This trial aims to test the safety and effectiveness of combined treatment with dabrafenib (Tafinlar) and trametinib (Mekinist) in patients with inoperable advanced BRAF mutated melanoma. The main outcome to be measured will be the time to disease progression, response rates, and the number of negative side effects.
The details
Some melanoma patients have a mutation (permanent change) in the BRAF gene. BRAF inhibitors (such as dabrafenib) are used to treat these tumors. Over time, patients can become resistant to this treatment. This resistance happens due to the reactivation of a certain protein (MAPK) that allows for tumor growth. Adding an MAPK inhibitor to the treatment (such as trametinib) could help to overcome BRAF resistance.
A combination of these two therapies could significantly benefit the patient. However, it is not clear whether they are safe and effective when used in combination.
The current trial will examine combination treatment with dabrafenib and trametinib in patients with advanced melanoma. The main outcome will be measured through tumor response to the treatment and the frequency of side effects.
Who are they looking for?
This trial will recruit 280 participants with stage 3 or 4 BRAF mutated inoperable melanoma. Patients must not have received a prior BRAF inhibitor treatment and must not have brain metastasis Patients must have normal blood values.
Patients must not have any other serious medical condition, such as immune system diseases, cardiac disease, pulmonary disease, retinal (eye) disease, HIV or hepatitis. Patients must not have impaired gastrointestinal function. Female patients must not be pregnant or breastfeeding.
How will it work
Patients will be randomly divided into two groups. One group will receive dabrafenib orally twice a day and trametinib orally once daily on days 1-56. The other group will receive dabrafenib orally twice daily and trametinib orally once daily on days 1-7 and 29-56. Treatment will be repeated every 56 days until absence of disease or toxicity.
After completion of treatment, patients will be followed every 6 months for 3 years and then once a year for 2 years. The change in the immune-related overall response rate will be determined following the last treatment and safety will be assessed by the number of patients with severe side effects.
