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

January 4, 2017 updated by: Transgene

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)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

222

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerpen, Belgium, 2020
        • ZNA Middelheim
      • Gosselies, Belgium, 6041
        • Clinique Notre-Dame de Grâce
      • Libramont, Belgium, 6800
        • Centre Hospitalier de l'Ardenne
      • Liège, Belgium, 4000
        • C. H. U. Sart-Tilman
  • France
      • Besancon, France, 25000
        • CHU, Service de Pneumologie
      • Caen, France, 14076
        • Centre François Baclesse
      • Clermont-Ferrand, France, 63000
        • CHU de Clermont-Ferrand, Hôpital Gabriel Montpied
      • Colmar, France, 68000
        • Hôpital Pasteur - Service de médecine F- Pavillon 43
      • Créteil, France, 94010
        • Centre hospitalier intercommunal de Créteil
      • Lille, France, 59037
        • CHRU de Lille Hopital Calmette
      • Limoges, France, 87039
        • Clinique Francois Chenieux
      • Marseille, France, 13273
        • Institut Paoli-Calmettes, Service d'oncologie médicale
      • Mulhouse, France, 68070
        • CH Mulhouse Hopital Emile Muller Moenchsberg
      • Paris, France, 75014
        • Hôpital Saint Joseph
      • Rennes Cedex 09, France, 35033
        • Hôpital Pontchaillou
      • Saint Etienne Cedex 02, France, 42055
        • CHU de Saint-Etienne, Hopital Nord
      • Saint Priest en Jarez, France, 42270
        • Institut de Cancérologie Lucien Neuwirth
      • Sainte Feyre, France, 23000
        • Centre Médical Alfred Leune
      • Strasbourg, France, 67000
        • Nouvel Hopital Civil
      • Vesoul cedex, France, 70014
        • Centre Hospitalier Intercommunal de la Haute Saône
  • Germany
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf
      • Mannheim, Germany, 68167
        • Universitaetsklinikum Mannheim
  • Hungary
      • Budapest, Hungary, 1122
        • Országos Onkológiai Intézet
      • Budapest, Hungary, 1125
        • Semmelweis Egyetem AOK
      • Budapest, Hungary, 1525
        • Orszagos Koranyi TBC es Pulmonologiai Intezet
      • Debrecen, Hungary, 4032
        • Kenezy Korhaz-Rendelointezet Eu Szolgaltato Nonprofit Kft
      • Gyula, Hungary, 5703
        • Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
      • Győr, Hungary, 9024
        • Petz Aladár Megyei Oktató Kórház
      • Matrahaza, Hungary, 3233
        • Matrai Gyogyintezet
      • Szekszard, Hungary, 7100
        • Tolna Megyei Önkormányzat Balassa János Kórháza
      • Székesfehérvár, Hungary, 8000
        • Fejer Megyei Szent Gyorgy Korhaz
      • Tatabanya, Hungary, 2800
        • Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza
      • Torokbalint, Hungary, 2045
        • Tudogyogyintezet Torokbalint
      • Zalaegerszeg, Hungary, 8900
        • Zala Megyei Kórház
  • Israel
      • Beer Yaacov, Israel, 70300
        • Assaf Harofeh Medical Center
      • Jerusalem, Israel, 91120
        • Hadassah Ein Kerem Medical Center
      • Kfar-Saba, Israel, 52621
        • Sapir Medical Center Meir Hospital
      • Petah-Tikva, Israel, 49372
        • Rabin Medical Center-Beilinson Campus
      • Ramat Gan, Israel, 44281
        • Chaim Sheba Medical Center
      • Rehovot, Israel, 76100
        • Kaplan Medical Center
      • Tel Aviv, Israel, 64239
        • Tel Aviv Sourasky Medical Center
  • Italy
      • Milano, Italy, 20141
        • IEO Istituto Europeo di Oncologia
      • Perugia, Italy, 6156
        • Azienda Ospedaliera di Perugia Ospedale S.Maria della Miseri
      • Siena, Italy, 53100
        • A.O.U. Senese Policlinico Santa Maria alle Scotte
  • Poland
      • Lublin, Poland, 20-954
        • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
      • Olsztyn, Poland, 10-357
        • SP Zespol Gruzlicy i Chorob Pluc w Olsztynie
      • Otwock, Poland, 05-400
        • Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
