The purpose of this study is to compare first-line erlotinib followed at progression by
second-line chemotherapy vs. first-line chemotherapy followed at progression by second-line
erlotinib in the treatment of Advanced Non Small Cell Lung Cancer (NSCLC).
- erlotinib taken by mouth daily; and, if disease progression occurs, to be followed by
chemotherapy with cisplatin and gemcitabine at standard doses for 6 cycles
OR
- chemotherapy with cisplatin and gemcitabine given intravenously at standard doses for 6
cycles; and if disease progression occurs to be followed by erlotinib taken by mouth daily
The study is conducted with the partial support of Roche, S. p.A.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- Diagnosis of cytologically or histologically confirmed non-small cell lung cancer
- Metastatic (stage IV) or locally advanced (stage IIIB, with metastasis to
supraclavicular nodes or with pleural effusion).
- Both patients at first diagnosis or those with disease recurrence after former
surgery are eligible.
- At least one target or non-target lesion according to RECIST criteria
- Male or female > 18 years of age (Italy upper age limit 70 years)
- ECOG PS 0 or 1
- Life expectancy of > 3 months
- Neutrophils > 1,500 mm3, platelets > 100,000 mm3, and hemoglobin > 9 g/dL
- Bilirubin level either normal or < 1. 5 x ULN
- AST (SGOT) and ALT (SGPT) < 2. 5 x ULN (< 5 x ULN if liver metastasis are present)
- Serum creatinine < 1. 5 x ULN
- Effective contraception for both, male and female patients if the risk of conception
exists
- Signed written informed consent
Exclusion Criteria:
- Prior exposure to agents directed at the HER axis (e. g. gefitinib, cetuximab,
trastuzumab).
- Prior chemotherapy or therapy with systemic anti-neoplastic therapy (e. g., monoclonal
antibody therapy) for advanced disease. Prior surgery and/or localised irradiation is
permitted. Prior neoadjuvant chemotherapy for operable disease or adjuvant
chemotherapy is permitted if it did not contain gemcitabine and if at least 1 year
elapsed from the end of chemotherapy and the date of relapse.
- Any unstable systemic disease (including active infections, significant
cardiovascular disease or myocardial infarction within the previous year, any
significant hepatic, renal or metabolic disease), metabolic dysfunction, physical
examination finding, or clinical laboratory finding that contraindicates the use of
study medications or render the patient at high risk from treatment complications.
- Any other malignancies within past 5 years (except for adequately treated carcinoma
in situ of the cervix or basal or squamous cell skin cancer or surgically resected
prostate cancer with normal PSA).
- Patients are excluded if they have brain metastasis or spinal cord compression that
has not yet been definitively treated with surgery and/or radiation; previously
diagnosed and treated CNS metastases or spinal cord compression without evidence of
stable disease (clinically stable imaging) for at least 2 months will also cause
patients to be excluded. Patients with asymptomatic CNS metastases and not requiring
steroids to control symptoms can be included, even if on anti-seizure medications.
- HIV positive patients
- Any inflammatory changes of the surface of the eye at baseline
- Patients who cannot take oral medication, who require intravenous alimentation, have
had prior surgical procedures affecting absorption, or have active peptic ulcer
disease.
- Nursing and/or pregnant females
- Known or suspected hypersensitivity to any of the study drugs.
