Clinical trial NCT01082887: A Study of Immunotherapy With TIL (Tumor Infiltrating Lymphocytes) in Combination With Intra-tumoral Injections of Interferon Gamma-adenovirus (Ad-IFNg) in Patients With Stage IIIc or Stage IV Metastatic Melanoma (AJCC)(Protocol TIL-Ad-INFg)
Official title: A Phase I/II Study of Immunotherapy With TIL (Tumor Infiltrating Lymphocytes) in Combination With Intra-tumoral Injections of Interferon Gamma-adenovirus (Ad-IFNg) in Patients With Stage IIIc or Stage IV Metastatic Melanoma (AJCC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Melanoma
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
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2010-03-09
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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 exclusion criteria
* Uncontrolled thyroid dysfunction
* Concurrently participation in a biomedical research (drug or radiotherapy) within the month preceding inclusion
* Metastatic lymph node stage alone with an indication of lymphadenectomy
* Brain or bone metastases discovered by radiological examination during the inclusion assessment
* Surgically resectable metastases
* Ocular melanoma
* More than one line of chemotherapy for treatment of melanoma
* Chemotherapy, immunotherapy or radiotherapy within 4 weeks before baseline (6 weeks for nitroso-ureas and mitomycin C)
* Contraindication for the use of vasopressor agents
* Treatment with molecules in pre-marketing development or whose development is finished less than 4 weeks

Primary outcomes:
measure: Clinical and biological toxicity of combined treatment TIL, IL2 et Ad-INFg
timeFrame: 12 months
Secondary outcomes:
measure: Objective response rate
timeFrame: 12 months
measure: Tumoral response
timeFrame: 12 months
measure: Progression-free survival
timeFrame: 12 months
measure: Overall survival
timeFrame: 12 months
measure: Immunological response
timeFrame: 12 months
Other outcomes:
Locations:
city: Nantes
country: France
facility: CHU de Nantes
Study officials:
affiliation: Nantes University Hospital
name: Brigitte DRENO, Profesor
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantes University Hospital
name: Gaëlle QUEREUX, Doctor
role: STUDY_CHAIR
affiliation: Nantes University Hospital
name: Anabelle BROCARD, Doctor
role: STUDY_CHAIR
References: