Metastatic melanoma MedDRA version: 14.0 Level: LLT Classification code 10025651 Term: Malignant melanoma excision System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 14.0 Level: LLT Classification code 10027150 Term: Melanoma malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.0 Level: PT Classification code 10042550 Term: Superficial spreading melanoma stage II System Organ Class: 10029104
Conditions
Interventions
Product Name: MAGE-3.A1 peptide
Product Code: MAGE-3.A1
Pharmaceutical Form: Powder for suspension for injection
INN or Proposed INN: MAGE-3 Antigen (168-176) (human) Acetate
Current Sponsor code: MAG
Sponsors
Centre du Cancer des Cliniques Universitaires Saint-Luc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with histologically proven cutaneous melanoma at one of the following AJCC stages: - Regional metastatic disease (any T; N2c or N3; M0), not amenable to curative treatment by surgery or isolated limb perfusion. - Distant metastatic disease (any T; any N; M1a, M1b or M1c*). *except uncontrolled brain metastasis and except LDH >1,5ULN 2. HLA-A1 or HLA-A2 (by serology or molecular biology). 3. At least one of the two following conditions: MAGE-3 gene expression by the tumor if patient is HLA-A1 NA17 gene expression by the tumor if patient is HLA-A2 (determined by RT-PCR analysis). 4. Measurable Disease. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 31 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Uncontrolled brain or central nervous system metastasis. 2. Previous treatment for the melanoma within 6 weeks from inclusion, with any reagent known to modulate the immune system such as a cancer vaccine, interferon-alpha, interleukins or anti-CTLA-4 antibodies. 3. Previous chemotherapy, radiotherapy, corticotherapy, or other immune suppressive therapy within 4 weeks from inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and toxicity of the association of a peptide vaccine with GM-CT-01. To assess the anti-tumoral efficacy of peptide vaccine plus systemic GM-CT-01. ;Secondary Objective: To assess whether the addition of peri-tumoral injections of GM-CT-01 improves the tumor response rate To assess Time to Progression (TTP) and Overall Survival (OS). To document whether the experimental treatment induces cytolytic T lymphocyte responses to the vaccine antigens. To study anti-tumoral immunological events in tumor samples. ;Primary end point(s): Safety: Laboratory tests, vital sign measurements, physical exams and patient queries will be performed to detect new abnormalities and deteriorations of any pre-existing conditions. All clinically significant abnormalities and deteriorations should be recorded in the Case Report Forms as Adverse Events and graded according to the National Cancer Institute CTCAE v4.02 Clinical efficacy of peptide vaccine with systemic GM-CT-01: Tumor response will be assessed in accordance with the Modified RECIST version 1.1 methods and criteria.;Timepoint(s) of evaluation of this end point: Safety: Recording of adverse events the day of each peptide vaccination (days: 1, 22, 43, 64, 85, 106), the day after the first GM-CT-01 administration (day: 47) and the day of post-treatment evaluation visit (134) Laboratory tests on days: 43, 85, 134 Clinical Efficacy of Peptide vaccine with GM-CT-01 : post-treatment evaluation visit, imageries (CT-scan thorax and abdomen) and physical examination: day 134 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical Efficacy of peri-tumoral injection of GM-CT-01 : Tumor response will be assessed in accordance with the Modified RECIST version 1.1 methods and criteria. Clinical Efficacy on Survival : The Kaplan-Meier technique will be used to calculate the survival. Time to Progression (TTP) is defined as the time from first dose of study medication to progression based on RECIST1.1. Overall Survival (OS) is defined as the time from first dose of study medication to death. Subjects without evidence of progression at the end of follow-up will be considered as censored. Immune Response: CTL responses will be assessed by comparing the anti-MAGE-3.A1 and/or the anti-NA17.A2 CTLp frequency in the pre- and post-immune blood of patients vaccinated with the respective antigen(s). A positive response is defined as a =10x increase in frequency following treatment, provided that the pre-immune frequency was less than 5x10E-7. The CTLp frequency will be measured by in vitro restimulation under limiting dilution conditions, followed by staining with either the A1/MAGE-3 or A2/NA17 tetramer, respectively. Translational Research: Tumor samples will be collected before treatment in all patients. Collection of additional tumor samples under local anesthesia is allowed during and at the end of the treatment, provided that it does not interfere with the treatment or its evaluation. The analysis of immune events in situ will be reported descriptively. ;Timepoint(s) of evaluation of this end point: Clinical Efficacy of peri-tumoral injection of GM-CT-01: post-treatment evaluation visit, imageries (CT-scan thorax and abdomen) and physical examination: day 134 Clinical Efficacy on Survival: continuous by after treatment start Immune Response: day 134 Translational Research: not determined | — |
Countries
Belgium
Contacts
Public ContactJean-François BAURAIN
Cliniques Universitaires Saint-Luc
Outcome results
None listed