Platin-based Chemotherapeutics to Enhance Dendritic Cell Vaccine Efficacy in Melanoma Patients
Condition: Melanoma
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an exploratory study and the primary objective is the immunogenicity and feasibility
      of combined chemotherapy-DC vaccination. The secondary objectives are the toxicity and
      clinical efficacy. This study will provide important data on the immunological efficacy of DC
      immunochemotherapy.
    

Detailed description: 
      1. Rationale Investigators have explored immunotherapy and have now vaccinated well over
           200 stage III and IV melanoma patients in the Netherlands with monocyte-derived
           dendritic cell (DC) vaccines and proved that DC therapy is safe with minimal side
           effects.

           Cytotoxic chemotherapy and radiotherapy have long been viewed as strategies that
           directly impact the viability of the tumor cell, and that the immune system contributed
           little to their efficacy. The commonly held opinion was that chemotherapy and
           immunotherapy could not be combined because of the myelo-suppressive effect of most
           chemotherapeutic agents. However, it becomes increasingly obvious that chemotherapy also
           possess the capacity to trigger tumor antigen release and danger signals in a manner
           that provokes engagement of innate and adaptive immunity that may be capitalized upon.

           Small proof-of-concept clinical trials in cancer patients indicate that the efficacy of
           anti-cancer vaccines may indeed be enhanced by chemotherapy [2]. Also preliminary
           observations indicate that chemotherapeutic agents, in particular platinum compounds
           (cisplatin, carboplatin and oxaliplatin) are immunogenic and may contribute to reverse
           tumor cell induced immunosuppression/immune deviation.

           Investigators hypothesize that DC vaccination, when combined with other more
           conventional anti-tumor treatments such as chemotherapy, that eradicate large numbers of
           cancer cells, may allow the T cells to clear the remaining cancer cells and to provide
           immunological memory to prevent relapse.

        2. Objectives This is an exploratory study and the primary objective is the immunogenicity
           and feasibility of combined chemotherapy-DC vaccination. The secondary objectives are
           the toxicity and clinical efficacy. This study will provide important data on the
           immunological efficacy of DC immunochemotherapy.

        3. Study design This study is an open label randomized phase II study.

        4. Study population Our study population consists of melanoma patients, with expression of
           melanoma associated tumor antigens gp100 and tyrosinase. Melanoma patients with regional
           lymph node metastasis in whom a radical lymph node dissection is performed within 2
           months of inclusion in this study (further referred to as stage III) and melanoma
           patients with measurable distant metastases (further referred to as stage IV) will be
           included.

        5. Main study endpoints The primary objective of the study is to investigate the
           immunogenicity and feasibility of combined chemotherapy-DC vaccination. The secondary
           objective is to investigate the toxicity and clinical responses (only in stage IV) upon
           DC immunochemotherapy.
    

Intervention name(s): DC vaccination; DC vaccination with cisplatinum
Intervention type(s): Biological; Biological
Intervention description(s): DC vaccination without cisplatinum; DC vaccination with cisplatinum
Intervention MeSH terms: Cisplatin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Melanoma; Dendritic cells; Cisplatin; Vaccine; Immunotherapy