About this trial
The aim of this study is to find out whether the combination of two approved drugs, ipilimumab and nivolumab, in combination with cryoablation are safe and effective for participants who have an unresectable melanoma that is resistant, or is growing, after receiving immunotherapy with a PD-1 inhibitor.
The names of the study interventions involved in this study are:
* Cryoablation (an interventional radiology procedure that freezes part of a tumor) * Ipilimumab (an immunotherapy) * Nivolumab (an immunotherapy)
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adult patients (age > 18) with unresectable melanoma who have progressed on immune checkpoint inhibitor therapy (pembrolizumab, nivolumab, nivolumab-relatimab, atezolizumab, ipilimumab) and for whom their treating physician plans to initiate dual ICI with ipilimumab and nivolumab. Progression on adjuvant PD-1 inhibition is permitted. PD-1 does not have to be the last therapy received. This is no limited on prior lines of ICI received. There is no wash-out period required from the time of their last therapy.
Patients are medically eligible for dual checkpoint inhibition (i.e. no untreated/uncontrolled intercurrent medical issue including ongoing immune-related adverse event or need for systemic steroids >10mg PO prednisone or its equivalent, ECOG PS ≤2) with ipilimumab 3mg/kg and nivolumab 1mg/kg by their treating physician
Must have a tumor amenable to percutaneous image-guided cryoablation based on routine Interventional Radiology criteria.
Patients must have measurable disease (by RECIST) independent of the lesion to be ablated. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 11 (Measurement of Effect) for evaluation of measurable disease.
Disqualifiers
Lesion to undergo cryoablation cannot have had prior radiation therapy or other locoregional therapy
Inability to hold systemic anticoagulation prior to cryoablation (if holding anticoagulation is required by the operator)
Participants who are receiving an investigational agent(s).
Participants who are progressing on combination ipilimumab/nivolumab as their last line of therapy
Trial design
Single group
Treatments tested in this trial
Ipilimumab
DrugMonoclonal antibody administered through intravenous infusion
Nivolumab
DrugMonoclonal antibody administered through intravenous infusion
Cryoablation
Procedure/SurgeryProcedure of freezing a tumor performed via CT-guidance by interventional radiologist.
Treatment groups
Trial outcomes
Primary outcomes
Rate of Clinical Benefit
Defined as the proportion of participants with best overall response per RECIST v1.1 of confirmed complete or partial response or stable disease.
Secondary outcomes
Number of Participants with Adverse Events
Defined as all adverse events (grade 1- 5) occurring during the trial and follow-up period will be summarized using CTCAE v5.0 and the Kaplan-Meier method.
Duration of Overall Response
Defined as the time interval between the first declaration of response/stable disease and date of disease progression per RECIST v1.1 criteria and summarized using the Kaplan-Meier method.
Progression-Free Survival (PFS)
Defined as the time interval between study enrollment and documented progression of disease per RECIST v1.1 criteria and summarized using the Kaplan-Meier method.
Overall Survival (OS)
Assessed per RECIST 1.1 criteria.
Sponsors and contacts
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