This is a dose-seeking and efficacy study of combined BRAF Inhibitor Vemurafenib and High-dose Interferon alfa-2b for therapy of advanced melanoma.
Name: High-dose Interferon alfa-2b
Description: •Vemurafenib at standard dosing with a 2 week lead-in period to identify potential effects. IFNα-2b following this (week 2 onwards) at standard induction (4 weeks) and maintenance (48 weeks) doses.Type: DrugVemurafenib + IFNα-2b (10 MU/m2/d) Vemurafenib + IFNα-2b(15 MU/m2/d) Vemurafenib + IFNα-2b (20 MU/m2/d)
Name: Vemurafenib
Description: Vemurafenib is a prescription medicine used to treat melanoma, that has spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal "BRAF" gene.Type: DrugVemurafenib + IFNα-2b (10 MU/m2/d) Vemurafenib + IFNα-2b(15 MU/m2/d) Vemurafenib + IFNα-2b (20 MU/m2/d)
Description: At each dose level, the number of patients experiencing Adverse Events over their course of treatment will be characterized by type of Adverse Event and grade using NCI CTCAE (v4.0), and by time of onset in relation to the first day of therapy.
Measure: Number of Participants with Adverse Events to determine Ph II dose Time: 12-24 months from study startDescription: •Progression Free Survival will be evaluated at 6 months using the Kaplan-Meier method. Overall Survival will be measured from the initial date of treatment to the recorded date of death, and analyzed similarly to Progression Free Survival. Overall Survival will also be analyzed with the Kaplan-Meier method. The complete response rate and partial response rate will be estimated by the proportion of patients with a best response respectively by RECIST criteria.
Measure: Progression Free and overall survival (Efficacy) Time: 48 monthsDescription: Melanoma metastases removed from patients pretreatment, post-BRAFI alone and Post B-RAF+ will be analyzed for expression of IFNAR1 and immunologically relevant molecules such as HLA antigens, APM components and MA; these results will be correlated with T cell infiltration. In addition the metastases will be tested for extent of melanoma cell proliferation and apoptosis.
Measure: Improve tumor STAT signaling Time: 48 monthsAllocation: Non-Randomized
Single Group Assignment
There are 2 SNPs
- BRAF V600E and V600K mutated - Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised. --- V600E ---
- BRAF V600E and V600K mutated - Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised. --- V600E --- --- V600K ---