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

NCT ID: NCT01383148

Last Updated: 2017-01-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 222 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2016-07-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm 1 - TG4010 + first line therapy

First-line therapy and maintenance therapy

Group Type: EXPERIMENTAL

TG4010

Intervention Type: 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 2 : Placebo + first line therapy

First-line therapy and maintenance therapy

Group Type: ACTIVE_COMPARATOR

placebo

Intervention Type: 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

Interventions

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.

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

Other Intervention Names

paclitaxel; carboplatin; pemetrexed; cisplatin; gemcitabine; bevacizumab (if prescribed); erlotinib

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Transgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

QUOIX Elisabeth, Prof

Role: PRINCIPAL_INVESTIGATOR

Hôpitaux Universitaires de Strasbourg

Locations

Mayo Clinic Arizona

Scottsdale, Arizona, United States

Cotton O'Neil Clinical Research Center

Topeka, Kansas, United States

University of Louisville Hospital

Louisville, Kentucky, United States

Massachusetts General Hospital

Cambridge, Maryland, United States

Oncology/Hematology P.C.

Rockville, Maryland, United States

Washington University

St Louis, Missouri, United States

Highlands Oncology Group

Fayetteville, North Carolina, United States

Signal Point Clinical Research Center

Middletown, Ohio, United States

ProMedica Health System Inc

Toledo, 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

Antwerp, , 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

Besançon, , 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

Hopital Saint Joseph

Paris, , France

Hôpital Pontchaillou

Rennes, , France

CHU de Saint-Etienne, Hôpital Nord

Saint-Etienne, , France

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, , France

Centre Médical Alfred Leune

Sainte-Feyre, , France

Nouvel Hôpital Civil

Strasbourg, , France

Centre Hospitalier Intercommunal de la Haute Saone

Vesoul, , France

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Universitaetsklinikum Mannheim

Mannheim, , Germany

Orszagos Onkologiai Intezet

Budapest, , Hungary

Semmelweis Egyetem AOK

Budapest, , Hungary

Orszagos Koranyi TBC es Pulmonologiai Intezet

Budapest, , Hungary

Kenezy Korhaz-Rendelointezet Eu Szolgaltato Nonprofit Kft

Debrecen, , Hungary

Petz Aladár Megyei Oktató kórház

Győr, , Hungary

Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza

Gyula, , Hungary

Matrai Gyogyintezet

Mátraháza, , Hungary

Tolna Megyei Onkormanyzat Balassa Janos Korhaza

Szekszárd, , Hungary

Fejér Megyei Szent György Kórház

Székesfehérvár, , Hungary

Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza

Tatabánya, , Hungary

Tudogyogyintezet Torokbalint

Törökbálint, , Hungary

Zala Megyei Korhaz

Zalaegerszeg, , Hungary

Assaf Harofeh Medical Center

Beer Yaacov, , Israel

Hadassah Ein Kerem Medical Center

Jerusalem, , Israel

Sapir Medical Center Meir Hospital

Kfar Saba, , Israel

Rabin Medical Center-Beilinson Campus

Petah Tikva, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Kaplan Medical Center

Rehovot, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

IEO Istituto Europeo di Oncologia

Milan, , 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

SP Zespol Gruzlicy i Chorob Pluc w Olsztynie

Olsztyn, , Poland

Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy

Otwock, , Poland

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego

Poznan, , Poland

Centrum Onkologii-Instytut im. M. Sklodowskiej Curie

Warsaw, , Poland

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

ICO Girona - Hospital Dr Josep Trueta

Girona, , Spain

Hospital Gregorio Marañon

Madrid, , Spain

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, , Spain

Hospital General Carlos Haya

Málaga, , Spain

Corporació Sanitària Parc Taulí

Sabadell, , Spain

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Velindre Hospital NHS Trust

Cardiff, , United Kingdom

Plymouth Oncology Centre

Plymouth, , United Kingdom

Southampton University Hospitals NHS Trust

Southampton, , United Kingdom

Countries

United States; Belgium; France; Germany; Hungary; Israel; Italy; Poland; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 28923084 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26727163 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed?term=nsclc

NSCLC

http://www.ncbi.nlm.nih.gov/pubmed/22019520

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.

Other Identifiers

8559

Identifier Type: OTHER

Identifier Source: secondary_id

TG4010.14/TIME

Identifier Type: -

Identifier Source: org_study_id