This is a single center non-blinded randomized multi-cohort non-comparative phase II trial with a Simon's two-stage design.
In the first stage, 13 evaluable patients will be accrued per cohort. Evaluable is defined as: at least one administration of nivolumab and availability of paired biopsies for immunohistochemistry (for induction treatment cohorts pre-induction and pre-nivolumab biopsies). If there are 1 or no responses observed in these 13 patients, the cohort will be stopped. Otherwise, 21 additional patients will be accrued for a total of 34.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
52
Antoni van Leeuwenhoek
Amsterdam, Netherlands
RECRUITINGProgression free survival
Time from randomization to date of first tumor progression
Time frame: assessed monthly until progression or date of death; median 12 months
Overall response rate
complete response or partial response according to iRECIST and RECIST1.1
Time frame: assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months
Clinical benefit rate
Beneficial response (complete response, partial response or stable disease) according to RECIST 1.1 and iRECIST
Time frame: assessed at week 6, 12 and 20 and every 8 weeks thereafter; assessed up to 120 months
Overall survival
time from nivolumab initiation to death from any cause
Time frame: assessed monthly until date of death; median 12 months
Toxicity of all study regimens
adverse events will be graded according to NCI Common Toxicity Criteria v 5.0
Time frame: assessed until 100 days after of treatment end
Progression Free Survival after 6 cycles
the number of patients free of progression after 6 cycles of nivolumab
Time frame: time from nivolumab initiation to tumor progression or death from any cause; assessed up to 120 months
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