McGill University Cancer Centre, Montreal, Canada
Ospedale San Lazzaro, Alba, Italy
Ospedale Cardinal Massaia, Asti, Italy
C.R.O. Istituto Nazionale Tumori, Aviano, Italy
Azienda Ospedaliera G. Rummo, Unità Operativa di Oncologia Medica, Benevento, Italy
Ospedale Senatore Antonio Perrino, Brindisi, Italy
Ospedale A. Cardarelli, divisione Medicina Interna, Campobasso, Italy
Ospedale Ramazzini, Day Hospital Oncologico, Carpi, Italy
A.O. Ospedale Mater Domini, Oncoematologia Università Magna Grecia, Catanzaro, Italy
Ospedale Mariano Santo, U.O. di Oncologia Medica, Cosenza, Italy
Ospedale S. Corce, Fano, Italy
Azienda Ospedaliera Careggi, Firenze, Italy
Azienda Ospedaliera Morgagni Pierantoni, Forli', Italy
Ospedale Umberto I, U.O. di Oncologia Medica, Frosinone, Italy
Ospedale S. Martino, Genova, Italy
Ospedale Villa Scassi, Genova, Italy
Ospedale S. Maria Goretti, Latina, Italy
A.O. Vito Fazzi, Lecce, Italy
Ospedale C. Poma, Mantova, Italy
Policlinico Universitario G. Martino, Messina, Italy
Casa di Cura IGEA, Milano, Italy
Niguarda Ca' Granda, Milano, Italy
Ospedale L. Sacco, GISCAD Oncologia, Polo Universitario, Milano, Italy
Buon Consiglio Fatebenefratelli, Napoli, Italy
Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B, Napoli, Italy
Ospedale Cardarelli, Napoli, Italy
Second University of Naples, Napoli, Italy
Università Federico II, Cattedra di Oncologia Medica, Napoli, Italy
Divisione di Oncologia Medica, U.S.L.L. 13, Noale, Italy
Ospedale Civile Umbero I, Nocera Inferiore, Italy
Ospedale Civile di Nola, Reparto di Oncologia, Nola, Italy
Istituto Oncologico Veneto, Padova, Italy
Fondazione Salvatore Maugeri, Pavia, Italy
Ospedale S. Salvatore, Pesaro, Italy
Ospedale Guglielmo da Saliceto, Piacenza, Italy
Azienda Ospedaliera S. Carol, Potenza, Italy
Ospedale degli Infermi, U.O. Oncologia Medica, Rimini, Italy
Istituto Regina Elena, Divisione di Oncologia Medica, Roma 00144, Italy
Ospedale S. Giovanni Calibita Fatebenefratelli, UO di Oncologia, Roma, Italy
Azienda Ospedaliera Universitaria Arcispedal, U.O. di Oncologia Clinica, Sant'Anna di Ferrara, Italy
Azienda Ospedaliera Di Busto Arsizio, Saronno, Italy
Azienda Ospedaliera Universitaria Senese, Siena, Italy
Ospedale E. Morelli, Sondalo, Italy
Azienda Sanitaria Locale 14, Verbania, Italy
Ospedale S. Andrea, Vercelli, Italy
ASL Viterbo Ospedale, Belcolle, (vt), Italy
Azienda Sanitaria S. Giuseppe Moscati, Monteforte Irpino, AV, Italy
Tom Baker Cancer Centre, Calgary, Alberta, Canada
University of Alberta Cross Cancer Institute, Edmonton, Alberta, Canada
Istituto Oncologico di Bari, U.O. di Oncologia Medica e Sperimentale, Bari, BA 70126, Italy
BC Cancer Agency Vancouver Island, Victoria, British Columbia, Canada
Università di Chieti, Cattedra di Oncologia Medica, Chieti, CH, Italy
Humanitas Centro Catanese di Oncologia, Catania, CT, Italy
Ospedale di Gaeta, Gaeta, LT 04024, Italy
Ospedale S. Vincenzo di Taormina, Taormina, ME, Italy
Cancer Care Mannitoba, Winnipeg, Manitoba, Canada
QE II Health Sciences Centre, Halifax, Nova Scotia, Canada
Juravinski Cancer Centre, Hamilton, Ontario, Canada
Kingston Regional Cancer Centre, Kingston, Ontario, Canada
Credit Valley Hospital, Mississauga, Ontario, Canada
Durham Regional Cancer Centre, Oshawa, Ontario, Canada
Hôpital Régional de Sudbury Regional Hospital, Sudbury, Ontario, Canada
Mount Sinai Hospital, Toronto, Ontario, Canada
Princess Margaret Hospital, Toronto, Ontario, Canada
Windsor Regional Cancer Centre, Windsor, Ontario, Canada
Azienda Ospedaliera V. Cervello, Palermo, PA, Italy
Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico, Palermo, PA 90146, Italy
Policlinico Universitario P. Giaccone, Palermo, PA 90100, Italy
Azienda Ospedaliera S. Maria degli Angeli, Servizio di Oncologia, Pordenone, PN 33170, Italy
Ospedale di Prato, Prato, PO 59100, Italy
Ospedale Civile di Faenza, Divisione di Oncologia Medica, Faenza, RA 48018, Italy
Ospedale S. Luca, Vallo della Lucania, SA, Italy
Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada
Gridelli C, Ciardiello F, Gallo C, Feld R, Butts C, Gebbia V, Maione P, Morgillo F, Genestreti G, Favaretto A, Leighl N, Wierzbicki R, Cinieri S, Alam Y, Siena S, Tortora G, Felletti R, Riccardi F, Mancuso G, Rossi A, Cantile F, Tsao MS, Saieg M, da Cunha Santos G, Piccirillo MC, Di Maio M, Morabito A, Perrone F. First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. J Clin Oncol. 2012 Aug 20;30(24):3002-11. doi: 10.1200/JCO.2011.41.2056. Epub 2012 Jul 9.