Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer (TIME)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Transgene
Information provided by (Responsible Party):
Transgene Identifier:
First received: June 23, 2011
Last updated: March 18, 2015
Last verified: March 2015

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.

Condition Intervention Phase
Non-Small-Cell Lung Carcinoma
Biological: TG4010
Drug: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIB/III Randomized, Double-blind, Placebo Controlled Study Comparing First Line Therapy With or Without TG4010 Immunotherapy Product in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:

Further study details as provided by Transgene:

Primary Outcome Measures:
  • Phase 2: Progression-free Survival (PFS) [ Time Frame: Approximately 15 months ] [ Designated as safety issue: No ]
    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.

  • Phase 3: Overall Survival (OS) [ Time Frame: Approximately 27 months ] [ Designated as safety issue: No ]
    OS is measured from date of randomization to date of death from any cause.

Secondary Outcome Measures:
  • Phase 2 : Overall Survival (OS) [ Time Frame: Approximately 15 months ] [ Designated as safety issue: No ]
  • Phase 2 : Overall Response Rate (ORR) [ Time Frame: Approximately 15 months ] [ Designated as safety issue: No ]
  • Phase 3: Progression-free Survival (PFS) [ Time Frame: Approximately 27 months ] [ Designated as safety issue: No ]
  • Phase 3 : Overall Response Rate (ORR) [ Time Frame: Approximately 27 months ] [ Designated as safety issue: No ]
  • Phase 2 : Duration of response [ Time Frame: Approximately 15 months ] [ Designated as safety issue: No ]
  • Phase 2: Safety [ Time Frame: Approximately 15 months ] [ Designated as safety issue: Yes ]
  • Phase 3: Duration of response [ Time Frame: Approximately 27 months ] [ Designated as safety issue: No ]
  • Phase 3: Safety [ Time Frame: Approximately 27 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1000
Study Start Date: April 2012
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 - TG4010 + first line therapy
First-line therapy and maintenance therapy
Biological: TG4010

TG4010 • TG4010 will be administered starting on Day 1 (D1) of Cycle 1 of chemotherapy and will be administered weekly for 6 weeks by subcutaneous (SC) injections and then once every 3 weeks until progression or discontinuation due to any reason.

Chemotherapy (and bevacizumab if prescribed), will be given as 21-day cycles for a minimum of 4 cycles and up to 6 cycles.

First line therapy:

  • Non-squamous carcinoma: pemetrexed + cisplatin or paclitaxel + carboplatin +/- bevacizumab
  • Squamous carcinoma: gemcitabine + cisplatin or paclitaxel + carboplatin

Maintenance therapy:

• Pemetrexed or erlotinib for eligible patients and according to labeling.

Active Comparator: Arm 2 : Placebo + first line therapy
First-line therapy and maintenance therapy
Drug: placebo

Placebo will be administered starting on D1 of Cycle 1 of chemotherapy and will be administered weekly for 6 weeks by SC injections and then once every 3 weeks until progression or discontinuation due to any reason.

  • First line therapy: as in Arm 1
  • Maintenance therapy: as in Arm 1
Other Names:
  • paclitaxel
  • carboplatin
  • pemetrexed
  • cisplatin
  • gemcitabine
  • bevacizumab (if prescribed)
  • erlotinib


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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
  • 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)
    • 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)
    • 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)

Exclusion Criteria:

  • 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
  • Patient with an organ allograft
  • Known allergy to eggs, gentamicin or platinum-containing compounds
  • 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
  • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01383148

