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

Non-Small Cell Lung Cancer Clinical Trial

— EURTAC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00446225
• Other study ID #: EURTAC-SLCG // GECP06/01
• Secondary ID: 2006-003568-73
• Status: Completed
• Phase: Phase 3
• Start date: February 2007
• Est. completion date: December 2012

Study information

• Verified date: June 2022
• Source: Spanish Lung Cancer Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: December 2012
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• 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
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
France	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	Creteil
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	Perigueux
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	St-Priest en Jarez
France	Hôpital Larrey	Toulouse
Italy	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	AO S.Camillo Forlanini	Roma
Italy	Istituti Fisioterapici Ospitalieri	Roma
Italy	Università di Roma "La Sapienza" Az.Policlinico Umb.I°	Roma
Italy	PO di SS.ma Annunziata	Sassari
Spain	F.H.Alcorcón	Alcorcon	Madrid
Spain	H. Virgen de los Lirios	Alcoy	Alicante
Spain	H.G.U. Alicante	Alicante
Spain	ICO - H. Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital de Cruces	Baracaldo	Vizcaya
Spain	H. Althaia	Barcelona
Spain	H. Clinic i Provincial	Barcelona
Spain	H. Duran i Reynals-ICO	Barcelona
Spain	H. Santa Creu i Sant Pau	Barcelona
Spain	H.U.Vall D´Hebrón	Barcelona
Spain	Instituto Universitario Dexeus	Barcelona
Spain	H. Provincial de Castellón	Castelló de la Plana	Castellón
Spain	H. Reina Sofía	Córdoba
Spain	H. Fuenlabrada	Fuenlabrada	Madrid
Spain	ICO Girona -H. Dr. Josep Trueta	Girona
Spain	H. Virgen de las Nieves	Granada
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Complejo Hosp. Univ. Juan Canalejo	La Coruña
Spain	Hospital Insular Gran Canaria	Las Palmas De Gran Canaria	Las Palmas
Spain	H. Arnau de Vilanova	Lérida
Spain	Hospital San Millan Y San Pedro	Logroño
Spain	Fundación Jimenez Diaz	Madrid
Spain	H. 12 de Octubre	Madrid
Spain	H. de la Princesa	Madrid
Spain	H. Gregorio Marañón	Madrid
Spain	H. La Paz	Madrid
Spain	H. Ramon y Cajal	Madrid
Spain	H. Ruber Internacional	Madrid
Spain	H.U. Puerta de Hierro	Madrid
Spain	Hospial Clinico San Carlos	Madrid
Spain	H. Carlos Haya	Málaga
Spain	H.C.Universitario Virgen de la Victoria	Málaga
Spain	Hospital de Mataró	Mataró	Barcelona
Spain	Clinica Rotger	Palma de Mallorca
Spain	H. Son Dureta	Palma de Mallorca	Mallorca
Spain	H. Son Llàtzer	Palma de Mallorca
Spain	H. de Donostia	San Sebastian
Spain	H. Ntra. Sra. de la Candelaria	Santa Cruz de Tenerife	Tenerife
Spain	H. Marqués de Valdecilla	Santander	Cantabria
Spain	H. Nuestra Sra. de Valme	Sevilla
Spain	H. Virgen del Rocío	Sevilla
Spain	H. Torrevieja Salud	Torrevieja	Alicante
Spain	H. Arnau de Vilanova Valencia	Valencia
Spain	H. Dr. Peset	Valencia
Spain	H. General U. de Valencia	Valencia
Spain	H.C.U.Valencia	Valencia
Spain	H. Clínico Lozano Blesa	Zaragoza
Spain	H. Miguel Servet	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Spanish Lung Cancer Group

Countries where clinical trial is conducted

France,  Italy,  Spain, 

References & Publications (1)

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, Regu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective Response	The objective response rate is defined as the percentage of patients who attain complete response (CR) or partial response (PR); response will be evaluated following RECIST criteria.	From the date of randomization to the date of last follow up, assessed up to 24 months
Secondary	One year survival	Proportion of patients who are still alive one year after enrollment in the study.	From the date of randomization to the one year after initiation of treatment.
Secondary	Overall survival	Overall survival will be assessed from the date of enrollment in the study until the date of death from any cause. Patients lost to follow-up will be censured on the date of the last follow-up visit.	From the date of randomization to the date of last follow up, assessed up to 24 months
Secondary	Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	Occurrence and severity of adverse events, with severity determined by NCI CTCAE v3.0 criteria	From the subject's written consent to participate in the study through 30 days after the final administration of the drug
Secondary	Life quality	Changes in the scores obtained with the LCSS validated questionnaire throughout the course of the study will be analyzed to assess change in the patient's quality of life.	At baseline, every 3 weeks during treatment period, end of treatment visit and every 3 months during follow up period.
Secondary	Molecular markers related to EGFR and study pathology	The study of mutations in serum (serum DNA)	At baseline, after 6 months of inclusion and at progression.

External Links

•   Spanish Lung Cancer Group website