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

NCT ID: NCT00559026

Last Updated: 2007-11-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-30
• Study Completion Date: 2006-09-30

Brief 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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: ACTIVE_COMPARATOR

Melan-A

Intervention Type: BIOLOGICAL

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

2

Group Type: EXPERIMENTAL

Melan-A plus Dacarbazine

Intervention Type: OTHER

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.

Interventions

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

Intervention Type: BIOLOGICAL

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.

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regina Elena Cancer Institute

OTHER

Sponsor Role: collaborator

University of Rome Tor Vergata

OTHER

Sponsor Role: collaborator

Istituto Superiore di Sanità

OTHER

Sponsor Role: lead

Principal Investigators

Virginia Ferraresi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Regina Elena Cancer Institute

Mario Roselli, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Rome Tor Vergata

Enrico Proietti, M.D.

Role: STUDY_DIRECTOR

Istituto Superiore di Sanità

Locations

University Hospital Tor Vergata

Rome, , Italy

Regina Elena Cancer Institute

Rome, , Italy

Countries

Italy

Other Identifiers

2007-006447-42

Identifier Type: -

Identifier Source: secondary_id

ISS-DTIC-melvacc1

Identifier Type: -

Identifier Source: org_study_id