Platin-based Chemotherapeutics to Enhance Dendritic Cell Vaccine Efficacy in Melanoma Patients
|ClinicalTrials.gov Identifier: NCT02285413|
Recruitment Status : Completed
First Posted : November 7, 2014
Last Update Posted : May 4, 2016
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Biological: DC vaccination Biological: DC vaccination with cisplatinum||Phase 2|
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 . 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.
- 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.
- Study design This study is an open label randomized phase II study.
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Immunochemotherapy: Do Platin-based Chemotherapeutics Enhance Dendritic Cell Vaccine Efficacy in Melanoma Patients?|
|Study Start Date :||February 2011|
|Primary Completion Date :||October 2015|
|Study Completion Date :||April 2016|
Experimental: DC vaccination
mature DC injected intradermally and intravenously loaded with mRNA encoding tumor-associated antigens gp100 and tyrosinase
Biological: DC vaccination
DC vaccination without cisplatinum
Experimental: DC vaccination with cisplatinum
mature DC injected intradermally and intravenously loaded with mRNA encoding tumor-associated antigens gp100 and tyrosinase. each DC vaccine will be preceded by cisplatin infusion: 50 mg/m2, 1-2h before DC injection.
Biological: DC vaccination with cisplatinum
DC vaccination with cisplatinum
- Immunogenicity: number of participants with KLH and/or tumor-specific antigens immune responses. [ Time Frame: 5 years ]
- Feasibility: % of vaccines meeting the release criteria. [ Time Frame: 5 years ]
- Toxicity: number of Participants with Adverse Events. [ Time Frame: 5 years ]
- Progression-free survival [ Time Frame: 5 years ]
- Overall survival [ Time Frame: 5 years ]
- Best objective response (only in stage IV) [ Time Frame: 5 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02285413
|Radboud University Nijmegen Medical Centre|
|Nijmegen, Gelderland, Netherlands, 6500 HB|
|Principal Investigator:||Winette van der Graaf, professor||Radboud University|