Clinical trial NCT01383148: Phase IIB/III Of TG4010 Immunotherapy In Patients With Stage IV Non-Small Cell Lung Cancer
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Non-Small-Cell Lung Carcinoma
Keywords: NSCLC
Lead sponsor: Transgene
Sponsor class: INDUSTRY
First posted: 2011-06-28
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Phase 2: Progression-free Survival (PFS)
timeFrame: Approximately 15 months
measure: Phase 3: Overall Survival (OS)
timeFrame: Approximately 27 months
Secondary outcomes:
measure: Phase 2 : Overall Survival (OS)
timeFrame: Approximately 15 months
measure: Phase 2 : Overall Response Rate (ORR)
timeFrame: Approximately 15 months
measure: Phase 3: Progression-free Survival (PFS)
timeFrame: Approximately 27 months
measure: Phase 3 : Overall Response Rate (ORR)
timeFrame: Approximately 27 months
measure: Phase 2 : Duration of response
timeFrame: Approximately 15 months
measure: Phase 2: Safety
timeFrame: Approximately 15 months
measure: Phase 3: Duration of response
timeFrame: Approximately 27 months
measure: Phase 3: Safety
timeFrame: Approximately 27 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Topeka
country: United States
facility: Cotton O'Neil Clinical Research Center
state: Kansas
city: Louisville
country: United States
facility: University of Louisville Hospital
state: Kentucky
city: Cambridge
country: United States
facility: Massachusetts General Hospital
state: Maryland
city: Rockville
country: United States
facility: Oncology/Hematology P.C.
state: Maryland
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: North Carolina
city: Middletown
country: United States
facility: Signal Point Clinical Research Center
state: Ohio
city: Toledo
country: United States
facility: ProMedica Health System Inc
state: Ohio
city: Willow Grove
country: United States
facility: Abington Hematology Oncology Associates Inc
state: Pennsylvania
city: Abilene
country: United States
facility: Texas Oncology, P.A. - Abilene (South)
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Antwerpen
country: Belgium
facility: ZNA Middelheim
city: Gosselies
country: Belgium
facility: Clinique Nôtre-Dame de Grâce
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne
city: Liège
country: Belgium
facility: C. H. U. Sart-Tilman
city: Besancon
country: France
facility: CHU, Service de Pneumologie
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand, Hopital Gabriel Montpied
city: Colmar
country: France
facility: Hôpital Pasteur - Service de médecine F- Pavillon 43
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Lille
country: France
facility: CHRU de Lille Hopital Calmette
city: Limoges
country: France
facility: Clinique François Chénieux
city: Marseille
country: France
facility: Institut Paoli-Calmettes, Service d'oncologie médicale
city: Mulhouse
country: France
facility: CH Mulhouse Hopital Emile Muller Moenchsberg
city: Paris
country: France
facility: Hopital Saint Joseph
city: Rennes Cedex 09
country: France
facility: Hôpital Pontchaillou
city: Saint Etienne Cedex 02
country: France
facility: CHU de Saint-Etienne, Hôpital Nord
city: Saint Priest en Jarez
country: France
facility: Institut de Cancérologie Lucien Neuwirth
city: Sainte Feyre
country: France
facility: Centre Médical Alfred Leune
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil
city: Vesoul cedex
country: France
facility: Centre Hospitalier Intercommunal de la Haute Saone
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Mannheim
country: Germany
facility: Universitaetsklinikum Mannheim
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Budapest
country: Hungary
facility: Semmelweis Egyetem AOK
city: Budapest
country: Hungary
facility: Orszagos Koranyi TBC es Pulmonologiai Intezet
city: Debrecen
country: Hungary
facility: Kenezy Korhaz-Rendelointezet Eu Szolgaltato Nonprofit Kft
city: Gyula
country: Hungary
facility: Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza
city: Győr
country: Hungary
facility: Petz Aladár Megyei Oktató kórház
city: Matrahaza
country: Hungary
facility: Matrai Gyogyintezet
city: Szekszard
country: Hungary
facility: Tolna Megyei Onkormanyzat Balassa Janos Korhaza
city: Székesfehérvár
country: Hungary
facility: Fejér Megyei Szent György Kórház
city: Tatabanya
country: Hungary
facility: Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Korhaz
city: Beer Yaacov
country: Israel
facility: Assaf Harofeh Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center
city: Kfar-Saba
country: Israel
facility: Sapir Medical Center Meir Hospital
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center-Beilinson Campus
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia Ospedale S.Maria della Miseri
city: Siena
country: Italy
facility: A.O.U. Senese Policlinico Santa Maria alle Scotte
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
city: Olsztyn
country: Poland
facility: SP Zespol Gruzlicy i Chorob Pluc w Olsztynie
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy
city: Poznan
country: Poland
facility: Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Girona
country: Spain
facility: ICO Girona - Hospital Dr Josep Trueta
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: START Madrid. Centro Integral Oncologico Clara Campal
city: Malaga
country: Spain
facility: Hospital General Carlos Haya
city: Sabadell
country: Spain
facility: Corporació Sanitària Parc Taulí
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Hospital NHS Trust
city: Plymouth
country: United Kingdom
facility: Plymouth Oncology Centre
city: Southampton
country: United Kingdom
facility: Southampton University Hospitals NHS Trust
Study officials:
affiliation: Hôpitaux Universitaires de Strasbourg
name: QUOIX Elisabeth, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.