Metastatic Melanoma
Conditions
Keywords
Immunotherapy TIL (Tumor Infiltrating Lymphocytes), Intra-tumoral injection, Interferon gamma-adenovirus(Ad-IFNg), Metastatic melanoma, A stage IIIc/IV metastatic melanoma with nodal relapse, in transit metastasis, cutaneous unresectable metastases, visceral metastases
Brief summary
The main objective of this study is to evaluate the clinical and biologic toxicity of cell therapy by adoptive transfer of TIL in combination with intra-tumoral injections of Ad-INFg.
Interventions
OTHERTIL-Ad-INFg
After verification of inclusion and non-inclusion criteria and after obtaining informed consent from the patients, a tumor sample will be taken for sterile production of TIL. Patients will receive intra-tumoral injections of Ad-INFg every 15 days from J-15 to M2, then every month from M3 to M11 or until disease progression. The Ad-INFg will be administered by intra-tumoral injection at a dose of 5x1010 vp (viral particles) per lesion. A maximum of 6 lesions will be treated simultaneously. They will also receive two infusion of TIL at M0 (Cycle 1) and M1 (Cycle 2) by intravenous infusion lasting 30 to 65 minutes followed by subcutaneous injections of IL2 from J1 to J5 and from J8 to J12 of each cycle.An evaluation of injected and not injected tumoral lesions including photographs will be realised at the pre-inclusion visit, J-15, M0 and every month until M12.
Sponsors
Nantes University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Pre-Inclusion Criteria: * Male or female patients ≥ 18 and ≤ 75 years of age * Patients must have signed informed consent * A negative pregnancy test for women with childbearing potential * Patients with stage IIIc/IV metastatic melanoma (AJCC 6th edition) with nodal relapse, in transit metastasis, unresectable cutaneous metastases, visceral metastases except bone and brain metastases * Presence of at least one lesion accessible for intra-tumoral injections of Ad-IFNg * A negative brain scan, eliminating any brain metastases * ECOG performance status of 0-2 * Adequate bone-marrow reserve, renal function and hepatic function as assessed by standard laboratory criteria * Subjects affiliated to an appropriate social security system Inclusion Criteria: * Negative viral serology (HIV ½, p24 Ag, HTLV 1 / 2, B and C hepatitis)
Exclusion criteria
* For female : the patient is pregnant or lactating or not using contraception and proved by a negative pregnancy test * Positive viral serology for HIV ½, p24 Ag, HTLV 1 / 2 or B and C hepatitis * History or current manifestations of severe progressive heart disease (congestive heart failure, coronary artery disease, uncontrolled arterial hypertension, serious rhythm disorders or ECG signs of previous myocardial infarction) * Any serious illness, acute or chronic, e.g. active infection requiring antibiotics, bleeding disorders or any other condition that requires concomitant medications not allowed during this study * Presence of a second active cancer except in situ cervical cancer or skin carcinoma * Intercurrent disease requiring a corticosteroid treatment or a treatment with interferon-α * Any autoimmune disease including active diabetes mellitus or immunodeficiency. Vitiligo in not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical and biological toxicity of combined treatment TIL, IL2 et Ad-INFg | 12 months | The evaluation of clinical and biological toxicity of combined treatment including infusion of TIL associated with subcutaneous injections of low-doses of IL-2 and intra-tumoral injections of Ad-IFNg will be performed according to clinical and biological criteria defined by NCI (Common Toxicity Criteria - version 3.0, August 2006). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | 12 months | The evaluation of the objective response rate |
| Tumoral response | 12 months | The evaluation of the tumoral response of injected lesions every month |
| Progression-free survival | 12 months | The evaluation of the progression-free survival, |
| Overall survival | 12 months | The evaluation of the overall survival |
| Immunological response | 12 months | The evaluation of the immunological response |
Countries
France
Outcome results
None listed