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)

Metastatic Melanoma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01082887
• Other study ID #: BRD/09/05-R
• Secondary ID: 2009-013087-38
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: March 8, 2010
• Last updated: August 5, 2016
• Start date: January 2010
• Est. completion date: October 2012

Study information

• Verified date: August 2016
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France : AFSSAPS
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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-a

• 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenoviridae Infections
• Melanoma
• Metastatic Melanoma

Intervention

Other:
• 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.

Locations

Country	Name	City	State
France	CHU de Nantes	Nantes

Sponsors (1)

Lead Sponsor	Collaborator
Nantes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical and biological toxicity of combined treatment TIL, IL2 et Ad-INFg	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).	12 months	Yes
Secondary	Objective response rate	The evaluation of the objective response rate	12 months	No
Secondary	Tumoral response	The evaluation of the tumoral response of injected lesions every month	12 months	No
Secondary	Progression-free survival	The evaluation of the progression-free survival,	12 months	No
Secondary	Overall survival	The evaluation of the overall survival	12 months	Yes
Secondary	Immunological response	The evaluation of the immunological response	12 months	No