Immunotherapy With TG4010 in Patients With Advanced Non-Small Cell Lung Cancer

NCT ID: NCT00415818

Last Updated: 2014-07-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2010-03-31

Brief Summary

The primary Objective is to assess the efficacy of TG4010 combined to chemotherapy in comparison with chemotherapy alone in patients with advanced non small cell lung cancer.

Detailed Description

In the experimental arm patients receive subcutaneous injections of TG4010 at the dose of 108 pfu in combination with chemotherapy treatment whereas patients in the control arm receive chemotherapy alone. The chemotherapy associates cisplatin and gemcitabine and is given for up to 6 cycles or progressive disease, whichever occurs first.

TG4010 is administered once per week for 6 weeks, then once every 3 weeks in combination with chemotherapy and thereafter as monotherapy until documentation of progressive disease.

Tumor response will be evaluated every 6 weeks by a CT-scan and results will be available before starting an additional treatment period of 6 weeks. The tumor response taken into account will be for each patient the best overall response obtained during the study.

The endpoint of the study is based on Progression Free Survival (PFS) at 6 months.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

MVA-MUC1-IL2 in combination with 1st line Chemotherapy

Group Type: EXPERIMENTAL

MVA-MUC1-IL2

Intervention Type: BIOLOGICAL

MVA-MUC1-IL2:

Dose of 10exp8 plaque forming units (pfu).

Chemotherapy:

Arm 1 and Arm 2 Intravenous CT: cisplatin (75mg/m² at Day 1) and gemcitabine (1250mg/m² at Days 1 and 8) every 3 weeks, for up to six cycles or until progressive disease, whichever occurred first.

1st line Chemotherapy

Intervention Type: DRUG

Arm 2

1st line Chemotherapy without a MVA-MUC1-IL2 combination

Group Type: ACTIVE_COMPARATOR

1st line Chemotherapy

Intervention Type: DRUG

Interventions

MVA-MUC1-IL2

MVA-MUC1-IL2:

Dose of 10exp8 plaque forming units (pfu).

Chemotherapy:

Arm 1 and Arm 2 Intravenous CT: cisplatin (75mg/m² at Day 1) and gemcitabine (1250mg/m² at Days 1 and 8) every 3 weeks, for up to six cycles or until progressive disease, whichever occurred first.

Intervention Type: BIOLOGICAL

1st line Chemotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed non-small cell carcinoma of the lung (adenocarcinoma, squamous cell carcinoma, or large cell carcinoma);
• Histological documentation of MUC1 antigen expression on the primary tumor or on metastasis, as defined by a positive staining by immuno-histo-chemistry in at least 25% of the tumor cells in the conditions described in the technical documentation of the monoclonal antibody;
• Patients will have stage IIIb "wet" (with pleural or pericardial effusion) or IV disease, with no prior systemic therapy for advanced disease except for adjuvant treatment. Prior surgery or radiation therapy aimed at local palliation or attempted local disease control is permitted;
• At least one measurable lesion by Computed Tomography (CT-scanner) according to WHO criteria (lesion accurately measured in two dimensions with longest diameter equal or greater to 10 mm with spiral CT scan);
• Adequate hematological, hepatic, and renal function:

• Hemoglobin >= 10.0 g/dL; WBC >= 3.0x10e9/L including neutrophils >= 1.5x10e9/L and total lymphocytes count >= 0.5x10e9/L; platelets count >= 100x10e9/L;
• Bilirubin =< 2x the upper limit of normal and serum transaminases =< 3x the upper limit of normal;
• Glomerular Filtration Rate higher than 60 ml/mn according to Cockcroft formula;
• Performance status 0 or 1 on the ECOG scale (Appendix 2);
• Minimum estimated life expectancy of 4 months;
• Written informed consent from patient.

Exclusion Criteria

• Concomitant brain metastases. If previous brain metastases were treated, the absence of evolution is to be demonstrated by the MRI or scanner performed at baseline;
• Prior history of other malignancy except basal cell carcinoma and intra-epithelial cervical cancer or other cancer with complete response since at least 5 years;
• History of any form of systemic therapy for advanced non-small cell cancer of the lung except for (neo)adjuvant treatment;
• Previous (within 4 weeks prior to day 1) or concomitant long term treatment with systemic steroids, immunosuppressive / immunomodulating drugs (e.g. Cyclosporine, corticoïds);
• Positive serology for HIV or HCV; positive antigens for hepatitis B;
• Serious concomitant medical disorder;
• Major surgery within 4 weeks prior to day 1;
• Patient with an organ allograft;
• Allergy to eggs;
• Participation in another experimental protocol during the study period, or within 4 weeks prior to day 1;
• Pregnancy at the entry or women who are breast feeding;
• Patient without adequate protection against pregnancy during the conduct of the study and for 3 months after the last injection of TG4010 and/or chemotherapy;
• History of substance abuse;
• Patient unable or unwilling to comply with the protocol requirements.

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

Sponsors

Transgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elisabeth QUOIX, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hôpital Lyautey, Service de Pneumologie

Locations

Centre Hospitalier Belfort-Montbeliard

Belfort, , France

CHU, Service de Pneumologie

Besançon, , France

Centre Hospitalier Général, Service de Pneumologie

Briey, , France

Centre François Baclesse

Caen, , France

Hôpital Pasteur - Service de médecine F- Pavillon 43

Colmar, , France

Centre Oscar Lambret

Lille, , France

Institut Paoli-Calmettes, Service d'oncologie médicale

Marseille, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

CHRU Hôpital de Pontchaillou

Rennes, , France

Hôpital Lyautey - Service de Pneumologie

Strasbourg, , France

Centre Hospitalier de la Haute Saône, Service de Pneumologie - Allergologie

Vesoul, , France

Lungenklinik Krankenhaus Merheim

Cologne, , Germany

Asklepios Fachkliniken, Zentrum für Pneumonologie

Gauting, , Germany

Thoraxklinik Heidelberg

Heidelberg, , Germany

Klinikum Mannheim der Ruprecht-Karls

Mannheim, , Germany

Klinikum Offenburg, Medizinische Klinik II

Offenburg, , Germany

Fejér Megyei Szent György Kórház

Székesfehérvár, , Hungary

Oddział II Chorób Płuc i Gruźlicy

Bialystok, , Poland

Kujawsko-Pomorskie Centrum Pulmonologii

Bydgoszcz, , Poland

Oddział Chemioterapii

Krakow, , Poland

Oddział III Chorób Płuc i Gruźlicy

Otwock, , Poland

Oddział Onkologii Klinicznej

Poznan, , Poland

Dolnośląskie Centrum

Wroclaw, , Poland

Countries

France; Germany; Hungary; Poland

References

Quoix E, Ramlau R, Westeel V, Papai Z, Madroszyk A, Riviere A, Koralewski P, Breton JL, Stoelben E, Braun D, Debieuvre D, Lena H, Buyse M, Chenard MP, Acres B, Lacoste G, Bastien B, Tavernaro A, Bizouarne N, Bonnefoy JY, Limacher JM. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial. Lancet Oncol. 2011 Nov;12(12):1125-33. doi: 10.1016/S1470-2045(11)70259-5. Epub 2011 Oct 21.

Reference Type: RESULT

PMID: 22019520 (View on PubMed)

Related Links

http://www.nlm.nih.gov/medlineplus/lungcancer.html

Related Info

Other Identifiers

TG4010.09

Identifier Type: -

Identifier Source: org_study_id