Efficacy of Immunotherapy in Melanoma Patients With Brain Metastases Treated With Steroids
This clinical trial is to clarify whether treatment with a checkpoint inhibitor alone (pembrolizumab) or two in combination (ipilimumab and nivolumab), results in clinical benefit for MM patients with brain metastases and in need of steroid treatment. Patients will be treated in four arms depending on steroid dose level at inclusion (\> 10 \< 25 mg prednisolone or \> 25 mg prednisolone) and treatment (pembrolizumab alone or the combination of ipilimumab and nivolumab).
• Histologically confirmed metastatic melanoma with radiologically verified brain metastasis
• Need for systemic steroid treatment (prednisolone \> 10 mg daily; dexamethasone \> 1.6 mg daily, hydrocortisone \> 40 mg daily or equivalent) due to brain metastasis
• At least one measurable lesion according to RECIST version 1.1 guidelines
• Evaluable intracranial disease
• 18 years of age or older
• Performance status 0-2
• Able to undergo MRI with gadolinium contrast agent
• Adequate hematological and organ function
• No significant toxicity from previous cancer treatments (CTC\<1)
• Women of childbearing potential: Negative serum pregnancy test and must use effective contraception. This applies from screening and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered effective contraceptives
• Men with female partner of childbearing potential must use effective contraception from screening and until 6 months after treatment. Effective contraceptives are as described above for the female partner. In addition documented vasectomy and sterility or double barrier contraception are considered effective contraceptives
• Signed statement of consent after receiving oral and written study information.
• Willingness to participate in the planned treatment and follow-up and capable of handling toxicities.
• For arm E specifically: Tumor cells must harbor BRAF mutation.