Phase I/II Study of Chemo-Immunotherapy Combination in Melanoma Patients (DTIC-melvacc)
Phase I/II Clinical Trial for the Evaluation of the Interaction Between Chemotherapy and Immunotherapy in Melanoma Patients
Study Overview
Status
Conditions
Intervention / 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Rome, Italy, 00133
- University Hospital Tor Vergata
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Rome, Italy, 00153
- Regina Elena Cancer Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: 2
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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.
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Active Comparator: 1
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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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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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
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one year
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
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
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two years
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Collaborators and Investigators
Sponsor
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
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Dacarbazine
Other Study ID Numbers
- ISS-DTIC-melvacc1
- 2007-006447-42
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