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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
  Purpose

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


Condition Intervention Phase
Melanoma
Biological: Melan-A
Other: Melan-A plus Dacarbazine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Clinical Trial for the Evaluation of the Interaction Between Chemotherapy and Immunotherapy in Melanoma Patients

Resource links provided by NLM:


Further study details as provided by Istituto Superiore di Sanità:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 10
Study Start Date: September 2004
Study Completion Date: September 2006
Arms Assigned Interventions
Active Comparator: 1 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
Experimental: 2 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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00559026

Locations
Italy
Regina Elena Cancer Institute
Rome, Italy, 00153
University Hospital Tor Vergata
Rome, Italy, 00133
Sponsors and Collaborators
Istituto Superiore di Sanità
Regina Elena Cancer Institute
University of Rome Tor Vergata
Investigators
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
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00559026     History of Changes
Other Study ID Numbers: ISS-DTIC-melvacc1, 2007-006447-42
Study First Received: November 15, 2007
Last Updated: November 15, 2007
Health Authority: Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on November 25, 2014