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Platin-based Chemotherapeutics to Enhance Dendritic Cell Vaccine Efficacy in Melanoma Patients

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02285413
First Posted: November 7, 2014
Last Update Posted: May 4, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Radboud University
  Purpose
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.

Condition Intervention Phase
Melanoma Biological: DC vaccination Biological: DC vaccination with cisplatinum Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Immunochemotherapy: Do Platin-based Chemotherapeutics Enhance Dendritic Cell Vaccine Efficacy in Melanoma Patients?

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 54
Study Start Date: February 2011
Study Completion Date: April 2016
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All patients:

  • histologically documented evidence of melanoma
  • stage III or IV melanoma according to the 2001 AJCC criteria
  • melanoma expressing gp100. Tyrosinase is not mandatory but will be assessed.
  • WHO performance status 0-1 (Karnofsky 100-70)
  • life expectancy ≥3 months
  • age 18-70 years
  • no clinical signs or symptoms of CNS metastases
  • WBC >3x10^9/l, lymphocytes >0.8x10^9/l, platelets >100x10^9/l, serum creatinine <150 µmol/l, serum bilirubin <25 µmol/l
  • normal serum LDH (<450 U/l)
  • expected adequacy of follow-up
  • no pregnant or lactating women
  • written informed consent

and in addition: Stage III melanoma

  • radical regional lymphnode dissection is performed Stage IV melanoma
  • at least one unidimensional measurable target lesions according to RECIST, not previously irradiated, and no significant symptoms of disease requiring other palliative treatments

Exclusion Criteria:

  • any prior chemotherapy, immunotherapy or radiotherapy is allowed if completed more than 4 weeks prior to planned vaccination
  • history of any second malignancy in the previous 5 years, with the exception of adequately treated basal cell carcinoma or carcinoma in situ of the cervix
  • serious active infections, known HbsAg or HIV positive, or autoimmune diseases or organ allografts
  • concomitant use of immunosuppressive drugs
  • known allergy to shell fish (since it contains KLH)
  • rapidly progressive symptomatic disease
  • any serious clinical condition that may interfere with the safe administration of DC
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02285413


Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Winette van der Graaf, professor Radboud University
  More Information

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT02285413     History of Changes
Other Study ID Numbers: NL32381.000.10
First Submitted: May 11, 2013
First Posted: November 7, 2014
Last Update Posted: May 4, 2016
Last Verified: May 2016

Keywords provided by Radboud University:
Melanoma
Dendritic cells
Cisplatin
Vaccine
Immunotherapy

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Vaccines
Cisplatin
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs