Clinical trial NCT00637910: Tarceva Italian Lung Optimization tRial
Official title: Optimization of Erlotinib for the Treatment of Patients With Advanced Non Small Cell Lung Cancer: an Italian Randomized Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer (NSCLC)
Keywords: Advanced NSCLC
EGFR
EGFR copy number
Kras mutations
EGRF mutations
Docetaxel
Erlotinib
Polymorphisms
Lead sponsor: Fatebenefratelli and Ophthalmic Hospital
Sponsor class: OTHER
Collaborators: name: Mario Negri Institute for Pharmacological Research
name: Niguarda Hospital
First posted: 2008-03-18
Enrollment: 850
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the superiority of docetaxel in comparison to erlotinib in second line in wild-type EGFR tumour patients.

Detailed description: Erlotinib is registered in all patients affected with NSCLC in second and subsequent lines with a small benefit on Overall Survival. Recent evidence suggest that patients with EGFR mutations have a clear benefit when they are treated with EGFR tyrosine kinase inhibitors, while the role of these drugs in wild-type EGFR patients, that are representing the large majority (about 85-90%), is still unclear and no properly planned trials assessed before this issue. Recently, indirect evidence on subgroup analyses on randomized trial suggest that chemotherapy might be superior to erlotinib in wild-type EGFR patients.

Moreover, several authors do not recommend the use of EGFR determined with immunohistochemistry (IHC) or FISH because they do not reproducibly predict outcome.

For these reasons the protocol was amended in May 2011 in a superiority trial of docetaxel versus erlotinib, while the first version was aimed to assess the interaction with biomarkers.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older
* Histological or cytological confirmation of NSCLC (may be from initial diagnosis of NSCLC or subsequent biopsy). Only patients with available tissue samples may be included in the study
* Absence of EGFR mutations of exons 19 or 21 (randomization)
* Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy
* One prior platinum-based at adequate doses and taxane free regimen
* Measurable (uni-dimensional) disease by RECIST in a lesion not previously irradiated or non-measurable disease
* ECOG-PS 0-2
* ANC greater than 1.5 x 109/L and platelets greater than 100 x 109/L
* Bilirubin level either normal or \<1.5xULN
* AST (SGOT) and ALT (SGPT) \<2.5xULN (≤5 x ULN if liver metastases are present)
* Serum creatinine \<1.5xULN
* Effective contraception for both, male and female pts, if the risk of conception exists
* Recovery from all acute toxicities of prior therapies
* Provision of written informed consent to the analysis of biological markers (registration)
* Provision of written informed consent to enter the randomized part of the study (randomization)

Exclusion Criteria:

* Prior therapy with an experimental agent whose primary mechanism of action is inhibition of EGFR or its associated tyrosine kinase
* Prior chemotherapy with taxanes
* Newly diagnosed CNS metastases that have not yet been treated with surgery and/or radiation. Pts with previously diagnosed and treated CNS metastases or spinal cord compression may be considered if they have evidence of clinically SD (no steroid therapy or steroid dose being tapered) for at least 28 daysLess than 14 days since completion of prior radiotherapy or persistence of any radiotherapy related toxicity
* Any unresolved chronic toxicity from previous anticancer therapy that, in the opinion of the investigator, makes it inappropriate for the patient to be enrolled in the study Known severe hypersensitivity to erlotinib or any of the excipients of this product
* Known hypersensitivity to docetaxel, polysorbate 80 or other drugs formulated with polysorbate 80, or any of the excipients of docetaxel
* Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
* Unable to swallow tablets
* Any evidence of clinically active interstitial lung disease (patients with chronic, stable, radiographic changes who are asymptomatic or patients with uncomplicated progressive lymphangitic carcinomatosis need not be excluded)
* As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
* As judged by the investigator, any inflammatory changes of the surface of the eye
* Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

Primary outcomes:
measure: Overall Survival
timeFrame: 12 months after the last patient is randomized
Secondary outcomes:
measure: Progression Free Survival
timeFrame: with 4 years and 12 months after the last patient is randomized
measure: Response assessed with RECIST criteria
timeFrame: within 4 years
measure: Quality of Life assessed with QLQ-C30 and QLQ-LC13 questionnaires
timeFrame: within 4 years
measure: Toxicity, graded according to the NCI-CTAE version 3.0
timeFrame: within 4 years
measure: Frequency and nature of serious adverse reactions
timeFrame: within 4 years
measure: Premature withdrawals
timeFrame: within 4 years
Other outcomes:
Locations:
city: Sciacca
country: Italy
facility: Ospedale Civili Riuniti Giovanni Paolo II
state: Agrigento
city: Fabriano
country: Italy
facility: Fabriano Hospital
state: Ancona
city: Torrette
country: Italy
facility: Ospedali Riuniti Umberto I - Lancisi - Salesi
state: Ancona
city: Ariano Irpino
country: Italy
facility: Oncologia A.S.L. AV1
state: Avellino
city: Alzano Lombardo
country: Italy
facility: Pesenti-Fenaroli Hospital
state: Bergamo
city: Vipiteno
country: Italy
facility: Ospedale di Vipiteno
state: Bolzano
city: Brescia
country: Italy
facility: Oncologia Medica Azienda Spedali Civili
state: BS
city: Brescia
country: Italy
facility: Pneumologia Azienda Spedali Civili
state: BS
city: Bolzano
country: Italy
facility: Ospedale centrale di Bolzano
state: BZ
city: Monserrato
country: Italy
facility: Policlinico Universitario di Monserrato
state: Cagliari
city: Iglesias
country: Italy
facility: Ospedale Santa Barbara
state: Carbonia Iglesias
city: Lanciano
country: Italy
facility: Renzetti Hospital
state: Chieti
city: Caltanissetta
country: Italy
facility: Ospedale S. Elia
state: CL
city: Paola
country: Italy
facility: San Francesco Hospital
state: Cosenza
city: Saluzzo
country: Italy
facility: Ospedale Civile di Saluzzo Savigliano
state: Cuneo
city: Empoli
country: Italy
facility: Istituto Toscano Tumori Ospedale S. Giuseppe Antica Sede
state: Firenze
city: Monfalcone
country: Italy
facility: Monfalcone Hospital
state: Gorizia
city: Casarano
country: Italy
facility: Ospedale Civile Ferrari
state: Lecce
city: Casalpusterlengo
country: Italy
facility: Ospedale Civile di Casalpusterlengo
state: Lodi
city: Latina
country: Italy
facility: Ospedale S. Maria Goretti
state: LT
city: San Severino Marche
country: Italy
facility: B. Eustachio Hospital
state: Macerata
city: Taormina
country: Italy
facility: San Vincenzo Hospital
state: Messina
city: Gorgonzola
country: Italy
facility: Azienda Ospedaliera Melegnano- P.O. Gorgonzola
state: Milano
city: Legnano
country: Italy
facility: Legnano Hospital
state: Milano
city: Magenta
country: Italy
facility: Ospedale Civile di Legnano -Presidio di Magenta
state: Milano
city: Monza
country: Italy
facility: San Gerardo Hospital
state: Milano
city: Rho
country: Italy
facility: Rho Hospital - Azienda Ospedaliera Salvini-Garbagnate
state: Milano
city: San Donato Milanese
country: Italy
facility: Policlinico San Donato
state: Milano
city: Sesto San Giovanni
country: Italy
facility: IRCCS Multimedica
state: Milano
city: Vimercate
country: Italy
facility: Ospedale Civile di Vimercate
state: Milano
city: Vizzolo Predabissi
country: Italy
facility: Vizzolo Predabissi Hospital
state: Milano
city: Gragnano
country: Italy
facility: San Leonardo Hospital
state: Napoli
city: Vigevano
country: Italy
facility: Ospedale Civile Vigevano
state: Pavia
city: Palermo
country: Italy
facility: Policlinico Universitario Palermo
state: PA
city: Penne
country: Italy
facility: San Massimo Hospital
state: Pescara
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico
state: Pordenone
city: Lugo
country: Italy
facility: Umberto I Hospital
state: Ravenna
city: Siderno
country: Italy
facility: Ospedale Civile di Siderno - ASL n°9 Locri
state: Reggio Calabria
city: Correggio
country: Italy
facility: S. Sebastiano Hospital
state: Reggio Emilia
city: Scandiano
country: Italy
facility: Ospedale di Scandiano
state: Reggio Emilia
city: Tivoli
country: Italy
facility: S. Giovanni Evangelista Hospital
state: Roma
city: Nocera Inferiore
country: Italy
facility: ASL SA1 -P.O. Umberto I
state: Salerno
city: Vallo della Lucania
country: Italy
facility: Presidio Ospedaliero San Luca
state: Salerno
city: Montepulciano
country: Italy
facility: Ospedale Valdichiana "Nottola"
