NCT00559026

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Istituto Superiore di Sanità · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

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.

Conditions

• Melanoma

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2004-09-01
• Completion: 2006-09-01
• First posted: 2007-11-16
• Last updated: 2007-11-16

Locations

2 sites across 1 country: Italy