelets (cells that help with blood clotting) greater than 100 x 10⁹/L, and hemoglobin (Hgb, a protein in red blood cells) greater than 9 g/dL. Blood transfusions are allowed if not more than two units of red blood cells were received in the last 4 weeks to meet this requirement.
Good kidney function, shown by a serum creatinine level (a waste product in the blood) less than or equal to 1.5 times the upper limit of normal, or a creatinine clearance (a measure of kidney function) of at least 50 mL/min at screening.
Good liver function, shown by specific levels of bilirubin (a substance made by the liver) and liver enzymes (ALT and AST) at screening. Special conditions apply for patients with Gilbert's syndrome, a mild liver disorder.
Normal levels of electrolytes, such as potassium and magnesium, at the start of the study. Treatment to correct these levels is allowed if needed.
INR or aPTT (tests that measure blood clotting) less than or equal to 1.5 times the upper limit of normal.
Age 18 years or older.
QT interval (a measure of heart rhythm) corrected for heart rate less than or equal to 480 milliseconds at screening.
Able to take medications by mouth.
Women who can have children must have a negative blood pregnancy test at screening. This includes all women after puberty unless they meet specific conditions like being postmenopausal or surgically sterile.
Participants and their partners must agree to avoid pregnancy from the start of the study until 1 month after the last treatment. This includes using effective birth control methods.
Written informed consent to participate in the study procedures.
Expected to live at least twelve weeks.
Willing and able to follow the study protocol.
ECOG Performance status of 0 or 1, which is a scale used to assess how a patient's disease is affecting their daily living abilities.
BRAFV600E mutation confirmed in the primary colorectal cancer or related metastasis by local laboratory testing.
Metastatic disease with at least one measurable lesion according to RECIST 1.1 criteria, which are guidelines for measuring cancer response to treatment.
Previously treated with encorafenib plus cetuximab, with or without chemotherapy, showing a complete or partial response or stable disease for at least 6 months.
Documented disease progression according to RECIST 1.1 during or after previous treatment with encorafenib plus cetuximab, with or without chemotherapy.
At least one other treatment line, not including BRAF and EGFR inhibitors, between the end of the first treatment with encorafenib plus cetuximab and the time of screening.
At least 4 months have passed since the end of the previous treatment with encorafenib plus cetuximab before starting retreatment.

Who cannot join the trial?

7 criteria

Patients who do not have **metastatic colorectal cancer**. This means the cancer has spread from the colon or rectum to other parts of the body.
Patients who do not have the **BRAFV600E mutation**. This is a specific change in the BRAF gene that can affect cancer growth.
Patients who have mutations in the **KRAS, NRAS, or MAP2K1 genes**. These are other genes that, if changed, can affect cancer treatment.
Patients who have an **amplified MET status**. This means there are extra copies of the MET gene, which can influence cancer behavior.
Patients who are not experiencing benefit from previous treatment with **BRAF and EGFR blockade**. This refers to specific types of cancer treatments that target certain proteins involved in cancer growth.
Patients who are not within the specified **age range** for the study. The study is open to certain age groups only.
Patients who are not willing or able to follow the study procedures and requirements.

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Verified sites

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

Azienda Ospedaliera Universitaria Citta' Della Salute E Della Scienza Di Torino
Verified
Turin, Italy
Azienda Ospedaliero Universitaria Careggi
Responsive
Florence, Italy
Istituto Oncologico Veneto
Responsive
Padua, Italy

Trial locations

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Investigated drugs

Encorafenib
is a medication used in this study to target specific cancer cells with a mutation known as BRAF V600E. It works by blocking certain proteins that help cancer cells grow, which may slow down or stop the growth of the cancer.
Cetuximab
is another medication used in the study. It is a type of therapy that targets a protein on the surface of cancer cells called EGFR. By blocking this protein, cetuximab can help stop the cancer cells from growing and dividing.

What is already known about the treatment

Encorafenib
Encorafenib is administered orally in the form of tablets. It is currently being studied in clinical trials for its effectiveness in treating metastatic colorectal cancer, particularly in patients with a specific BRAF V600E mutation. The medication works by inhibiting the BRAF protein, which is involved in cell growth and division, thereby slowing down the growth of cancer cells. It is classified as a BRAF inhibitor, a type of targeted cancer therapy.
Cetuximab
Cetuximab is administered intravenously, typically through an infusion. It is an established treatment in the medical field for certain types of cancer, including metastatic colorectal cancer. Cetuximab targets the epidermal growth factor receptor (EGFR) on the surface of cancer cells, blocking signals that promote tumor growth. It is classified as a monoclonal antibody, which is a type of targeted therapy used to treat cancer.

Investigated diseases

Metastatic Colorectal Cancer – This is a type of cancer that originates in the colon or rectum and has spread to other parts of the body, such as the liver or lungs. It typically begins as a growth, called a polyp, on the inner lining of the colon or rectum, which can become cancerous over time. As the disease progresses, cancer cells can break away from the original tumor and travel through the bloodstream or lymphatic system to form new tumors in distant organs. The progression of metastatic colorectal cancer can vary, with some patients experiencing rapid spread, while others may have a slower progression. Symptoms may include changes in bowel habits, blood in the stool, abdominal pain, and unexplained weight loss. The disease is often diagnosed at an advanced stage due to the subtlety of early symptoms.