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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Transgene Identifier:
First received: June 23, 2011
Last updated: November 3, 2015
Last verified: November 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
Scottsdale, Arizona, United States, 85259
United States, Kansas
Cotton O'Neil Clinical Research Center
Topeka, Kansas, United States, 66606
United States, Kentucky
University of Louisville Hospital
Louisville, Kentucky, United States, 40402
United States, Maryland
Massachusetts General Hospital
Cambridge, Maryland, United States, 2114
Oncology/Hematology P.C.
Rockville, Maryland, United States, 20850
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, North Carolina
Highlands Oncology Group
Fayetteville, North Carolina, United States, 72703
United States, Ohio
Signal Point Clinical Research Center
Middletown, Ohio, United States, 45042
ProMedica Health System Inc
Toledo, Ohio, United States, 43606
United States, Pennsylvania
Abington Hematology Oncology Associates Inc
Willow Grove, Pennsylvania, United States, 19090
United States, Texas
Texas Oncology, P.A. - Abilene (South)
Abilene, Texas, United States, 79606
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75246
ZNA Middelheim
Antwerpen, Belgium, 2020
Clinique Nôtre-Dame de Grâce
Gosselies, Belgium, 6041
Centre Hospitalier de l'Ardenne
Libramont, Belgium, 6800
C. H. U. Sart-Tilman
Liège, Belgium, 4000
CHU, Service de Pneumologie
Besancon, France, 25000
Centre François Baclesse
Caen, France, 14076
CHU de Clermont-Ferrand, Hopital Gabriel Montpied
Clermont-Ferrand, France, 63000
Hôpital Pasteur - Service de médecine F- Pavillon 43
Colmar, France, 68000
Centre Hospitalier Intercommunal de Créteil
Créteil, France, 94010
CHRU de Lille Hopital Calmette
Lille, France, 59037
Clinique François Chénieux
Limoges, France, 87039
Institut Paoli-Calmettes, Service d'oncologie médicale
Marseille, France, 13273
CH Mulhouse Hopital Emile Muller Moenchsberg
Mulhouse, France, 68070
Hopital Saint Joseph
Paris, France, 75014
Hôpital Pontchaillou
Rennes Cedex 09, France, 35033
CHU de Saint-Etienne, Hôpital Nord
Saint Etienne Cedex 02, France, 42055
Institut de Cancérologie Lucien Neuwirth
Saint Priest en Jarez, France, 42270
Centre Médical Alfred Leune
Sainte Feyre, France, 23000
Nouvel Hôpital Civil
Strasbourg, France, 67000
Centre Hospitalier Intercommunal de la Haute Saone
Vesoul cedex, France, 70014
Universitaetsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Universitaetsklinikum Mannheim
Mannheim, Germany, 68167
Orszagos Onkologiai Intezet
Budapest, Hungary, 1122
Semmelweis Egyetem AOK
Budapest, Hungary, 1125
Orszagos Koranyi TBC es Pulmonologiai Intezet
Budapest, Hungary, 1525
Kenezy Korhaz-Rendelointezet Eu Szolgaltato Nonprofit Kft
Debrecen, Hungary, 4032
Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
Gyula, Hungary, 5703
Petz Aladár Megyei Oktató kórház
Győr, Hungary, 9024
Matrai Gyogyintezet
Matrahaza, Hungary, 3233
Tolna Megyei Onkormanyzat Balassa Janos Korhaza
Szekszard, Hungary, 7100
Fejér Megyei Szent György Kórház
Székesfehérvár, Hungary, 8000
Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza
Tatabanya, Hungary, 2800
Tudogyogyintezet Torokbalint
Torokbalint, Hungary, 2045
Zala Megyei Korhaz
Zalaegerszeg, Hungary, 8900
Assaf Harofeh Medical Center
Beer Yaacov, Israel, 70300
Hadassah Ein Kerem Medical Center
Jerusalem, Israel, 91120
Sapir Medical Center Meir Hospital
Kfar-Saba, Israel, 52621
Rabin Medical Center-Beilinson Campus
Petah-Tikva, Israel, 49372
Chaim Sheba Medical Center
Ramat Gan, Israel, 44281
Kaplan Medical Center
Rehovot, Israel, 76100
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel, 64239
IEO Istituto Europeo di Oncologia
Milano, Italy, 20141
Azienda Ospedaliera di Perugia Ospedale S.Maria della Miseri
Perugia, Italy, 6156
A.O.U. Senese Policlinico Santa Maria alle Scotte
Siena, Italy, 53100
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
Lublin, Poland, 20-954
SP Zespol Gruzlicy i Chorob Pluc w Olsztynie
Olsztyn, Poland, 10-357
Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
Otwock, Poland, 05-400
Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
Poznan, Poland, 60569
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
Warszawa, Poland, 02-781
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitario Reina Sofia
Cordoba, Spain, 14004
ICO Girona - Hospital Dr Josep Trueta
Girona, Spain, 17007
Hospital Gregorio Marañon
Madrid, Spain, 28007
START Madrid. Centro Integral Oncologico Clara Campal
Madrid, Spain, 28050
Hospital General Carlos Haya
Malaga, Spain, 29010
Corporació Sanitària Parc Taulí
Sabadell, Spain, 08208
United Kingdom
Queen Elizabeth Hospital
Birmingham, United Kingdom, B15 2TH
Velindre Hospital NHS Trust
Cardiff, United Kingdom, CF14 2TL
Plymouth Oncology Centre
Plymouth, United Kingdom, PL6 8DH
Southampton University Hospitals NHS Trust
Southampton, United Kingdom, SO16 6YD
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: November 3, 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 November 25, 2015