Phase I/II Study of Chemo-Immunotherapy Combination in Melanoma Patients

Melanoma Clinical Trial

— DTIC-melvacc  

Official title:

Phase I/II Clinical Trial for the Evaluation of the Interaction Between Chemotherapy and Immunotherapy in Melanoma Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00559026
• Other study ID #: ISS-DTIC-melvacc1
• Secondary ID: 2007-006447-42
• Status: Completed
• Phase: Phase 1
• First received: November 15, 2007
• Last updated: November 15, 2007
• Start date: September 2004
• Est. completion date: September 2006

Study information

• Verified date: November 2007
• Source: Istituto Superiore di Sanità
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma

Intervention

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-a, 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.

Locations

Country	Name	City	State
Italy	Regina Elena Cancer Institute	Rome
Italy	University Hospital Tor Vergata	Rome

Sponsors (3)

Lead Sponsor	Collaborator
Istituto Superiore di Sanità	Regina Elena Cancer Institute, University of Rome Tor Vergata

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of safety by evaluating local and systemic adverse reactions during the trial. Assessment of the vaccine-specific cellular immune responses		one year
Secondary	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.		two years