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

NCT ID: NCT00446225

Last Updated: 2025-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-02-15
• Study Completion Date: 2012-12-31

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).

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

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

Group Type: EXPERIMENTAL

Erlotinib

Intervention Type: 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

B

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.

Group Type: ACTIVE_COMPARATOR

Carboplatin

Intervention Type: 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.

Gemcitabin

Intervention Type: 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.

Docetaxel

Intervention Type: 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.

Cisplatin

Intervention Type: 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.

Interventions

Erlotinib

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

Intervention Type: DRUG

Carboplatin

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.

Intervention Type: DRUG

Gemcitabin

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.

Intervention Type: DRUG

Docetaxel

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.

Intervention Type: DRUG

Cisplatin

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.

Intervention Type: DRUG

Other Intervention Names

Tarceva; Paraplatin; Gemzar; Taxotere; Platinol

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 ≥ 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.

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

Sponsors

Spanish Lung Cancer Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rafael Rosell i Costa, MD

Role: STUDY_CHAIR

Spanish Lung Cancer Group

Luis Paz-Ares, MD

Role: STUDY_CHAIR

Spanish Lung Cancer Group

Locations

Centre Hospitalier Universitaire D'Angers

Angers, , France

Hôpital Auguste Morvan

Brest, , France

Centre François Baclesse

Caen, , France

Centre Hospitalier René Dubos

Cergy-Pontoise, , France

Centre Hospitalier Intercommunal

Créteil, , France

Hôpital A. Mignot

Le Chesnay, , France

Centre Hospitalier Du Mans

Le Mans, , France

Centre Oscar Lambret

Lille, , France

Hôpital du Cluzeau

Limoges, , France

Centre Hospitalier Régional

Longjumeau, , France

Centre Hospitalier de Meaux

Meaux, , France

Centre Hospitalier de Mulhouse

Mulhouse, , France

Hôpital Saint Antoine

Paris, , France

Centre Hospitalier

Périgueux, , France

Centre Hospitalier de La Région D'Annecy

Pringy, , France

CHU Rennes Hôpital Ponchaillou

Rennes, , France

Centre Hosiptalier Genéral de Roanne

Roanne, , France

Institut de Cancérologie de La Loire

Saint-Priest-en-Jarez, , France

Hôpital Larrey

Toulouse, , France

CRO di Aviano

Aviano, , Italy

AO Materdomini

Catanzaro, , Italy

AOU Policlinico G. Martino

Messina, , Italy

AO Monaldi

Napoli, , Italy

Casa di Cura "La Maddalena"

Palermo, , Italy

Istituti Fisioterapici Ospitalieri

Roma, , Italy

AO S.Camillo Forlanini

Roma, , Italy

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

Roma, , Italy

PO di SS.ma Annunziata

Sassari, , Italy

H. Virgen de los Lirios

Alcoy, Alicante, Spain

H. Torrevieja Salud

Torrevieja, Alicante, Spain

ICO - H. Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital de Mataró

Mataró, Barcelona, Spain

H. Marqués de Valdecilla

Santander, Cantabria, Spain

H. Provincial de Castellón

Castellon, Castellón, Spain

Hospital Insular Gran Canaria

Las Palmas de Gran Canaria, Las Palmas, Spain

F.H.Alcorcón

Alcorcón, Madrid, Spain

H. Fuenlabrada

Fuenlabrada, Madrid, Spain

H. Son Dureta

Palma de Mallorca, Mallorca, Spain

H. Ntra. Sra. de la Candelaria

Santa Cruz de Tenerife, Tenerife, Spain

Hospital de Cruces

Barakaldo, Vizcaya, Spain

Complejo Hosp. Univ. Juan Canalejo

A Coruña, , Spain

H.G.U. Alicante

Alicante, , Spain

H. Santa Creu i Sant Pau

Barcelona, , Spain

Instituto Universitario Dexeus

Barcelona, , Spain

H.U.Vall D´Hebrón

Barcelona, , Spain

H. Clinic i Provincial

Barcelona, , Spain

H. Althaia

Barcelona, , Spain

H. Duran i Reynals-ICO

Barcelona, , Spain

H. Reina Sofía

Córdoba, , Spain

H. de Donostia

Donostia / San Sebastian, , Spain

ICO Girona -H. Dr. Josep Trueta

Girona, , Spain

H. Virgen de las Nieves

Granada, , Spain

Complejo Hospitalario de Jaén

Jaén, , Spain

H. Arnau de Vilanova

Lleida, , Spain

Hospital San Millan Y San Pedro

Logroño, , Spain

H. de la Princesa

Madrid, , Spain

H. Gregorio Marañón

Madrid, , Spain

H. Ruber Internacional

Madrid, , Spain

H.U. Puerta de Hierro

Madrid, , Spain

Fundación Jimenez Diaz

Madrid, , Spain

Hospial Clinico San Carlos

Madrid, , Spain

H. La Paz

Madrid, , Spain

H. 12 de Octubre

Madrid, , Spain

H. Ramon y Cajal

Madrid, , Spain

H. Carlos Haya

Málaga, , Spain

H.C.Universitario Virgen de la Victoria

Málaga, , Spain

H. Son Llàtzer

Palma de Mallorca, , Spain

Clinica Rotger

Palma de Mallorca, , Spain

H. Virgen del Rocío

Seville, , Spain

H. Nuestra Sra. de Valme

Seville, , Spain

H.C.U.Valencia

Valencia, , Spain

H. General U. de Valencia

Valencia, , Spain

H. Arnau de Vilanova Valencia

Valencia, , Spain

H. Dr. Peset

Valencia, , Spain

H. Miguel Servet

Zaragoza, , Spain

H. Clínico Lozano Blesa

Zaragoza, , Spain

Countries

France; Italy; Spain

References

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.

Reference Type: RESULT

PMID: 22285168 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26181014 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25806291 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24493829 (View on PubMed)

Related Links

http://www.gecp.org

Spanish Lung Cancer Group website

Other Identifiers

2006-003568-73

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EURTAC-SLCG // GECP06/01

Identifier Type: -

Identifier Source: org_study_id