  Hide Study Locations
United States, Arizona
Mayo Clinic Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Elen Ross    480-301-8000      
United States, Kansas
Cotton O'Neil Clinical Research Center Recruiting
Topeka, Kansas, United States, 66606
Contact: David Einspahr   
Principal Investigator: David Einspahr         
United States, Kentucky
University of Louisville Hospital Recruiting
Louisville, Kentucky, United States, 40402
Contact: Goetz Kloecker   
Principal Investigator: Goetz Kloecker         
United States, Maryland
Massachusetts General Hospital Recruiting
Cambridge, Maryland, United States, 2114
Contact: Lecia Sequist   
Principal Investigator: Lecia Sequist         
Oncology/Hematology P.C. Recruiting
Rockville, Maryland, United States, 20850
Contact: Paul Thambi   
Principal Investigator: Paul Thambi         
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Saiama Waqar   
Principal Investigator: Saiama Waqar         
United States, North Carolina
Highlands Oncology Group Recruiting
Fayetteville, North Carolina, United States, 72703
Contact: Joseph Beck   
Principal Investigator: Joseph Beck         
United States, Ohio
Signal Point Clinical Research Center Recruiting
Middletown, Ohio, United States, 45042
Contact: Nandagopal Vrindavanam   
Principal Investigator: Nandagopal Vrindavanam         
ProMedica Health System Inc Not yet recruiting
Toledo, Ohio, United States, 43606
Contact: William Horvath   
Principal Investigator: William Horvath         
United States, Pennsylvania
Abington Hematology Oncology Associates Inc Recruiting
Willow Grove, Pennsylvania, United States, 19090
Contact: Joseph Potz   
Principal Investigator: Joseph Potz         
United States, Texas
Texas Oncology, P.A. - Abilene (South) Recruiting
Abilene, Texas, United States, 79606
Contact: Anton Melnyk   
Principal Investigator: Anton Melnyk         
Mary Crowley Medical Research Center Recruiting
Dallas, Texas, United States, 75246
Contact: John Nemunaitis   
Principal Investigator: John Nemunaitis         
ZNA Middelheim Recruiting
Antwerpen, Belgium, 2020
Contact: Daniella Galdermans   
Principal Investigator: Daniella Galdermans         
Clinique Nôtre-Dame de Grâce Recruiting
Gosselies, Belgium, 6041
Contact: Kim Vanderheyde   
Principal Investigator: Kim Vanderheyde         
Centre Hospitalier de l'Ardenne Recruiting
Libramont, Belgium, 6800
Contact: Frederic Forget   
Principal Investigator: Frederic Forget         
C. H. U. Sart-Tilman Recruiting
Liège, Belgium, 4000
Contact: Anne Sibille, Dr   
Principal Investigator: Anne Sibille, Dr         
CHU, Service de Pneumologie Recruiting
Besancon, France, 25000
Contact: Virginie WESTEEL, M.D.    +33(0)3 81 66 88 12   
Principal Investigator: Virginie WESTEEL, M.D.         
Centre François Baclesse Recruiting
Caen, France, 14076
Contact: Radj Gervais, M.D.    +33(0)2 31 45 50 13   
Principal Investigator: Radj Gervais, M.D.         
CHU de Clermont-Ferrand, Hopital Gabriel Montpied Recruiting
Clermont-Ferrand, France, 63000
Contact: Patrick Merle   
Principal Investigator: Patrick Merle         
Hôpital Pasteur - Service de médecine F- Pavillon 43 Recruiting
Colmar, France, 68000
Contact: Jean-Philippe OSTER, M.D.    +33(0)3 89 12 48 14   
Principal Investigator: Jean-Philippe OSTER, M.D.         
Centre Hospitalier Intercommunal de Créteil Recruiting
Créteil, France, 94010
Contact: Christos Chouaid   
Principal Investigator: Christos Chouaid         
CHRU de Lille Hopital Calmette Recruiting
Lille, France, 59037
Contact: Arnaud Scherpereel   
Principal Investigator: Arnaud Scherpereel         
Clinique François Chénieux Recruiting
Limoges, France, 87039
Contact: Dominique Genet   
Principal Investigator: Dominique Genet         
Institut Paoli-Calmettes, Service d'oncologie médicale Recruiting
Marseille, France, 13273
Contact: Anne MADROSZYK, M.D.    +33 (0)   
Principal Investigator: Anne MADROSZYK, M.D.         
CH Mulhouse Hopital Emile Muller Moenchsberg Recruiting
