Phase III Study (Tarceva®) vs Chemotherapy to Treat Advanced Non-Small Cell Lung Cancer in Patients With Mutations in the TK Domain of EGFR

NCT00446225 | Completed Phase 3 Results DMC

• 2 other identifiers: EURTAC-SLCG // GECP06/012006-003568-73
• Study Type: interventional
• Target: 174
• Locations: 3 countries
• Sites: 76

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

Lung; cancer; EGFR; Epidermal Growth Factor Receptor; tyrosine kinase; Tarceva®; Erlotinib

Outcome Measures

Primary Outcomes (1)

• Progression Free-survival

  The time from enrollment in the study to tumor progression or death from any cause (whichever occurs first)

  From the date of randomization to the date of last follow up, assessed up to 24 months

Secondary Outcomes (3)

• Objective Response

  From the date of randomization to the date of last follow up, assessed up to 24 months

• Overall Survival

  From the date of randomization to the date of last follow up, assessed up to 24 months

• Molecular Markers Related to EGFR and Study Pathology

  At baseline

Study Arms (2)

A

EXPERIMENTAL

Erlotinib (Tarceva)150 mg /day Patients will receive treatment until disease progression or unacceptable toxicity. For all practical effects a treatment cycle will be defined as three weeks of continuous treatment with erlotinib

Drug: Erlotinib

B

ACTIVE COMPARATOR

4 cycles of Chemotherapy: Cisplatin / Gemcitabine; Cisplatin /Docetaxel; Carboplatin / Gemcitabine; Carboplatin / Docetaxel. \- Cisplatin plus docetaxel: cisplatin 75 mg/m2 i.v. day 1 and docetaxel 75 mg/m2 i.v. day 1. Repeat cycles every 3 weeks. \- Cisplatin plus gemcitabine: Cisplatin 75 mg/m2 i.v. on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8. Repeat cycles every 3 weeks. In the case of patients not eligible for treatment with cisplatin, cisplatin can be replaced by carboplatin. The schedules will be the following: Docetaxel 75 mg/m2 day 1 and carboplatin AUC = 6 day 1, every 21 days. Gemcitabine 1000 mg/m2 days 1 and 8 and carboplatin AUC = 5 day 1, every 21 days. Patients in the chemotherapy arm will receive the treatment until disease progression or unacceptable toxicity occurs, or until a maximum of 4 treatment cycles are given.

Drug: Carboplatin; Drug: Gemcitabin; Drug: Docetaxel; Drug: Cisplatin

Interventions

Erlotinib DRUG

150 mg/day Patients will receive treatment until disease progression or unacceptable toxicity. For all practical effects a treatment cycle will be defined as three weeks of continuous treatment with erlotinib

Also known as: Tarceva

A

Carboplatin DRUG

Gemcitabine 1000 mg/m2 days 1 and 8 and Carboplatin AUC = 5 day 1, every 21 days. Docetaxel (75 mg/m2) /carboplatin (AUC=6); Gemcitabine (1000 mg/m2; day 1 and 8) / Carboplatin (AUC=5) Patients in the chemotherapy arm will receive the treatment until disease progression or unacceptable toxicity occurs, or until a maximum of 4 treatment cycles are given.

Also known as: Paraplatin

B

Gemcitabin DRUG

Cisplatin (75 mg/m2) / Gemcitabine (1250 mg/m2; day 1 and 8) Patients in the chemotherapy arm will receive the treatment until disease progression or unacceptable toxicity occurs, or until a maximum of 4 treatment cycles are given.

Also known as: Gemzar

B

Docetaxel DRUG

Cisplatin (75 mg/m2) / Docetaxel (75 mg/m2) Patients in the chemotherapy arm will receive the treatment until disease progression or unacceptable toxicity occurs, or until a maximum of 4 treatment cycles are given.

Also known as: Taxotere

B

Cisplatin DRUG

Cisplatin (75 mg/m2) / Docetaxel (75 mg/m2) Patients in the chemotherapy arm will receive the treatment until disease progression or unacceptable toxicity occurs, or until a maximum of 4 treatment cycles are given.

Also known as: Platinol

B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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 ≥ 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.
• 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.

Sponsors & Collaborators

• Spanish Lung Cancer Group: lead

Study Sites (76)

Centre Hospitalier Universitaire D'Angers

Angers, France

Location

Hôpital Auguste Morvan

Brest, 29200, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre Hospitalier René Dubos

Cergy-Pontoise, France

Location

Centre Hospitalier Intercommunal

Créteil, 94010, France

Location

Hôpital A. Mignot

Le Chesnay, France

Location

Centre Hospitalier Du Mans

Le Mans, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Hôpital du Cluzeau

Limoges, 87042, France

Location

Centre Hospitalier Régional

Longjumeau, France

Location

Centre Hospitalier de Meaux

Meaux, France

Location

Centre Hospitalier de Mulhouse

Mulhouse, France

Location

Hôpital Saint Antoine

Paris, 75571, France

Location

Centre Hospitalier

Périgueux, France

Location

Centre Hospitalier de La Région D'Annecy

Pringy, France

Location

CHU Rennes Hôpital Ponchaillou

Rennes, 35033, France

Location

Centre Hosiptalier Genéral de Roanne

Roanne, France

Location

Institut de Cancérologie de La Loire

Saint-Priest-en-Jarez, France

Location

Hôpital Larrey

Toulouse, 31059, France

Location

CRO di Aviano

Aviano, 33081, Italy

Location

AO Materdomini

Catanzaro, 88100, Italy

Location

AOU Policlinico G. Martino

Messina, 98125, Italy

Location

AO Monaldi

Napoli, 80131, Italy

Location

Casa di Cura "La Maddalena"

