Clinical trial NCT00415818: Immunotherapy With TG4010 in Patients With Advanced Non-Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Lung Cancer
NSCLC
Cancer Vaccine
Stage IV Non-Small Cell Lung Cancer
Stage IIIb Non-Small Cell Lung Cancer with effusion
Lead sponsor: Transgene
Sponsor class: INDUSTRY
First posted: 2006-12-25
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression free survival at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Response Rate according to WHO criteria
timeFrame: 6 months
measure: Time to progression
timeFrame: 6 months
measure: Overall survival
measure: Quality of life
timeFrame: every 6 weeks
Other outcomes:
Locations:
city: Belfort
country: France
facility: Centre Hospitalier Belfort-Montbeliard
city: Besancon
country: France
facility: CHU, Service de Pneumologie
city: Briey
country: France
facility: Centre Hospitalier Général, Service de Pneumologie
city: Caen
country: France
facility: Centre François Baclesse
city: Colmar
country: France
facility: Hôpital Pasteur - Service de médecine F- Pavillon 43
city: Lille
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Institut Paoli-Calmettes, Service d'oncologie médicale
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rennes
country: France
facility: CHRU Hôpital de Pontchaillou
city: Strasbourg
country: France
facility: Hôpital Lyautey - Service de Pneumologie
city: Vesoul
country: France
facility: Centre Hospitalier de la Haute Saône, Service de Pneumologie - Allergologie
city: Gauting
country: Germany
facility: Asklepios Fachkliniken, Zentrum für Pneumonologie
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
city: Köln
country: Germany
facility: Lungenklinik Krankenhaus Merheim
city: Mannheim
country: Germany
facility: Klinikum Mannheim der Ruprecht-Karls
city: Offenburg
country: Germany
facility: Klinikum Offenburg, Medizinische Klinik II
city: Székesfehérvár
country: Hungary
facility: Fejér Megyei Szent György Kórház
city: Bialystok
country: Poland
facility: Oddział II Chorób Płuc i Gruźlicy
city: Bydgoszcz
country: Poland
facility: Kujawsko-Pomorskie Centrum Pulmonologii
city: Krakow
country: Poland
facility: Oddział Chemioterapii
city: Otwock
country: Poland
facility: Oddział III Chorób Płuc i Gruźlicy
city: Poznan
country: Poland
facility: Oddział Onkologii Klinicznej
city: Wrocław
country: Poland
facility: Dolnośląskie Centrum
Study officials:
affiliation: Hôpital Lyautey, Service de Pneumologie
name: Elisabeth QUOIX, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.