This is a single center non-blinded randomized non-comparative phase II trial. The first stage of the trial consists of five arms ( with induction treatment followed by nivolumab, 1 with no induction treatment before nivolumab). For the second stage, the number of arms will be reduced based on the results obtained in the first stage.
Triple negative breast cancer (TNBC) patients have a relatively high relapse rate and upon relapse the median overall survival is less than a year. No targeted therapies are currently available for this subgroup. Compared to other breast cancer subtypes, the percentage of tumor-infiltrating lymphocytes (TILs) is significantly higher in TNBC. Given the durable responses induced by the immune checkpoint inhibitor nivolumab in other advanced solid cancers, immunotherapeutic approaches, such as blockade of PD-1 by nivolumab may be the key to treat TNBC. Moreover, since classical anticancer agents can stimulate immune effector cells, the investigators hypothesize that short-term induction treatment with radiation, doxorubicin, cyclophosphamide or cisplatin induces an anticancer immune response resulting in synergistic activity with nivolumab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
nivolumab 3 mg/kg, every 2 weeks after induction treatment
20 Gy to metastatic lesion
15 mg flat dose, once weekly for 2 weeks
Antoni van Leeuwenhoek
Amsterdam, Netherlands
Progression free survival
Time from randomization todate of first tumor progression
Time frame: assessed monthly until progression; median 12 months
Overall response rate
complete response or partial response at 12 weeks and 6 months
Time frame: At 12 weeks and 6 months
Clinical benefit rate
Beneficial response (complete response, partial response or stable disease) at 6 months
Time frame: At 6 months
Toxicity of all study regimens
adverse events will be graded according to NCI Common Toxicity Criteria v 4.0
Time frame: assessed until 100 days after of treatment end
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metronomic schedule, 50 mg daily orally for 2 weeks
40 mg/m2, weekly for 2 weeks