Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital
ClinicalTrials.gov Identifier:
NCT01082887
First received: March 8, 2010
Last updated: June 11, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Metastatic Melanoma
Other: TIL-Ad-INFg
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Nantes University Hospital:

Primary Outcome Measures:
  • Clinical and biological toxicity of combined treatment TIL, IL2 et Ad-INFg [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • Objective response rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The evaluation of the objective response rate

  • Tumoral response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The evaluation of the tumoral response of injected lesions every month

  • Progression-free survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The evaluation of the progression-free survival,

  • Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The evaluation of the overall survival

  • Immunological response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The evaluation of the immunological response


Enrollment: 18
Study Start Date: January 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TIL-Ad-INFg 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01082887

Locations
France
CHU de Nantes
Nantes, France, 44093
Sponsors and Collaborators
Nantes University Hospital
Investigators
Principal Investigator: Brigitte DRENO, Profesor CHU de Nantes
Study Chair: Gaëlle QUEREUX, Doctor CHU de Nantes
Study Chair: Anabelle BROCARD, Doctor CHU de Nantes
  More Information

No publications provided

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT01082887     History of Changes
Other Study ID Numbers: 09/5-R, 2009-013087-38
Study First Received: March 8, 2010
Last Updated: June 11, 2013
Health Authority: France : AFSSAPS

Keywords provided by Nantes University Hospital:
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

Additional relevant MeSH terms:
Adenoviridae Infections
Melanoma
DNA Virus Infections
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Virus Diseases
Interferon-gamma
Interferons
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014