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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)

Primary Purpose

Metastatic Melanoma

Status
Terminated
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
TIL-Ad-INFg
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Melanoma focused on measuring 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

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU de Nantes

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TIL-Ad-INFg

Arm Description

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Objective response rate
The evaluation of the objective response rate
Tumoral response
The evaluation of the tumoral response of injected lesions every month
Progression-free survival
The evaluation of the progression-free survival,
Overall survival
The evaluation of the overall survival
Immunological response
The evaluation of the immunological response

Full Information

First Posted
March 8, 2010
Last Updated
August 5, 2016
Sponsor
Nantes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01082887
Brief Title
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

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Terminated
Study Start Date
January 2010 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TIL-Ad-INFg
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
TIL-Ad-INFg
Intervention Description
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.
Primary Outcome Measure Information:
Title
Clinical and biological toxicity of combined treatment TIL, IL2 et Ad-INFg
Description
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).
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Objective response rate
Description
The evaluation of the objective response rate
Time Frame
12 months
Title
Tumoral response
Description
The evaluation of the tumoral response of injected lesions every month
Time Frame
12 months
Title
Progression-free survival
Description
The evaluation of the progression-free survival,
Time Frame
12 months
Title
Overall survival
Description
The evaluation of the overall survival
Time Frame
12 months
Title
Immunological response
Description
The evaluation of the immunological response
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brigitte DRENO, Profesor
Organizational Affiliation
Nantes University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gaëlle QUEREUX, Doctor
Organizational Affiliation
Nantes University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Anabelle BROCARD, Doctor
Organizational Affiliation
Nantes University Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
CHU de Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France

12. IPD Sharing Statement

Learn more about this trial

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)

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