Mulhouse, France, 68070
Contact: Didier Debieuvre   
Principal Investigator: Didier : Debieuvre         
Hopital Saint Joseph Not yet recruiting
Paris, France, 75014
Contact: Jean Trédaniel   
Principal Investigator: Jean Trédaniel         
Hôpital Pontchaillou Recruiting
Rennes Cedex 09, France, 35033
Contact: Herve Lena   
Principal Investigator: Herve Lena         
CHU de Saint-Etienne, Hôpital Nord Not yet recruiting
Saint Etienne Cedex 02, France, 42055
Contact: Jean-Michel Vergnon   
Principal Investigator: Jean-Michel Vergnon         
Institut de Cancérologie Lucien Neuwirth Recruiting
Saint Priest en Jarez, France, 42270
Contact: Pierre Fournel   
Principal Investigator: Pierre Fournel         
Centre Médical Alfred Leune Recruiting
Sainte Feyre, France, 23000
Contact: Philippe Slaouti   
Principal Investigator: Philippe Slaouti         
Nouvel Hôpital Civil Recruiting
Strasbourg, France, 67000
Contact: QUOIX Elisabeth, Prof    + (33).(0)      
Principal Investigator: QUOIX Elisabeth, Prof         
Centre Hospitalier Intercommunal de la Haute Saone Recruiting
Vesoul cedex, France, 70014
Contact: Jean-Pierre Gury   
Principal Investigator: Jean-Pierre Gury         
Universitaetsklinikum Hamburg-Eppendorf Recruiting
Hamburg, Germany, 20246
Contact: Djordje Atanackovic    40741055032   
Principal Investigator: Djordje Atanackovic         
Universitaetsklinikum Mannheim Not yet recruiting
Mannheim, Germany, 68167
Contact: Christian Manegold    496213830   
Principal Investigator: Christian Manegold         
Orszagos Koranyi TBC es Pulmonologiai Intezet Recruiting
Budapest, Hungary, 1525
Contact: Erzsebet Juhasz   
Principal Investigator: Erzsebet Juhasz         
Orszagos Onkologiai Intezet Not yet recruiting
Budapest, Hungary, 1122
Contact: Istvan Lang   
Principal Investigator: Istvan Lang         
Semmelweis Egyetem AOK Recruiting
Budapest, Hungary, 1125
Contact: Gyorgy Losonczy   
Principal Investigator: Gyorgy Losonczy         
Kenezy Korhaz-Rendelointezet Eu Szolgaltato Nonprofit Kft Not yet recruiting
Debrecen, Hungary, 4032
Contact: Istvan Varkonyi   
Principal Investigator: Istvan Varkonyi         
Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza Recruiting
Gyula, Hungary, 5703
Contact: Zsuzsanna Sztancsik   
Principal Investigator: Zsuzsanna Sztancsik         
Petz Aladár Megyei Oktató kórház Recruiting
Győr, Hungary, 9024
Contact: Gabriella Herodek, M.D.    +36 96 418244   
Principal Investigator: Gabriella Herodek         
Matrai Gyogyintezet Not yet recruiting
Matrahaza, Hungary, 3233
Contact: Laszlo Urban   
Principal Investigator: Laszlo Urban         
Tolna Megyei Onkormanyzat Balassa Janos Korhaza Recruiting
Szekszard, Hungary, 7100
Contact: Yousuf Al-Farhat   
Principal Investigator: Yousuf Al-Farhat         
Fejér Megyei Szent György Kórház Recruiting
Székesfehérvár, Hungary, 8000
Contact: Zsolt PAPAI, M.D.    +36 22 535700      
Principal Investigator: Zsolt PAPAI, M.D.         
Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza Recruiting
Tatabanya, Hungary, 2800
Contact: Csaba Bocskei   
Principal Investigator: Csaba Bocskei         
Tudogyogyintezet Torokbalint Recruiting
Torokbalint, Hungary, 2045
Contact: Zsuzsanna Mark   
Principal Investigator: Zsuzsanna Mark         
Zala Megyei Korhaz Recruiting
Zalaegerszeg, Hungary, 8900
Contact: Sandor Tehenes   
Principal Investigator: Sandor Tehenes         
Assaf Harofeh Medical Center Recruiting
Beer Yaacov, Israel, 70300
Contact: Arnold Cyjon   
Principal Investigator: Arnold Cyjon         
Hadassah Ein Kerem Medical Center Recruiting
Jerusalem, Israel, 91120
Contact: Hovav Nechushtan   
Principal Investigator: Hovav Nechushtan         
Sapir Medical Center Meir Hospital Recruiting
Kfar-Saba, Israel, 52621
Contact: Maya Gottfried   
Principal Investigator: Maya Gottfried         
Rabin Medical Center-Beilinson Campus Recruiting
Petah-Tikva, Israel, 49372
Contact: Salomon Stemmer   
Principal Investigator: Salomon Stemmer         
