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)

NCT01082887 | Terminated Phase 1 DMC

• 2 other identifiers: BRD/09/05-R2009-013087-38
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Objective response rate

  12 months

• Tumoral response

  12 months

• Progression-free survival

  12 months

• Overall survival

  12 months

• Immunological response

  12 months

Study Arms (1)

TIL-Ad-INFg

EXPERIMENTAL

Other: TIL-Ad-INFg

Interventions

TIL-Ad-INFg 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.

TIL-Ad-INFg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• Metastatic lymph node stage alone with an indication of lymphadenectomy
• 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

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

CHU de Nantes

Nantes, 44093, France

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Brigitte DRENO, Profesor

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

• Gaëlle QUEREUX, Doctor

  Nantes University Hospital

  STUDY CHAIR

• Anabelle BROCARD, Doctor

  Nantes University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2010
• First Posted: March 9, 2010
• Study Start: January 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: August 8, 2016

Record last verified: 2016-08

Locations

FR (1)