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).
Cancer immunotherapy with checkpoint inhibitors (CPI) has demonstrated significant response rates, with clinical responses of exceptional duration observed in pivotal clinical trials for multiple types of solid tumors. Results from clinical trials demonstrate a considerable survival benefit of CPI over standard treatments, leading to registration of CPI for lung-, head and neck-, bladder-, renal cancer, lymphomas and metastatic melanoma (MM). To date, CPI appear to hold the key for longterm survival - at least for patients treated in clinical trials. Patients enrolled in pivotal clinical trials for immunotherapy of MM are highly selected and does not include patients with brain metastases. Small phase II studies lend support to CPI to yield responses in melanoma that has metastasized to the brain. However, a large proportion of patients that develop brain metastasis will require continued systemic treatment with steroids to alleviate symptoms from the central nervous system (CNS). This group of patients are not offered treatment with CPI, as it is generally assumed that steroid treatment hamper their clinical efficacy. Thus, this group of patients face a large unmet need. Due to the immune inhibiting effects, steroids are used to manage immune-related adverse events (irAEs) induced by CPI treatment. However, patients receiving steroids in this context are still able to achieve and maintain clinical benefit even after stopping treatment. It is not known whether steroid treatment at the time of initiation of CPI treatment diminishes the treatment effect, as patients in need of steroid treatment are generally excluded from clinical trials.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Alone
In combination with nivolumab.
In combination with ipilimumab.
Herlev Universityhospital
Herlev, Capital Region, Denmark
RECRUITINGAarhus Universityhospital
Aarhus, Midt, Denmark
NOT_YET_RECRUITINGOdense Universityhospital
Odense, Syd, Denmark
NOT_YET_RECRUITING6 months progression-free survival rate
Proportion of patients who did not progress or die within 6 months from commencing study treatment.
Time frame: 6 months
6 months overall survival rate
Proportion of patients who did not die within 6 months from commencing study treatment.
Time frame: 6 months
Overall progression-free survival
Time from commencing study treatment to the date of progression or death.
Time frame: 4 years
Overall survival
Time from commencing study treatment to the date of death from any cause.
Time frame: 4 years
Overall response rate
Proportion of patients with an overall complete or partial response according to modified RECIST 1.1.
Time frame: 4 years
Extracranial response rate
Proportion of patients with an overall complete or partial response in extracranial lesions according to modified RECIST 1.1.
Time frame: 4 years
Intracranial response rate
Proportion of patients with an overall complete or partial response in intracranial lesions according to modified RECIST 1.1.
Time frame: 4 years
Intracranial clinical benefit rate
Proportion of patients with an overall complete, partial response or stable disease \> 6 months according to modified RECIST 1.1.
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In combination with binimetinib
In combination with encorafenib
In combination with dabrafenib
In combination with trametinib
Time frame: 4 years
Blood and tissue biomarkers of response and progression
Correlation of the baseline PD-L1 status, immune markers, genomics and other biomarkers in tumour tissue and blood with complete or partial response and at subsequent disease progressionanalyses of potential specific biomarkers predictive of response or progression.
Time frame: 5 years