Chaim Sheba Medical Center Recruiting
Ramat Gan, Israel, 44281
Contact: Amir Onn   
Principal Investigator: Amir Onn         
Kaplan Medical Center Recruiting
Rehovot, Israel, 76100
Contact: Rivka Katsnelson   
Principal Investigator: Rivka Katsnelson         
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 64239
Contact: Ofer Merimsky   
Principal Investigator: Ofer Merimsky         
IEO Istituto Europeo di Oncologia Recruiting
Milano, Italy, 20141
Contact: Marinis Felippo, Dr   
Principal Investigator: Marinis Felippo, Dr         
Azienda Ospedaliera di Perugia Ospedale S.Maria della Miseri Recruiting
Perugia, Italy, 6156
Contact: Lucio Crinò   
Principal Investigator: Lucio Crinò         
A.O.U. Senese Policlinico Santa Maria alle Scotte Recruiting
Siena, Italy, 53100
Contact: Michele Maio   
Principal Investigator: Michele Maio         
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie Not yet recruiting
Lublin, Poland, 20-954
Contact: Janusz Milanowski   
Principal Investigator: Janusz Milanowski         
SP Zespol Gruzlicy i Chorob Pluc w Olsztynie Recruiting
Olsztyn, Poland, 10-357
Contact: Andrzej Kazarnowicz   
Principal Investigator: Andrzej Kazarnowicz         
Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy Recruiting
Otwock, Poland, 05-400
Contact: Aleksandra Szczesna   
Principal Investigator: Aleksandra Szczesna         
Przychodnia Med-Polonia Sp. z o.o. Recruiting
Poznan, Poland, 60693
Contact: Rodryg Ramlau    48616643330   
Principal Investigator: Rodryg Ramlau         
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie Recruiting
Warszawa, Poland, 02-781
Contact: Piotr Jaskiewicz   
Principal Investigator: Piotr Jaskiewicz         
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Enriqueta Felip Font   
Principal Investigator: Enriqueta Felip Font         
Hospital Universitario Reina Sofia Recruiting
Cordoba, Spain, 14004
Contact: Isidoro Carlos Barneto Aranda   
Principal Investigator: Isidoro Carlos Barneto Aranda         
ICO Girona - Hospital Dr Josep Trueta Recruiting
Girona, Spain, 17007
Contact: Rut Porta Balany   
Principal Investigator: Rut Porta Balany         
Hospital Gregorio Marañon Recruiting
Madrid, Spain, 28007
Contact: Rosa Álvarez   
Principal Investigator: Rosa Álvarez         
START Madrid. Centro Integral Oncologico Clara Campal Recruiting
Madrid, Spain, 28050
Contact: Cristobal Belda   
Principal Investigator: Cristobal Belda         
Hospital General Carlos Haya Recruiting
Malaga, Spain, 29010
Contact: Manuel Cobo Dols   
Principal Investigator: Manuel Cobo Dols         
Corporació Sanitària Parc Taulí Recruiting
Sabadell, Spain, 08208
Contact: Yolanda Garcia   
Principal Investigator: Yolanda Garcia         
United Kingdom
Queen Elizabeth Hospital Recruiting
Birmingham, United Kingdom, B15 2TH
Contact: Gary Middleton   
Principal Investigator: Gary Middleton         
Velindre Hospital NHS Trust Recruiting
Cardiff, United Kingdom, CF14 2TL
Contact: Jason Lester   
Principal Investigator: Jason Lester         
Plymouth Oncology Centre Recruiting
Plymouth, United Kingdom, PL6 8DH
Contact: Pantelakis Yiannakis   
Principal Investigator: Pantelakis Yiannakis         
Southampton University Hospitals NHS Trust Recruiting
Southampton, United Kingdom, SO16 6YD
Contact: Christian Ottensmeier   
Principal Investigator: Christian Ottensmeier         
Sponsors and Collaborators
Principal Investigator: QUOIX Elisabeth, Prof Hôpitaux Universitaires de Strasbourg
  More Information

Additional Information:
NSCLC  This link exits the site

No publications provided

Responsible Party: Transgene Identifier: NCT01383148     History of Changes
Other Study ID Numbers: TG4010.14/TIME, 8559
Study First Received: June 23, 2011
Last Updated: March 18, 2015
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration

Keywords provided by Transgene:

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses processed this record on October 07, 2015