Palermo, 90146, Italy

Location

Istituti Fisioterapici Ospitalieri

Roma, 00128, Italy

Location

AO S.Camillo Forlanini

Roma, 00149, Italy

Location

Università di Roma "La Sapienza" Az.Policlinico Umb.I°

Roma, 00161, Italy

Location

PO di SS.ma Annunziata

Sassari, 07100, Italy

Location

H. Virgen de los Lirios

Alcoy, Alicante, 03804, Spain

Location

H. Torrevieja Salud

Torrevieja, Alicante, 03193, Spain

Location

ICO - H. Germans Trias i Pujol

Badalona, Barcelona, Spain

Location

Hospital de Mataró

Mataró, Barcelona, 08304, Spain

Location

H. Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

H. Provincial de Castellón

Castellon, Castellón, 12002, Spain

Location

Hospital Insular Gran Canaria

Las Palmas de Gran Canaria, Las Palmas, 35016, Spain

Location

F.H.Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

H. Fuenlabrada

Fuenlabrada, Madrid, 28942, Spain

Location

H. Son Dureta

Palma de Mallorca, Mallorca, 07014, Spain

Location

H. Ntra. Sra. de la Candelaria

Santa Cruz de Tenerife, Tenerife, 38010, Spain

Location

Hospital de Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Complejo Hosp. Univ. Juan Canalejo

A Coruña, 15006, Spain

Location

H.G.U. Alicante

Alicante, Spain

Location

H. Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Instituto Universitario Dexeus

Barcelona, 08028, Spain

Location

H.U.Vall D´Hebrón

Barcelona, 08035, Spain

Location

H. Clinic i Provincial

Barcelona, 08036, Spain

Location

H. Althaia

Barcelona, 08243, Spain

Location

H. Duran i Reynals-ICO

Barcelona, 08907, Spain

Location

H. Reina Sofía

Córdoba, 14004, Spain

Location

H. de Donostia

Donostia / San Sebastian, 20014, Spain

Location

ICO Girona -H. Dr. Josep Trueta

Girona, 17007, Spain

Location

H. Virgen de las Nieves

Granada, 18014, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

H. Arnau de Vilanova

Lleida, 25198, Spain

Location

Hospital San Millan Y San Pedro

Logroño, Spain

Location

H. de la Princesa

Madrid, 28006, Spain

Location

H. Gregorio Marañón

Madrid, 28007, Spain

Location

H. Ruber Internacional

Madrid, 28034, Spain

Location

H.U. Puerta de Hierro

Madrid, 28035, Spain

Location

Fundación Jimenez Diaz

Madrid, 28040, Spain

Location

Hospial Clinico San Carlos

Madrid, 28040, Spain

Location

H. La Paz

Madrid, 28046, Spain

Location

H. 12 de Octubre

Madrid, Spain

Location

H. Ramon y Cajal

Madrid, Spain

Location

H. Carlos Haya

Málaga, 29010, Spain

Location

H.C.Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

H. Son Llàtzer

Palma de Mallorca, 07198, Spain

Location

Clinica Rotger

Palma de Mallorca, Spain

Location

H. Virgen del Rocío

Seville, 41013, Spain

Location

H. Nuestra Sra. de Valme

Seville, 41014, Spain

Location

H.C.U.Valencia

Valencia, 46010, Spain

Location

H. General U. de Valencia

Valencia, 46014, Spain

Location

H. Arnau de Vilanova Valencia

Valencia, 46015, Spain

Location

H. Dr. Peset

Valencia, 46017, Spain

Location

H. Miguel Servet

Zaragoza, 50009, Spain

Location

H. Clínico Lozano Blesa

Zaragoza, 59009, Spain

Location

Related Publications (4)

• 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.

  PMID: 22285168 RESULT

• 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.

  PMID: 26181014 DERIVED

• 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.

  PMID: 25806291 DERIVED

• 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.

  PMID: 24493829 DERIVED

Related Links

• Spanish Lung Cancer Group website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

Erlotinib Hydrochloride; Carboplatin; Gemcitabine; Docetaxel; Cisplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Eva Pereira
• Organization: Fundación GECP

epereira@gecp.org

+34934302006

Study Officials

• Rafael Rosell i Costa, MD

  Spanish Lung Cancer Group

  STUDY CHAIR

• Luis Paz-Ares, MD

  Spanish Lung Cancer Group

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2007
• First Posted: March 12, 2007
• Study Start: February 15, 2007
• Primary Completion: April 11, 2012
• Study Completion: December 1, 2012
• Last Updated: March 5, 2025
• Results First Posted: March 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (48); FR (19); IT (9)