This phase 2 trial aims to test the effectiveness of the combined treatment of three different immunotherapies. The main outcomes of this trial will be the tumor response to the treatment and the overall survival.
Immunotherapies stimulate the immune system to attack and kill cancer cells the way it would a virus or bacteria. The combination of different immunotherapies may improve the melanoma outcomes in patients with metastatic (spread to other parts of the body) melanoma.
The current trial will examine the immune response caused by different combinations of nivolumab (Opdivo), dabrafenib (Tafinlar) and trametinib (Mekinist). The main outcome to be measured will be the response of the tumor to the treatment and the overall survival of the patients.
Who are they looking for?
This trial will recruit 60 participants with stage 4 melanoma or stage 3 that cannot be surgically removed. Patients must have normal organ function and blood levels. Patients must not have any active severe disease, such as lung or liver disease, autoimmune disease, hepatitis or HIV. Women must not be pregnant or breastfeeding. All participants must be willing to use contraception if pregnancy is a possibility.
How will it work
Patients will be assigned to different groups of treatment according to their tumor mutation (permanent change) type. The BRAF-mutated group will receive nivolumab, dabrafenib and trametinib. Patients in the RAS-mutated (or BRAF-negative) group will receive nivolumab and trametinib.
All participants will receive nivolumab by injection over 30 minutes on days 1 and 15 and trametinib capsules once every day. Patients in the BRAF group will receive dabrafenib capsules twice every day. The treatment will continue until disease progression or severe side effects. Patients will be followed-up every 3 months for 3 years. Follow-up will include CT and/or MRI scans, blood tests, physical exams, eye exams, and heart function tests.