Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer
- Conditions
- Non-Small-Cell Lung Carcinoma
- Interventions
- Biological: TG4010Drug: placebo
- Registration Number
- NCT01383148
- Lead Sponsor
- Transgene
- Brief Summary
This is a Phase IIb/III randomized, double-blind, placebo-controlled study to compare the efficacy and safety of first-line therapy combined with TG4010 or placebo in stage IV non-small cell lung cancer (NSCLC).
TG4010 is a suspension of recombinant Modified Vaccinia virus strain Ankara (MVA strain) carrying coding sequences for human MUC1 antigen and human interleukin-2 (IL2). TG4010 has been developed for use as an immunotherapy in cancer patients whose tumors express the MUC1 antigen.
TG4010 is intended to induce a MUC1-specific cellular immune response and to produce a non-specific activation of several components of the immune system.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 222
-
Histologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, undifferentiated carcinoma or other)
-
Stage IV cancer according to TNM classification (7th edition - UICC, December 2009; includes tumor with malignant pleural or pericardial effusion
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Tumor biopsy specimen with ≥ 50% of MUC1 expressing tumor cells determined by Immunohistochemistry (IHC) staining on fixed pathological material. Biopsy may come either from the primary tumor or from a metastasis. Cytological material is not accepted for this analysis
-
Patient's naïve to first-line therapy for the advanced stage of the disease. Previous neoadjuvant or adjuvant therapy is allowed for patients who successfully underwent complete radical surgery and if last treatment was administered more than 12 months prior to the start of the study treatment, i.e., D1 of Cycle 1.
-
At least one measurable lesion by CT scan or MRI based on RECIST version 1.1
-
PS 0 or 1 on the ECOG scale
-
Adequate hematological, hepatic, and renal function:
-
Hemoglobin ≥ 10.0 g/dL
-
White Blood Cells (WBC) ≥ 3.0x10E9/L including
- Neutrophils ≥ 1.5x109/L
- Total lymphocytes count ≥ 0.5x10E9/L
-
Platelets count ≥ 100x10E9/L
-
Serum alkaline phosphatase ≤ 3x ULN (upper limit of normal)in the absence of liver or bone metastases or ≤5 ULN(in patients with documented bone or liver metastases)
-
Serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) ≤ 2.5 x ULN in the absence of liver metastases or =< 5 ULN in case of liver metastases)
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Total bilirubin ≤1.5 x ULN
-
Glomerular Filtration Rate ≥ 60 mL/min (according to Modification of the Diet in Renal Disease (MDRD) formula or cockroft & Gault formula)
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Serum albumin ≥ 30 g/L
-
Effective contraception during the study period and for 3 months after the last study treatment administration (male and female patient)
-
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Patients having Central Nervous System (CNS) metastases. Patients who have had brain metastases surgically removed or irradiated with no residual disease confirmed by imaging are allowed
-
Documented EGFR activating mutations (if already tested)
-
Prior history of other malignancy except:
- Basal cell carcinoma of the skin
- Cervical intra epithelial neoplasia
- Other cancer curatively treated with no evidence of disease for at least 5 years
-
Patients under chronic treatment with systemic corticoids or other immunosuppressive drugs (e.g., cyclosporine) for a period of at least 4 weeks and whose treatment was not stopped 1 week prior to the start of the study treatment (i.e., D1 of Cycle 1)
-
Positive serology for Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV); presence in the serum of the antigens HBs
-
Patient with any underlying medical condition that the treating physician considers might be aggravated by treatment or which is not controlled (e.g., elevated troponin or creatinine, uncontrolled diabetes)
-
Patient with major surgery or radiotherapy within 4 weeks prior to the start of the study treatment (i.e., D1 of Cycle 1). Prior surgery or radiation therapy aimed at local palliation or attempted local disease control is permitted
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Patient with an organ allograft
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Known allergy to eggs, gentamicin or platinum-containing compounds
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Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment (i.e., D1 of Cycle 1)
-
Patient unable or unwilling to comply with the protocol requirements
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Pregnancy or lactation
-
Bevacizumab will be allowed for patients with non-squamous carcinoma. Prescribing information must be followed and precautions have to be taken into consideration (e.g., patients having presented a serious hemorrhage or recent hemoptysis should not receive bevacizumab).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 - TG4010 + first line therapy TG4010 First-line therapy and maintenance therapy Arm 2 : Placebo + first line therapy placebo First-line therapy and maintenance therapy
- Primary Outcome Measures
Name Time Method Phase 3: Overall Survival (OS) Approximately 27 months OS is measured from date of randomization to date of death from any cause.
Phase 2: Progression-free Survival (PFS) Approximately 15 months PFS is measured from date of randomization to radiographically documented progression according to RECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.
