To evaluate safety and the effect of isolated limb perfusion together with nivolumab as a way to increase efficacy and give further insights in early immunological mechanisms. In the first phase Ib part, 20 patients will be enrolled and followed for a minimum of 3 months. An independent data safety monitoring board (DSMB) will continuously review safety and judge the seriousness of the events and also recommend the study to stop if necessary. If the DSMB do not find safety issues, the trial will continue as a phase II trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
74
One infusion of nivolumab (Opdivo®) 480mg (flat dose) in NaCl (Natriumklorid Baxter Viaflo, 9 mg/ml) during 60 minutes
Patients will be treated with ILP according to clinical routine at each separate site. The procedure is performed under general anaesthesia. The major artery and vein of the limb is catheterized, and a tourniquet is placed proximally on the limb. Continuous leakage monitoring is performed. The perfusate is heated to 40C and after ensuring steady state, melphalan (Alkeran®) at a dose of 13 mg/L (upper limb) or 10 mg/L (lower limb) is infused into the circulation during 20 minutes for a total perfusion time of 60 minutes. According to local routine tasonermin (Beromun®) will be added to the perfusate 30 minutes before the melphalan as a bolus dose of 1-4 mg.
Netherlands Cancer Institute
Amsterdam, Netherlands
RECRUITINGErasmus MC Cancer Institute
Groningen, Netherlands
NOT_YET_RECRUITINGErasmus MC Cancer Institute
Rotterdam, Netherlands
NOT_YET_RECRUITINGSahlgrenska University Hospital
Gothenburg, Sweden
RECRUITINGComplete response rate (CR)
To evaluate if melphalan based isolated limb perfusion (ILP) synergizes with nivolumab in inducing complete responses (CR) at 3 months after treatment in melanoma patients with in-transit metastasis.
Time frame: 3 months
Time to local progression (TTLP)
Evaluation of local progression-free survival (LPFS). LPFS is defined as the number of months from the date of ILP to the date of the first documented disease recurrence or progression in the treated area (defined as the area below the tourniquet used for ILP). LPFS will be determined based on clinical assessments according to RECIST version 1.1 criteria.
Time frame: 36 months
Distant metastases-free survival (DMFS)
Evaluation of DMFS, defined as the number of months from the date of ILP to the date of the first documented distant disease recurrence.
Time frame: 36 months
Progression-free survival (PFS)
Evaluation of PFS, defined as the number of months from the date of ILP to the date of the first documented disease recurrence or progression at any site.
Time frame: 36 months
Melanoma specific survival (MSS)
Evaluation of melanoma specific survival (MSS), MSS is calculated as the time from date of treatment to date of death due to any cause. Both median MSS and the per cent of patients alive at 36 months will be evaluated.
Time frame: 36 months
Overall survival (OS)
Evaluation of overall survival (OS), OS is calculated as the time from date of treatment to date of death due to any cause. Both median OS and the per cent of patients alive at 36 months will be evaluated.
Time frame: 36 months
Quality of life measured by FACT-M
Quality of life (QoL) by FACT-M. Change from baseline for all subscales as well as for the total scores.
Time frame: 36 months
Quality of life measured by EQ-5D
Quality of life (QoL) by EQ-5D measured as the change from baseline
Time frame: 36 months
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