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

Phase 3

Completed

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: Erlotinib; Drug: Carboplatin; Drug: Gemcitabin; Drug: Docetaxel; Drug: Cisplatin

• Registration Number: NCT00446225
• Lead Sponsor: Spanish Lung Cancer Group

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).

Study Timeline

• Study Start: 2007-02-15
• Study First Submitted: 2007-03-08
• Study First Submitted QC: 2007-03-09
• Study First Posted: 2007-03-12
• Primary Completion: 2012-04-11
• Study Completion: 2012-12
• Status Verified: 2025-02
• Results First Submitted: 2025-02-06
• Results First Submitted QC: 2025-02-27
• Last Update Submitted: 2025-02-27
• Results First Posted: 2025-03-05
• Last Update Posted: 2025-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 174

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Erlotinib	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
B	Carboplatin	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.
B	Gemcitabin	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.
B	Docetaxel	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.
B	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Progression Free-survival	From the date of randomization to the date of last follow up, assessed up to 24 months	The time from enrollment in the study to tumor progression or death from any cause (whichever occurs first)

Secondary Outcome Measures

Name	Time	Method
Objective Response	From the date of randomization to the date of last follow up, assessed up to 24 months	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 version 1.0.; Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on study.
Overall Survival	From the date of randomization to the date of last follow up, assessed up to 24 months	Overall Survival (OS) is defined as the time, in months, from the inclusion date to the death date. A patient is censored at the last contact date if he/she does not die.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.
Molecular Markers Related to EGFR and Study Pathology	At baseline	The study of mutations in serum (serum DNA). This exploratory analysis was performed to determine whether EGFR mutations can reliably be detected in serum thereby reducing the requirement for invasive techniques as well as to enable detection of mutations in patients where no tumor biopsy samples are available.

Trial Locations

Locations (76)

Centre Hospitalier René Dubos; 🇫🇷 Cergy Pontoise, France

Centre Hospitalier Du Mans; 🇫🇷 Le Mans, France

Centre Oscar Lambret; 🇫🇷 Lille, France

Hôpital du Cluzeau; 🇫🇷 Limoges, France

AOU Policlinico G. Martino; 🇮🇹 Messina, Italy

AO Materdomini; 🇮🇹 Catanzaro, Italy

H. Provincial de Castellón; 🇪🇸 Castelló de la Plana, Castellón, Spain

H. Ntra. Sra. de la Candelaria; 🇪🇸 Santa Cruz de Tenerife, Tenerife, Spain

H. Duran i Reynals-ICO; 🇪🇸 Barcelona, Spain

H. Reina Sofía; 🇪🇸 Córdoba, Spain

H. Virgen de las Nieves; 🇪🇸 Granada, Spain

Complejo Hospitalario de Jaén; 🇪🇸 Jaén, Spain

H. Arnau de Vilanova; 🇪🇸 Lérida, Spain

H. Ruber Internacional; 🇪🇸 Madrid, Spain

H.U. Puerta de Hierro; 🇪🇸 Madrid, Spain

Hospial Clinico San Carlos; 🇪🇸 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.C.U.Valencia; 🇪🇸 Valencia, Spain

H. Nuestra Sra. de Valme; 🇪🇸 Sevilla, Spain

H. General U. de Valencia; 🇪🇸 Valencia, Spain

H. Arnau de Vilanova Valencia; 🇪🇸 Valencia, Spain

H. Miguel Servet; 🇪🇸 Zaragoza, Spain

H. Clínico Lozano Blesa; 🇪🇸 Zaragoza, Spain

Hôpital Auguste Morvan; 🇫🇷 Brest, France

Centre François Baclesse; 🇫🇷 Caen, France

Centre Hospitalier Intercommunal; 🇫🇷 Creteil, France

Centre Hospitalier Régional; 🇫🇷 Longjumeau, France

Hôpital Saint Antoine; 🇫🇷 Paris, France

Centre Hospitalier; 🇫🇷 Perigueux, France

Casa di Cura "La Maddalena"; 🇮🇹 Palermo, Italy

Università di Roma "La Sapienza" Az.Policlinico Umb.I°; 🇮🇹 Roma, Italy

H. Torrevieja Salud; 🇪🇸 Torrevieja, Alicante, Spain

H. Virgen de los Lirios; 🇪🇸 Alcoy, Alicante, Spain

F.H.Alcorcón; 🇪🇸 Alcorcon, Madrid, Spain

H. Fuenlabrada; 🇪🇸 Fuenlabrada, Madrid, Spain

H. Son Dureta; 🇪🇸 Palma de Mallorca, Mallorca, Spain

Hospital de Cruces; 🇪🇸 Baracaldo, Vizcaya, Spain

H.G.U. Alicante; 🇪🇸 Alicante, Spain

H. Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

H.U.Vall D´Hebrón; 🇪🇸 Barcelona, Spain

Instituto Universitario Dexeus; 🇪🇸 Barcelona, Spain

H. Clinic i Provincial; 🇪🇸 Barcelona, Spain

H. Althaia; 🇪🇸 Barcelona, Spain

ICO Girona -H. Dr. Josep Trueta; 🇪🇸 Girona, Spain

Complejo Hosp. Univ. Juan Canalejo; 🇪🇸 La Coruña, Spain

Hospital San Millan Y San Pedro; 🇪🇸 Logroño, Spain

H. de la Princesa; 🇪🇸 Madrid, Spain

H. Gregorio Marañón; 🇪🇸 Madrid, Spain

H. La Paz; 🇪🇸 Madrid, Spain

Fundación Jimenez Diaz; 🇪🇸 Madrid, Spain

Clinica Rotger; 🇪🇸 Palma de Mallorca, Spain

H. Son Llàtzer; 🇪🇸 Palma de Mallorca, Spain

H. de Donostia; 🇪🇸 San Sebastian, Spain

H. Virgen del Rocío; 🇪🇸 Sevilla, Spain

H. Dr. Peset; 🇪🇸 Valencia, Spain

PO di SS.ma Annunziata; 🇮🇹 Sassari, Italy

Centre Hospitalier Universitaire D'Angers; 🇫🇷 Angers, France

H. Marqués de Valdecilla; 🇪🇸 Santander, Cantabria, Spain

ICO - H. Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Hospital Insular Gran Canaria; 🇪🇸 Las Palmas De Gran Canaria, Las Palmas, Spain

Hospital de Mataró; 🇪🇸 Mataró, Barcelona, Spain

AO S.Camillo Forlanini; 🇮🇹 Roma, Italy

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

CRO di Aviano; 🇮🇹 Aviano, Italy

AO Monaldi; 🇮🇹 Napoli, Italy

Hôpital A. Mignot; 🇫🇷 Le Chesnay, France

Centre Hospitalier de Meaux; 🇫🇷 Meaux, France

Centre Hospitalier de Mulhouse; 🇫🇷 Mulhouse, France

Hôpital Larrey; 🇫🇷 Toulouse, France

Istituti Fisioterapici Ospitalieri; 🇮🇹 Roma, Italy