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

Non-Small-Cell Lung Carcinoma Clinical Trial

— TIME  

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01383148
• Other study ID #: TG4010.14/TIME
• Secondary ID: 8559
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: June 23, 2011
• Last updated: January 4, 2017
• Start date: April 2012
• Est. completion date: July 2016

Study information

• Verified date: January 2017
• Source: Transgene
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 222
• Est. completion date: July 2016
• Est. primary completion date: July 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Carcinoma

Intervention

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.

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

Locations

Country	Name	City	State
Belgium	ZNA Middelheim	Antwerpen
Belgium	Clinique Nôtre-Dame de Grâce	Gosselies
Belgium	Centre Hospitalier de l'Ardenne	Libramont
Belgium	C. H. U. Sart-Tilman	Liège
France	CHU, Service de Pneumologie	Besancon
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 Cedex 09
France	CHU de Saint-Etienne, Hôpital Nord	Saint Etienne Cedex 02
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 cedex
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitaetsklinikum Mannheim	Mannheim
Hungary	Orszagos Koranyi TBC es Pulmonologiai Intezet	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Semmelweis Egyetem AOK	Budapest
Hungary	Kenezy Korhaz-Rendelointezet Eu Szolgaltato Nonprofit Kft	Debrecen
Hungary	Petz Aladár Megyei Oktató kórház	Gyor
Hungary	Bekes Megyei Kepviselotestulet Pandy Kalman Korhaza	Gyula
Hungary	Matrai Gyogyintezet	Matrahaza
Hungary	Fejér Megyei Szent György Kórház	Székesfehérvár
Hungary	Tolna Megyei Onkormanyzat Balassa Janos Korhaza	Szekszard
Hungary	Komarom-Esztergom Megyei Onkorm. Szent Borbala Korhaza	Tatabanya
Hungary	Tudogyogyintezet Torokbalint	Torokbalint
Hungary	Zala Megyei Korhaz	Zalaegerszeg
Israel	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
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	Azienda Ospedaliera di Perugia Ospedale S.Maria della Miseri	Perugia
Italy	A.O.U. Senese Policlinico Santa Maria alle Scotte	Siena
Poland	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	Warszawa
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
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	Malaga
Spain	Corporació Sanitària Parc Taulí	Sabadell
United Kingdom	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 States	Texas Oncology, P.A. - Abilene (South)	Abilene	Texas
United States	Massachusetts General Hospital	Cambridge	Maryland
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Highlands Oncology Group	Fayetteville	North Carolina
United States	University of Louisville Hospital	Louisville	Kentucky
United States	Signal Point Clinical Research Center	Middletown	Ohio
United States	Oncology/Hematology P.C.	Rockville	Maryland
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Washington University	St. Louis	Missouri
United States	ProMedica Health System Inc	Toledo	Ohio
United States	Cotton O'Neil Clinical Research Center	Topeka	Kansas
United States	Abington Hematology Oncology Associates Inc	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Transgene

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Phase 3: Overall Survival (OS)	OS is measured from date of randomization to date of death from any cause.	Approximately 27 months	No
Secondary	Phase 2 : Overall Survival (OS)		Approximately 15 months	No
Secondary	Phase 2 : Overall Response Rate (ORR)		Approximately 15 months	No
Secondary	Phase 3: Progression-free Survival (PFS)		Approximately 27 months	No
Secondary	Phase 3 : Overall Response Rate (ORR)		Approximately 27 months	No
Secondary	Phase 2 : Duration of response		Approximately 15 months	No
Secondary	Phase 2: Safety		Approximately 15 months	Yes
Secondary	Phase 3: Duration of response		Approximately 27 months	No
Secondary	Phase 3: Safety		Approximately 27 months	Yes

External 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.