A Phase II Study of the Combination of Ipilimumab and Fotemustine in Patients With Unresectable Locally Advanced or Metastatic Malignant Melanoma
Immunotherapy, chemotherapy and chemotherapy combinations are currently the most effective
accepted systemic treatments for metastatic melanoma. However, significant and prolonged
responses are rare.
The trial will determine the additional benefit achieved from adding fotemustine to the
anti-CTLA-4 monoclonal antibody,ipilimumab .
It is assumed that the mechanism by which ipilimumab augments the effects of chemotherapy in
animal models relies on the ability of the cytotoxic agent to induce apoptosis of tumor
cells. These apoptotic cells then can function as potent inducers of an immune response
against any non-tolerized antigen that they contain. Thus, the chemotherapy may be creating
an in vivo autologous tumor vaccine. Ipilimumab prevents the down regulation of this immune
response, allowing for tumor rejection. Animal models evaluating the combination of
anti-CTLA4 antibody and chemotherapy have given only a brief acute treatment with
chemotherapy - presumably adequate to induce some tumor apoptosis, but inadequate to induce
significant prolonged tumor rejection.
Since patients with metastatic melanoma generally require therapy within a relatively short
period of time, this protocol will allow for the use of fotemustine. Standard dosing of
fotemustine will be used to optimize the chance for tumor control.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The immune response disease control rate (irDCR) using the immune-related (ir) tumor response criteria of the combination of ipilimumab and fotemustine in patients with unresectable locally advanced or metastatic melanoma.
Immune-related Disease Control Rate (irDCR) is the proportion of treated subjects with a BOR of confirmed irCR, confirmed irPR or irSD. Tumor assessment (including determination of overall response at each tumor assessment and best overall response (BOR) taken over all tumor assessments prior to subsequent therapy is performed using the immune-related (ir) tumor response criteria.
Michele Maio, MD, PhD
Medical Oncology and Immunotherapy Unit, University Hospital of Siena
Italy: The Italian Medicines Agency