- Secondary Outcome Measures
Name Time Method Phase 2 : Overall Survival (OS) Approximately 15 months Phase 2 : Overall Response Rate (ORR) Approximately 15 months Phase 3: Progression-free Survival (PFS) Approximately 27 months Phase 2: Safety Approximately 15 months Phase 3: Duration of response Approximately 27 months Phase 3 : Overall Response Rate (ORR) Approximately 27 months Phase 3: Safety Approximately 27 months Phase 2 : Duration of response Approximately 15 months
Trial Locations
- Locations (72)
Universitaetsklinikum Mannheim
🇩🇪Mannheim, Germany
Orszagos Koranyi TBC es Pulmonologiai Intezet
🇭🇺Budapest, Hungary
Petz Aladár Megyei Oktató kórház
🇭🇺Győr, Hungary
Fejér Megyei Szent György Kórház
🇭🇺Székesfehérvár, Hungary
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Velindre Hospital NHS Trust
🇬🇧Cardiff, United Kingdom
Southampton University Hospitals NHS Trust
🇬🇧Southampton, United Kingdom
Corporació Sanitària Parc Taulí
🇪🇸Sabadell, Spain
Plymouth Oncology Centre
🇬🇧Plymouth, United Kingdom
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Hospital General Carlos Haya
🇪🇸Malaga, Spain
Hospital Gregorio Marañon
🇪🇸Madrid, Spain
Cotton O'Neil Clinical Research Center
🇺🇸Topeka, Kansas, United States
University of Louisville Hospital
🇺🇸Louisville, Kentucky, United States
Mayo Clinic Arizona
🇺🇸Scottsdale, Arizona, United States
Washington University
🇺🇸St. Louis, Missouri, United States
Massachusetts General Hospital
🇺🇸Cambridge, Maryland, United States
Oncology/Hematology P.C.
🇺🇸Rockville, Maryland, United States
Highlands Oncology Group
🇺🇸Fayetteville, North Carolina, United States
ProMedica Health System Inc
🇺🇸Toledo, Ohio, United States
Signal Point Clinical Research Center
🇺🇸Middletown, Ohio, United States
Abington Hematology Oncology Associates Inc
🇺🇸Willow Grove, Pennsylvania, United States
Texas Oncology, P.A. - Abilene (South)
🇺🇸Abilene, Texas, United States
Mary Crowley Medical Research Center
🇺🇸Dallas, Texas, United States
ZNA Middelheim
🇧🇪Antwerpen, Belgium
Clinique Nôtre-Dame de Grâce
🇧🇪Gosselies, Belgium
Centre Hospitalier de l'Ardenne
🇧🇪Libramont, Belgium
C. H. U. Sart-Tilman
🇧🇪Liège, Belgium
CHU, Service de Pneumologie
🇫🇷Besancon, France
Centre François Baclesse
🇫🇷Caen, France
CHU de Clermont-Ferrand, Hopital Gabriel Montpied
🇫🇷Clermont-Ferrand, France
Hôpital Pasteur - Service de médecine F- Pavillon 43
🇫🇷Colmar, France
Centre Hospitalier Intercommunal de Créteil
🇫🇷Créteil, France
CHRU de Lille Hopital Calmette
🇫🇷Lille, France
Clinique François Chénieux
🇫🇷Limoges, France
Institut Paoli-Calmettes, Service d'oncologie médicale
🇫🇷Marseille, France
CH Mulhouse Hopital Emile Muller Moenchsberg
🇫🇷Mulhouse, France
Hôpital Pontchaillou
🇫🇷Rennes Cedex 09, France
Institut de Cancérologie Lucien Neuwirth
🇫🇷Saint Priest en Jarez, France
Hopital Saint Joseph
🇫🇷Paris, France
CHU de Saint-Etienne, Hôpital Nord
🇫🇷Saint Etienne Cedex 02, France
Nouvel Hôpital Civil
🇫🇷Strasbourg, France
Centre Médical Alfred Leune
🇫🇷Sainte Feyre, France
Centre Hospitalier Intercommunal de la Haute Saone
🇫🇷Vesoul cedex, France
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
Semmelweis Egyetem AOK
🇭🇺Budapest, Hungary
Kenezy Korhaz-Rendelointezet Eu Szolgaltato Nonprofit Kft
🇭🇺Debrecen, Hungary
Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
🇭🇺Gyula, Hungary
Tolna Megyei Onkormanyzat Balassa Janos Korhaza
🇭🇺Szekszard, Hungary
Matrai Gyogyintezet
🇭🇺Matrahaza, Hungary
Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza
🇭🇺Tatabanya, Hungary
Tudogyogyintezet Torokbalint
🇭🇺Torokbalint, Hungary
Zala Megyei Korhaz
🇭🇺Zalaegerszeg, Hungary
Sapir Medical Center Meir Hospital
🇮🇱Kfar-Saba, Israel
Assaf Harofeh Medical Center
🇮🇱Beer Yaacov, Israel
Hadassah Ein Kerem Medical Center
🇮🇱Jerusalem, Israel
Chaim Sheba Medical Center
🇮🇱Ramat Gan, Israel
Rabin Medical Center-Beilinson Campus
🇮🇱Petah-Tikva, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
IEO Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Azienda Ospedaliera di Perugia Ospedale S.Maria della Miseri
🇮🇹Perugia, Italy
A.O.U. Senese Policlinico Santa Maria alle Scotte
🇮🇹Siena, Italy
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
🇵🇱Lublin, Poland
Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
🇵🇱Otwock, Poland
SP Zespol Gruzlicy i Chorob Pluc w Olsztynie
🇵🇱Olsztyn, Poland
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
🇵🇱Poznan, Poland
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
🇵🇱Warszawa, Poland
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
ICO Girona - Hospital Dr Josep Trueta
🇪🇸Girona, Spain
START Madrid. Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain