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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

A Phase IIb Multicentric Controlled Study Evaluating the Therapeutic Vaccine TG4010(MVA-MUC1-IL2) as an Adjunct to Standard Chemotherapy in Advanced Non Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00415818
• Other study ID #: TG4010.09
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: December 22, 2006
• Last updated: July 15, 2014
• Start date: December 2005
• Est. completion date: March 2010

Study information

• Verified date: July 2014
• Source: Transgene
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationPoland: Ministry of HealthHungary: National Institute of PharmacyGermany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Biological:
• 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.

Drug:
• 1st line Chemotherapy

Locations

Country	Name	City	State
France	Centre Hospitalier Belfort-Montbeliard	Belfort
France	CHU, Service de Pneumologie	Besancon
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
Germany	Asklepios Fachkliniken, Zentrum für Pneumonologie	Gauting
Germany	Thoraxklinik Heidelberg	Heidelberg
Germany	Lungenklinik Krankenhaus Merheim	Köln
Germany	Klinikum Mannheim der Ruprecht-Karls	Mannheim
Germany	Klinikum Offenburg, Medizinische Klinik II	Offenburg
Hungary	Fejér Megyei Szent György Kórház	Székesfehérvár
Poland	Oddzial II Chorób Pluc i Gruzlicy	Bialystok
Poland	Kujawsko-Pomorskie Centrum Pulmonologii	Bydgoszcz
Poland	Oddzial Chemioterapii	Krakow
Poland	Oddzial III Chorób Pluc i Gruzlicy	Otwock
Poland	Oddzial Onkologii Klinicznej	Poznan
Poland	Dolnoslaskie Centrum	Wroclaw

Sponsors (1)

Lead Sponsor	Collaborator
Transgene

Countries where clinical trial is conducted

France,  Germany,  Hungary,  Poland, 

References & Publications (1)

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 vaccinati — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival at 6 months		6 months	No
Secondary	Response Rate according to WHO criteria		6 months	No
Secondary	Time to progression		6 months	No
Secondary	Overall survival			Yes
Secondary	Quality of life		every 6 weeks	No

External Links

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