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

NCT01383148 | Terminated Phase 2 DMC

• 2 other identifiers: TG4010.14/TIME8559
• Study Type: interventional
• Target: 222
• Locations: 10 countries
• Sites: 72

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.

Conditions

Non-Small-Cell Lung Carcinoma

Keywords

NSCLC

Outcome Measures

Primary Outcomes (2)

• Phase 2: Progression-free Survival (PFS)

  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)

  OS is measured from date of randomization to date of death from any cause.

  Approximately 27 months

Secondary Outcomes (8)

• 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 3 : Overall Response Rate (ORR)

  Approximately 27 months

• Phase 2 : Duration of response

  Approximately 15 months

Study Arms (2)

Arm 1 - TG4010 + first line therapy

EXPERIMENTAL

First-line therapy and maintenance therapy

Biological: TG4010

Arm 2 : Placebo + first line therapy

ACTIVE COMPARATOR

First-line therapy and maintenance therapy

Drug: placebo

Interventions

TG4010 BIOLOGICAL

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.

Arm 1 - TG4010 + first line therapy

placebo DRUG

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

Also known as: paclitaxel, carboplatin, pemetrexed, cisplatin, gemcitabine, bevacizumab (if prescribed), erlotinib

Arm 2 : Placebo + first line therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Transgene: lead

Study Sites (72)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Cotton O'Neil Clinical Research Center

Topeka, Kansas, 66606, United States

Location

University of Louisville Hospital

Louisville, Kentucky, 40402, United States

Location

Massachusetts General Hospital

Cambridge, Maryland, 2114, United States

Location

Oncology/Hematology P.C.

Rockville, Maryland, 20850, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Highlands Oncology Group

Fayetteville, North Carolina, 72703, United States

Location

Signal Point Clinical Research Center

Middletown, Ohio, 45042, United States

Location

ProMedica Health System Inc

Toledo, Ohio, 43606, United States

Location

Abington Hematology Oncology Associates Inc

Willow Grove, Pennsylvania, 19090, United States

Location

Texas Oncology, P.A. - Abilene (South)

Abilene, Texas, 79606, United States

Location

Mary Crowley Medical Research Center

Dallas, Texas, 75246, United States

Location

ZNA Middelheim

Antwerp, 2020, Belgium

Location

Clinique Nôtre-Dame de Grâce

Gosselies, 6041, Belgium

Location

Centre Hospitalier de l'Ardenne

Libramont, 6800, Belgium

Location

C. H. U. Sart-Tilman

Liège, 4000, Belgium

Location

CHU, Service de Pneumologie

Besançon, 25000, France

Location

Centre François Baclesse

Caen, 14076, France

Location

CHU de Clermont-Ferrand, Hopital Gabriel Montpied

Clermont-Ferrand, 63000, France

Location

Hôpital Pasteur - Service de médecine F- Pavillon 43

Colmar, 68000, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94010, France

Location

CHRU de Lille Hopital Calmette

Lille, 59037, France

Location

Clinique François Chénieux

Limoges, 87039, France

Location

Institut Paoli-Calmettes, Service d'oncologie médicale

Marseille, 13273, France

Location

CH Mulhouse Hopital Emile Muller Moenchsberg

Mulhouse, 68070, France

Location

Hopital Saint Joseph

Paris, 75014, France

Location

Hôpital Pontchaillou

Rennes, 35033, France

Location

CHU de Saint-Etienne, Hôpital Nord

Saint-Etienne, 42055, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42270, France

Location

Centre Médical Alfred Leune

Sainte-Feyre, 23000, France

Location

Nouvel Hôpital Civil

Strasbourg, 67000, France

Location

Centre Hospitalier Intercommunal de la Haute Saone

Vesoul, 70014, France

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitaetsklinikum Mannheim

Mannheim, 68167, Germany

Location

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

Location

Semmelweis Egyetem AOK

Budapest, 1125, Hungary

Location

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, 1525, Hungary

Location

Kenezy Korhaz-Rendelointezet Eu Szolgaltato Nonprofit Kft

Debrecen, 4032, Hungary

Location

Petz Aladár Megyei Oktató kórház

Győr, 9024, Hungary

Location

Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza

Gyula, 5703, Hungary

Location

Matrai Gyogyintezet

Mátraháza, 3233, Hungary

Location

Tolna Megyei Onkormanyzat Balassa Janos Korhaza

Szekszárd, 7100, Hungary

Location

Fejér Megyei Szent György Kórház

Székesfehérvár, 8000, Hungary

Location

Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza

Tatabánya, 2800, Hungary

Location

Tudogyogyintezet Torokbalint

Törökbálint, 2045, Hungary

Location

Zala Megyei Korhaz

Zalaegerszeg, 8900, Hungary

Location

Assaf Harofeh Medical Center

Beer Yaacov, 70300, Israel

Location

Hadassah Ein Kerem Medical Center

Jerusalem, 91120, Israel

Location

Sapir Medical Center Meir Hospital

Kfar Saba, 52621, Israel

Location

Rabin Medical Center-Beilinson Campus

Petah Tikva, 49372, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 44281, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

IEO Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Azienda Ospedaliera di Perugia Ospedale S.Maria della Miseri

Perugia, 6156, Italy

Location

A.O.U. Senese Policlinico Santa Maria alle Scotte

Siena, 53100, Italy

Location

Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie

Lublin, 20-954, Poland

Location

SP Zespol Gruzlicy i Chorob Pluc w Olsztynie

Olsztyn, 10-357, Poland

Location

Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy

Otwock, 05-400, Poland

Location

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego

Poznan, 60569, Poland

Location

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie

Warsaw, 02-781, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

ICO Girona - Hospital Dr Josep Trueta

Girona, 17007, Spain

Location

Hospital Gregorio Marañon

Madrid, 28007, Spain

Location

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospital General Carlos Haya

Málaga, 29010, Spain

Location

Corporació Sanitària Parc Taulí

Sabadell, 08208, Spain

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Velindre Hospital NHS Trust

Cardiff, CF14 2TL, United Kingdom

Location

Plymouth Oncology Centre

Plymouth, PL6 8DH, United Kingdom

Location

Southampton University Hospitals NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• Tosch C, Bastien B, Barraud L, Grellier B, Nourtier V, Gantzer M, Limacher JM, Quemeneur E, Bendjama K, Preville X. Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC. J Immunother Cancer. 2017 Sep 19;5(1):70. doi: 10.1186/s40425-017-0274-x.

  PMID: 28923084 DERIVED

• Quoix E, Lena H, Losonczy G, Forget F, Chouaid C, Papai Z, Gervais R, Ottensmeier C, Szczesna A, Kazarnowicz A, Beck JT, Westeel V, Felip E, Debieuvre D, Madroszyk A, Adam J, Lacoste G, Tavernaro A, Bastien B, Halluard C, Palanche T, Limacher JM. TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial. Lancet Oncol. 2016 Feb;17(2):212-223. doi: 10.1016/S1470-2045(15)00483-0. Epub 2015 Dec 23.

  PMID: 26727163 DERIVED

Related Links

• NSCLC
• 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. Epub 2011 Oct 21.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

TG4010; Paclitaxel; Carboplatin; Pemetrexed; Cisplatin; Gemcitabine; Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Quinazolines

Study Officials

• QUOIX Elisabeth, Prof

  Hôpitaux Universitaires de Strasbourg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: June 28, 2011
• Study Start: April 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2016
• Last Updated: January 5, 2017

Record last verified: 2017-01

Locations

US (12); IT (3); IL (7); BE (4); DE (2); HU (12); PL (5); ES (7); GB (4); FR (16)