state: Siena
city: Poggibonsi
country: Italy
facility: Ospedale Valdelsa "Campostaggia"
state: Siena
city: Terni
country: Italy
facility: Ospedale di Terni
state: TR
city: Castellanza
country: Italy
facility: Multimedia Santa Maria
state: Varese
city: Saronno
country: Italy
facility: Azienda Ospedaliera Busto Arsizio
state: Varese
city: Mestre
country: Italy
facility: Umberto I Hospital
state: Venezia
city: Legnago
country: Italy
facility: Ospedale Mater Salutis
state: Verona
city: Verona
country: Italy
facility: Ospedale Policlinico G.B. Rossi
state: VR
city: Agrigento
country: Italy
facility: S. Giovanni di Dio Hospital
city: Arezzo
country: Italy
facility: Ospedale San Donato
city: Bari
country: Italy
facility: Azienda Ospedaliera Universitaria Consorziale Policlinico
city: Benevento
country: Italy
facility: Fatebenefratelli Hospital
city: Benevento
country: Italy
facility: G. Rummo Hospital
city: Bergamo
country: Italy
facility: Ospedali Riuniti
city: Cagliari
country: Italy
facility: Armando Businco Oncological Hospital
city: Campobasso
country: Italy
facility: Presidio Ospedaliero Cardarelli ASL 3
city: Como
country: Italy
facility: Sant'Anna Hospital
city: Cosenza
country: Italy
facility: Mariano Santo Hospital
city: Crema
country: Italy
facility: Ospedale Maggiore di Crema
city: Cuneo
country: Italy
facility: S. Croce e Carle Hospital
city: Ferrara
country: Italy
facility: A.O.U. S. Anna
city: Firenze
country: Italy
facility: A.O.U. Careggi
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Genova
country: Italy
facility: A.O. San Martino
city: Genova
country: Italy
facility: Galliera Hospital
city: Isernia
country: Italy
facility: F. Veneziale Hospital
city: Lecco
country: Italy
facility: Azienda Ospedaliera di Lecco
city: Milano
country: Italy
facility: Fatebenefratelli and Ophthalmic Hospital
city: Milano
country: Italy
facility: Fondazione Ospedale Maggiore Policlinico - Mangiagalli e Regina Elena
city: Milano
country: Italy
facility: San Paolo Hospital
city: Milano
country: Italy
facility: San Carlo Borromeo Hospital
city: Milano
country: Italy
facility: Azienda Ospedaliera Luigi Sacco Polo Universitario
city: Napoli
country: Italy
facility: A.O. Monaldi
city: Napoli
country: Italy
facility: Cardarelli Hospital
city: Napoli
country: Italy
facility: D. Cotugno Hospital
city: Napoli
country: Italy
facility: San Gennaro Hospital - ASL NA 1
city: Novara
country: Italy
facility: Ospedale Maggiore della Carità
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Presidio "Paolo Giaccone"
city: Palermo
country: Italy
facility: Presidio Ospedaliero "M. Ascoli" ARNAS Civico
city: Palermo
country: Italy
facility: Centro Oncologico "La Maddalena"
city: Perugia
country: Italy
facility: S. Maria della Misericordia Hospital
city: Piacenza
country: Italy
facility: Piacenza Hospital
city: Pordenone
country: Italy
facility: S. Maria degli Angeli Hospital
city: Ravenna
country: Italy
facility: Ospedale Civile Santa Maria delle Croci
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova
city: Roma
country: Italy
facility: Ospedale San Pietro Fatebenefratelli
city: Roma
country: Italy
facility: Pneumologia Oncologica II-San Camillo Forlanini Hospital
city: Roma
country: Italy
facility: Oncologia Medica-San Camillo Forlanini Hopsital
city: Roma
country: Italy
facility: Università Campus Bio-Medico
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Roma
country: Italy
facility: S. Giovanni - Addolorata Hospital
city: Salerno
country: Italy
facility: Azienda Ospedaliera S. Giovanni di Dio e Ruggi d'Aragona
city: Sassari
country: Italy
facility: Ospedale Civile SS. Annunziata
city: Sassari
country: Italy
facility: Universita' di Sassari Oncologia Medica
city: Sondrio
country: Italy
facility: Ospedale Morelli
city: Sondrio
country: Italy
facility: Sondrio Hospital-Azienda Ospedaliera Valtellina e Valchiavenna
city: Torino
country: Italy
facility: A.O.U. San Giovanni Battista Molinette
city: Varese
country: Italy
facility: Ospedale di Circolo
city: Venezia
country: Italy
facility: SS. Giovanni e Paolo Hospital
city: Vicenza
country: Italy
facility: San Bartolo Hospital
city: Viterbo
country: Italy
facility: Belcolle Hospital
Study officials:
affiliation: Fatebenefratelli and Ophthalmic Hospital
name: Alberto Scanni, MD
role: PRINCIPAL_INVESTIGATOR
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