Phase I/II Study of Chemo-Immunotherapy Combination in Melanoma Patients (DTIC-melvacc)

This study has been completed.
Sponsor:
Collaborators:
Regina Elena Cancer Institute
University of Rome Tor Vergata
Information provided by:
Istituto Superiore di Sanità
ClinicalTrials.gov Identifier:
NCT00559026
First received: November 15, 2007
Last updated: NA
Last verified: November 2007
History: No changes posted

November 15, 2007
November 15, 2007
September 2004
Not Provided
Assessment of safety by evaluating local and systemic adverse reactions during the trial. Assessment of the vaccine-specific cellular immune responses [ Time Frame: one year ]
Same as current
No Changes Posted
Assessment of relapse-free survival and overall survival calculated from the time of the first chemotherapy/vaccine injection. Evaluation by microarray analysis of the gene expression profiles of patients PBMC 24 h after DTIC administration. [ Time Frame: two years ]
Same as current
Not Provided
Not Provided
 
Phase I/II Study of Chemo-Immunotherapy Combination in Melanoma Patients
Phase I/II Clinical Trial for the Evaluation of the Interaction Between Chemotherapy and Immunotherapy in Melanoma Patients

This phase I/II study is directed at evaluating safety and immunogenicity of a melanoma peptide vaccine in combination or not with Dacarbazine administration in melanoma patients

Recently, it is becoming increasingly accepted that, in order to induce a clinically effective antitumor response, immunotherapy needs to be combined with chemotherapy. Thus, the traditional perception that chemotherapy and immunotherapy act through unrelated mechanisms which may be antagonistic is challenged on the premises that a selected panel of drugs can induce an immunogenic cell death producing specific danger signals. Furthermore, chemotherapy combined to immunotherapy may affect antigen cross-presentation, induce a "cytokine storm", reduce the number of regulatory T cells and activate homeostatic lymphoid proliferation. Our previous results obtained in a mouse model, demonstrated that drug-induced cytokines can favour antitumor immunity. Based on this observation, we explored whether the administration of dacarbazine (DTIC) in disease-free melanoma patients in combination with peptide vaccination could result into an improved anti tumor immune response.

Patients included in the study were assigned to two treatment arms either receiving anti-tumor vaccination with Melan-A and gp100 analog peptides alone (arm 1) or in combination with DTIC pre-treatment (arm 2).

Arm 1, vaccine alone: patients received i.d. injections of Melan-A: 26-35 (A27L) and gp100: 209-217 (210M) peptides (250 µg each) formulated in Montanide ISA-51 plus s.c. injection of 3MU IFN-α, as an adjuvant on day 1 and 8 every 21 days for a total of 5 courses (10 vaccinations). Both peptides and IFN-α were injected in close but separate sites next to local lymph nodes.

Arm 2, DTIC plus vaccine: the same vaccination schedule was combined with DTIC (800 mg/mq i.v.) administered one day before each vaccine administration according to the standard treatment.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
  • Biological: Melan-A
    i.d. injections of Melan-A: 26-35 (A27L) and gp100: 209-217 (210M) peptides (250 µg each) formulated in Montanide ISA-51 plus s.c. injection of 3MU IFN-α, as an adjuvant on day 1 and 8 every 21 days for a total of 5 courses
  • Other: Melan-A plus Dacarbazine
    Dacarbazine plus vaccine: the vaccination schedule as in arm 1 was combined with DTIC (800 mg/mq i.v.) administered one day before each vaccine administration according to the standard treatment.
  • Active Comparator: 1
    Intervention: Biological: Melan-A
  • Experimental: 2
    Intervention: Other: Melan-A plus Dacarbazine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
September 2006
Not Provided

Inclusion Criteria:

  • histologically proven diagnosis of melanoma stage II, III, and IV without clinical/radiological evidence of disease
  • Age >18 years
  • life expectancy of more than 6 months
  • ECOG performance status of 0-2
  • adequate blood cell counts and kidney-liver function
  • use of adequate contraceptive methods
  • signed informed consent

Exclusion Criteria:

  • concomitant or previous history of malignant disease, except for in situ cervical carcinoma or non melanomatous skin cancer
  • severe cardiovascular disease
  • clinically active infections and/or significant autoimmune diseases
  • concomitant or previous (within 6 weeks) treatment with immunosuppressive drugs
  • previous treatments with chemotherapy and/or interferon alpha or beta within 4 weeks and/or radiotherapy within 6 weeks an/or biological therapy within 8 weeks before starting vaccination
  • psychiatric illness interfering with patient compliance, pregnancy or lactation
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
NCT00559026
ISS-DTIC-melvacc1, 2007-006447-42
Yes
Not Provided
Istituto Superiore di Sanità
  • Regina Elena Cancer Institute
  • University of Rome Tor Vergata
Principal Investigator: Virginia Ferraresi, M.D. Regina Elena Cancer Institute
Principal Investigator: Mario Roselli, M.D. University of Rome Tor Vergata
Study Director: Enrico Proietti, M.D. Istituto Superiore di Sanità
Istituto Superiore di Sanità
November 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP