Clinical trial NCT00446225: Phase III Study (Tarceva®) vs Chemotherapy to Treat Advanced Non-Small Cell Lung Cancer in Patients With Mutations in the TK Domain of EGFR
Official title: Phase III, Multicenter, Open-label, Randomized Trial of Tarceva® vs Chemotherapy in Patients With Advanced NSCLC With Mutations in the TK Domain of the EGFR
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Lung
cancer
EGFR
Epidermal Growth Factor Receptor
tyrosine kinase
Tarceva®
Erlotinib
Lead sponsor: Spanish Lung Cancer Group
Sponsor class: OTHER
First posted: 2007-03-12
Enrollment: 174
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: A Phase III, multicenter, open-label, randomized trial of Erlotinib (Tarceva®) versus chemotherapy in patients with advanced NSCLC with mutations in the Tyrosine Kinase (TK) domain of the EGFR.

Detailed description: This is a multicenter, phase III, randomized, open-label clinical trial.

146 patients with a diagnosis of advanced (stage IIIB and stage IV), non-squamous-cell, non-small-cell pulmonary carcinoma not treated previously for their disease with chemotherapy who present mutation in the tyrosine kinase domain of the epidermal growth factor receptor, EGFR will be recluted.

The primary objective is to compare the progression-free survival in both treatment arms of the study (conventional chemotherapy vs. erlotinib) in patients with non-squamous-cell, non-small-cell lung cancer (NSCLC) in advanced stage (stages IIIB and stage IV) who have not received previous chemotherapy for their disease and who present mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR).

Eligibility criteria: Inclusion criteria:

* Informed consent
* Histologically confirmed diagnosis of NSCLC, non epidermoid, stage IV or IIIB with pleural effusion, or N3 tumours not candidate for thoracic radiotherapy, harbouring deletions in the exon 19 or mutation in the exon 21 in the TK of the EGFR.
* Either measurable or evaluable disease.
* Age \> 18 years.
* ECOG performance status \< 2.
* Adequate bone marrow function
* Adequate renal function
* Adequate hepatic function
* Patients must be accessible for treatment and follow-up.
* Patients capable of following an adequate therapeutic compliance
* Women of child bearing potential: negative pregnancy test.
* Patients of both genders at a fertile age, including those women having their last menstruation within the two previous years, must follow effective contraceptive measures.
* Ability to swallow.
* Patients with asymptomatic brain metastasis and stable with medical treatment will be eligible for the study. Patients having received radiotherapy for their brain metastasis prior to the systemic treatment for the NSCLC will be also eligible.
* Absence of gastrointestinal tract problems

Exclusion criteria:

* Pregnant or lactating women.
* Women of child bearing potential having a positive pregnancy test in the basal visit or not accomplishing the test.
* Patients of both genders sexually active (at a fertile age) not following contraceptive measures during the study.
* Prior chemotherapy for metastatic disease. Both prior neoadjuvant and adjuvant chemotherapy allowed provided that completed â‰¥ 6 months before entering the study.
* Prior treatment with EGFR targeted therapies.
* Patients may have received radiotherapy, provided that the irradiated lesion is not the only evaluable lesion for response and completed before entering the study.
* Prior experimental pharmacological agent within the 3 weeks prior to the inclusion of the study.
* Any significant ophthalmologic impairment of the eye surface. Use of contact lenses is not recommended.
* Pre-existing motor or sensorial neurotoxicity grade \> 2, according to the NCI-CTC criteria.
* Evidence of spinal cord compression.
* Inability to take oral medication and surgical procedures affecting the absorption or implying intravenous or parenteral feeding.
* Any other severe disease or clinical conditions, as, but not only:

  * Unstable cardiopathy despite treatment, myocardial infarction within the 6 months before entering the study
  * History of significant neurological or psychiatric disorders, including dementia and epileptic seizures.
  * Uncontrolled active infection.
  * Uncontrolled peptic ulcer.
  * Unstable diabetes mellitus or any other contraindication for treatment with corticosteroids.
  * AST and/or ALT \> 1.5 x UNL associated to alkaline phosphatase \> 2.5 x UNL.
  * Any other underlying severe process affecting the ability to take part in the study.
* Absolute contraindication for steroids.
* Dementia or significant mental disorder interfering the understanding and giving the informed consent.
* History of other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, radically treated prostatic carcinoma with good prognostic (Gleason = 6). History of other curatively treated malignancy and no evidence of disease within the past 5 years.

Primary outcomes:
measure: Progression Free-survival
timeFrame: From the date of randomization to the date of last follow up, assessed up to 24 months
Secondary outcomes:
measure: Objective Response
timeFrame: From the date of randomization to the date of last follow up, assessed up to 24 months
measure: Overall Survival
timeFrame: From the date of randomization to the date of last follow up, assessed up to 24 months
measure: Molecular Markers Related to EGFR and Study Pathology
timeFrame: At baseline
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Hospitalier Universitaire D'Angers
city: Brest
country: France
facility: Hôpital Auguste Morvan
city: Caen
country: France
facility: Centre François Baclesse
city: Cergy Pontoise
country: France
facility: Centre Hospitalier René Dubos
city: Creteil
country: France
facility: Centre Hospitalier Intercommunal
city: Le Chesnay
country: France
facility: Hôpital A. Mignot
city: Le Mans
country: France
facility: Centre Hospitalier Du Mans
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: Hôpital du Cluzeau
city: Longjumeau
country: France
facility: Centre Hospitalier Régional
city: Meaux
country: France
facility: Centre Hospitalier de Meaux
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Perigueux
country: France
facility: Centre Hospitalier
city: Pringy
country: France
facility: Centre Hospitalier de La Région D'Annecy
city: Rennes
country: France
facility: CHU Rennes Hôpital Ponchaillou
city: Roanne
country: France
facility: Centre Hosiptalier Genéral de Roanne
city: St-Priest en Jarez
country: France
facility: Institut de Cancérologie de La Loire
city: Toulouse
country: France
facility: Hôpital Larrey
city: Aviano
country: Italy
facility: CRO di Aviano
city: Catanzaro
country: Italy
facility: AO Materdomini
city: Messina
country: Italy
facility: AOU Policlinico G. Martino
city: Napoli
country: Italy
facility: AO Monaldi
city: Palermo
country: Italy
facility: Casa di Cura "La Maddalena"
city: Roma
country: Italy
facility: Istituti Fisioterapici Ospitalieri
city: Roma
country: Italy
facility: AO S.Camillo Forlanini
city: Roma
country: Italy
facility: Università di Roma "La Sapienza" Az.Policlinico Umb.I°
city: Sassari
country: Italy
facility: PO di SS.ma Annunziata
city: Alcoy
country: Spain
facility: H. Virgen de los Lirios
state: Alicante
city: Torrevieja
country: Spain
facility: H. Torrevieja Salud
state: Alicante
city: Badalona
country: Spain
facility: ICO - H. Germans Trias i Pujol
state: Barcelona
city: Mataró
country: Spain
facility: Hospital de Mataró
state: Barcelona
city: Santander
country: Spain
facility: H. Marqués de Valdecilla
state: Cantabria
city: Castelló de la Plana
country: Spain
facility: H. Provincial de Castellón
state: Castellón
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Insular Gran Canaria
state: Las Palmas
city: Alcorcon
country: Spain
facility: F.H.Alcorcón
state: Madrid
city: Fuenlabrada
country: Spain
facility: H. Fuenlabrada
state: Madrid
city: Palma de Mallorca
country: Spain
facility: H. Son Dureta
state: Mallorca
city: Santa Cruz de Tenerife
country: Spain
facility: H. Ntra. Sra. de la Candelaria
state: Tenerife
city: Baracaldo
country: Spain
facility: Hospital de Cruces
state: Vizcaya
city: Alicante
country: Spain
facility: H.G.U. Alicante
city: Barcelona
country: Spain
facility: H. Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Instituto Universitario Dexeus
city: Barcelona
country: Spain
facility: H.U.Vall D´Hebrón
city: Barcelona
country: Spain
facility: H. Clinic i Provincial
city: Barcelona
country: Spain
facility: H. Althaia
city: Barcelona
country: Spain
facility: H. Duran i Reynals-ICO
city: Córdoba
country: Spain
facility: H. Reina Sofía
city: Girona
country: Spain
facility: ICO Girona -H. Dr. Josep Trueta
city: Granada
country: Spain
facility: H. Virgen de las Nieves
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: La Coruña
country: Spain
facility: Complejo Hosp. Univ. Juan Canalejo
city: Logroño
country: Spain
facility: Hospital San Millan Y San Pedro
city: Lérida
country: Spain
facility: H. Arnau de Vilanova
city: Madrid
country: Spain
facility: H. de la Princesa
city: Madrid
country: Spain
facility: H. Gregorio Marañón
city: Madrid
country: Spain
facility: H. Ruber Internacional
city: Madrid
country: Spain
facility: H.U. Puerta de Hierro
city: Madrid
country: Spain
facility: Fundación Jimenez Diaz
city: Madrid
country: Spain
facility: Hospial Clinico San Carlos
city: Madrid
country: Spain
facility: H. La Paz
city: Madrid
country: Spain
facility: H. 12 de Octubre
city: Madrid
country: Spain
facility: H. Ramon y Cajal
city: Málaga
country: Spain
facility: H. Carlos Haya
city: Málaga
country: Spain
facility: H.C.Universitario Virgen de la Victoria
city: Palma de Mallorca
country: Spain
facility: H. Son Llàtzer
city: Palma de Mallorca
country: Spain
facility: Clinica Rotger
city: San Sebastian
country: Spain
facility: H. de Donostia
city: Sevilla
country: Spain
facility: H. Virgen del Rocío
city: Sevilla
country: Spain
facility: H. Nuestra Sra. de Valme
city: Valencia
country: Spain
facility: H.C.U.Valencia
city: Valencia
country: Spain
facility: H. General U. de Valencia
city: Valencia
country: Spain
facility: H. Arnau de Vilanova Valencia
city: Valencia
country: Spain
facility: H. Dr. Peset
city: Zaragoza
country: Spain
facility: H. Miguel Servet
city: Zaragoza
country: Spain
facility: H. Clínico Lozano Blesa
Study officials:
affiliation: Spanish Lung Cancer Group
name: Rafael Rosell i Costa, MD
role: STUDY_CHAIR
affiliation: Spanish Lung Cancer Group
name: Luis Paz-Ares, MD
role: STUDY_CHAIR
References:
citation: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group in collaboration with Groupe Francais de Pneumo-Cancerologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X. Epub 2012 Jan 26.
citation: Karachaliou N, Mayo-de las Casas C, Queralt C, de Aguirre I, Melloni B, Cardenal F, Garcia-Gomez R, Massuti B, Sanchez JM, Porta R, Ponce-Aix S, Moran T, Carcereny E, Felip E, Bover I, Insa A, Reguart N, Isla D, Vergnenegre A, de Marinis F, Gervais R, Corre R, Paz-Ares L, Morales-Espinosa D, Viteri S, Drozdowskyj A, Jordana-Ariza N, Ramirez-Serrano JL, Molina-Vila MA, Rosell R; Spanish Lung Cancer Group. Association of EGFR L858R Mutation in Circulating Free DNA With Survival in the EURTAC Trial. JAMA Oncol. 2015 May;1(2):149-57. doi: 10.1001/jamaoncol.2014.257.
citation: Karachaliou N, Gimenez-Capitan A, Drozdowskyj A, Viteri S, Moran T, Carcereny E, Massuti B, Vergnenegre A, de Marinis F, Molina MA, Teixido C, Rosell R. ROR1 as a novel therapeutic target for EGFR-mutant non-small-cell lung cancer patients with the EGFR T790M mutation. Transl Lung Cancer Res. 2014 Jun;3(3):122-30. doi: 10.3978/j.issn.2218-6751.2014.03.02.
citation: Costa C, Molina MA, Drozdowskyj A, Gimenez-Capitan A, Bertran-Alamillo J, Karachaliou N, Gervais R, Massuti B, Wei J, Moran T, Majem M, Felip E, Carcereny E, Garcia-Campelo R, Viteri S, Taron M, Ono M, Giannikopoulos P, Bivona T, Rosell R. The impact of EGFR T790M mutations and BIM mRNA expression on outcome in patients with EGFR-mutant NSCLC treated with erlotinib or chemotherapy in the randomized phase III EURTAC trial. Clin Cancer Res. 2014 Apr 1;20(7):2001-10. doi: 10.1158/1078-0432.CCR-13-2233. Epub 2014 Feb 3.