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)

NCT ID: NCT01082887

Last Updated: 2016-08-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2012-10-31

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.

Conditions

Metastatic Melanoma

Study Design

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

Study Groups

TIL-Ad-INFg

Group Type: EXPERIMENTAL

TIL-Ad-INFg

Intervention Type: OTHER

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.

Interventions

TIL-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.

Intervention Type: OTHER

Eligibility Criteria

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

• 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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brigitte DRENO, Profesor

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Gaëlle QUEREUX, Doctor

Role: STUDY_CHAIR

Nantes University Hospital

Anabelle BROCARD, Doctor

Role: STUDY_CHAIR

Nantes University Hospital

Locations

CHU de Nantes

Nantes, , France

Countries

France

Other Identifiers

2009-013087-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BRD/09/05-R

Identifier Type: -

Identifier Source: org_study_id