Phase I clinical trial for Dabrafenib in patients with brain metastases from melanoma

This study was a phase I clinical trial that tested the safety and efficacy of Dabrafenib in melanoma patients with brain metastases (melanoma that has spread to the brain). Results showed that the drug had manageable side effects and improved progression-free survival.

Metastatic melanoma means that the cancer has spread from its original location to distant lymph nodes or other organs of the body such as the liver, lungs or brain. Brain metastases have a poor prognosis for melanoma patients because they are more aggressive and difficult to treat. Treatment options for these patients include surgical procedures, radiation therapy (whole brain radiation, stereotactic radiosurgery), chemotherapy, combination therapies or experimental drugs. Dabrafenib is an experimental targeted (biological) therapy drug that blocks a specific protein (BRAF), produced as the result of a genetic mutation – BRAF mutation. About 50% of melanomas have this genetic defect in the BRAF protein and may respond to Dabrafenib treatment.

This clinical trial included 184 patients, of which 156 had metastatic melanoma with BRAF mutations. Patients received progressive doses of dabrafenib daily (from 12 mg once a day to 300 mg twice daily) to determine the proper dose for phase II clinical trial testing. Parameters measured were safety and treatment-related side effects, as well as response to treatment and progression-free survival, or PFS (defined as the period of time without cancer progression). 

The most common side effects were cutaneous squamous-cell carcinoma (a form of skin cancer caused by an abnormal growth of the cells from the most superficial layer of the skin – the epidermis) in 11% of patients, tiredness (14.8% of patients) and fever (11.6% of patients).  76% of patients (140) had mild or no treatment-related side effects. The recommended dose for phase II clinical trial testing was 150 mg dabrafenib twice daily. 69% of patients had a partial or complete response to treatment with dabrafenib. 47% of patients did not have disease progression for 6 months, with a PFS of 4.1 to 8.3 months. Also, 9 out of 10 patients with brain metastases from melanoma had smaller brain lesions after treatment with dabrafenib. 

In conclusion, this study suggests dabrafenib is safe and has manageable side effects, showing good results in patients with brain metastases from melanoma.

Dabrafenib is not yet approved by the US FDA. This is only a phase I clinical trial on a small group of patients. Future phase II and III trials are expected in order to determine dabrafenib’s therapeutic potential in patients with metastatic melanoma.

This study was funded by GlaxoSmithKline Pharmaceuticals, the manufacturer of dabrafenib.