NCT00446225 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2025-03-05

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression Free-survival

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outcome · POSTED

Objective Response

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outcome · POSTED

Overall Survival

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outcome · POSTED

Molecular Markers Related to EGFR and Study Pathology

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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
intervention Names
Drug: Erlotinib
label
A
type
EXPERIMENTAL
description
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.
intervention Names
Drug: Carboplatin
Drug: Gemcitabin
Drug: Docetaxel
Drug: Cisplatin
label
B
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
A
description
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
name
Erlotinib
other Names
Tarceva
type
DRUG
arm Group Labels
B
description
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.
name
Carboplatin
other Names
Paraplatin
type
DRUG
arm Group Labels
B
description
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.
name
Gemcitabin
other Names
Gemzar
type
DRUG
arm Group Labels
B
description
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.
name
Docetaxel
other Names
Taxotere
type
DRUG
arm Group Labels
B
description
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.
name
Cisplatin
other Names
Platinol
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 174
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

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

secondary Outcomes

description
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.
measure
Objective Response
time Frame
From the date of randomization to the date of last follow up, assessed up to 24 months
description
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.
measure
Overall Survival
time Frame
From the date of randomization to the date of last follow up, assessed up to 24 months
description
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.
measure
Molecular Markers Related to EGFR and Study Pathology
time Frame
At baseline

Full study description

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).

Source references

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.
pmid
22285168
type
RESULT
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.
pmid
26181014
type
DERIVED
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.
pmid
25806291
type
DERIVED
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.
pmid
24493829
type
DERIVED