      • Poznan, Poland, 60569
        • Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
      • Warszawa, Poland, 02-781
        • Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofia
      • Girona, Spain, 17007
        • ICO Girona - Hospital Dr Josep Trueta
      • Madrid, Spain, 28007
        • Hospital Gregorio Marañón
      • Madrid, Spain, 28050
        • START Madrid. Centro Integral Oncologico Clara Campal
      • Malaga, Spain, 29010
        • Hospital General Carlos Haya
      • Sabadell, Spain, 08208
        • Corporacio Sanitaria Parc Tauli
  • United Kingdom
      • Birmingham, United Kingdom, B15 2TH
        • Queen Elizabeth Hospital
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Hospital NHS Trust
      • Plymouth, United Kingdom, PL6 8DH
        • Plymouth Oncology Centre
      • Southampton, United Kingdom, SO16 6YD
        • Southampton University Hospitals NHS Trust
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Arizona
    • Kansas
      • Topeka, Kansas, United States, 66606
        • Cotton O'Neil Clinical Research Center
    • Kentucky
      • Louisville, Kentucky, United States, 40402
        • University of Louisville Hospital
    • Maryland
      • Cambridge, Maryland, United States, 2114
        • Massachusetts General Hospital
      • Rockville, Maryland, United States, 20850
        • Oncology/Hematology P.C.
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University
    • North Carolina
      • Fayetteville, North Carolina, United States, 72703
        • Highlands Oncology Group
    • Ohio
      • Middletown, Ohio, United States, 45042
        • Signal Point Clinical Research Center
      • Toledo, Ohio, United States, 43606
        • ProMedica Health System Inc
    • Pennsylvania
      • Willow Grove, Pennsylvania, United States, 19090
        • Abington Hematology Oncology Associates Inc
    • Texas
      • Abilene, Texas, United States, 79606
        • Texas Oncology, P.A. - Abilene (South)
      • Dallas, Texas, United States, 75246
        • Mary Crowley Medical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • gemcitabine
  • cisplatin
  • erlotinib
  • carboplatin
  • pemetrexed
  • paclitaxel
  • bevacizumab (if prescribed)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2: Progression-free Survival (PFS)
Time Frame: 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.
Approximately 15 months
Phase 3: Overall Survival (OS)
Time Frame: Approximately 27 months
OS is measured from date of randomization to date of death from any cause.
Approximately 27 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Phase 2 : Overall Survival (OS)
Time Frame: Approximately 15 months
Approximately 15 months
Phase 2 : Overall Response Rate (ORR)
Time Frame: Approximately 15 months
Approximately 15 months
Phase 3: Progression-free Survival (PFS)
Time Frame: Approximately 27 months
Approximately 27 months
Phase 3 : Overall Response Rate (ORR)
Time Frame: Approximately 27 months
Approximately 27 months
Phase 2 : Duration of response
Time Frame: Approximately 15 months
Approximately 15 months
Phase 2: Safety
Time Frame: Approximately 15 months
Approximately 15 months
Phase 3: Duration of response
Time Frame: Approximately 27 months
Approximately 27 months
Phase 3: Safety
Time Frame: Approximately 27 months
Approximately 27 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Transgene

Investigators

  • Principal Investigator: QUOIX Elisabeth, Prof, Hopitaux Universitaires de Strasbourg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

July 1, 2016

Study Registration Dates

First Submitted

June 23, 2011

First Submitted That Met QC Criteria

June 27, 2011

First Posted (Estimate)

June 28, 2011

Study Record Updates

Last Update Posted (Estimate)

January 5, 2017

Last Update Submitted That Met QC Criteria

January 4, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TG4010.14/TIME
  • 8559 (FDA)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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