Clinical trial NCT00349219: TORCH: A Study of Tarceva or Chemotherapy for the Treatment of Advanced Non Small Cell Lung Cancer
Official title: An International Randomized Phase III Study of First-line Erlotinib Followed by Second-line Cisplatin + Gemcitabine Versus First-line Cisplatin + Gemcitabine Followed by Second-line Erlotinib in Advanced Non Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Non-Small Cell Lung Cancer
Keywords: first-line
second-line
targeted therapy
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
Collaborators: name: San Giuseppe Moscati Hospital
name: Princess Margaret Hospital, Canada
name: University of Alberta
name: University of Campania Luigi Vanvitelli
First posted: 2006-07-06
Enrollment: 760
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 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).

Detailed description: Chemotherapy for patients affected by advanced NSCLC has demonstrated only modest improvement in survival rates over best supportive care: the prognosis of patients remains poor and the side effects are considerable. Therefore, novel agents are urgently needed for this disease. One way to improve effectiveness of therapies is to use non-chemotherapeutic agents that act on biological targets and cause fewer systemic side effects. Erlotinib(Tarceva)is a biological therapy that in recent clinical trials has shown promise in first- and second-line treatment of advanced NSCLC.

In this trial, patients will be randomized to one of two treatment strategies:

- 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.

Eligibility criteria: 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.

Primary outcomes:
measure: overall survival
timeFrame: one year
measure: progression free rate of first-line treatment with erlotinib
timeFrame: after 9 weeks of treatment
Secondary outcomes:
measure: toxicity
timeFrame: every 3 weeks during treatment, and every 3 months thereafter
measure: progression-free survival
timeFrame: one year
measure: quality of life during the first-line therapy
timeFrame: every 3 weeks during first-line therapy
measure: prognostic biologic indicators
timeFrame: end of study
measure: resource utilization
timeFrame: every 6 weeks during first-line therapy
measure: response rate
timeFrame: at 9 and 18 weeks from treatment initiation
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Cross Cancer Institute
state: Alberta
city: Victoria
country: Canada
facility: BC Cancer Agency Vancouver Island
state: British Columbia
city: Winnipeg
country: Canada
facility: Cancer Care Mannitoba
state: Manitoba
city: Halifax
country: Canada
facility: QE II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston Regional Cancer Centre
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Durham Regional Cancer Centre
state: Ontario
city: Sudbury
country: Canada
facility: Hôpital Régional de Sudbury Regional Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Montreal
country: Canada
facility: McGill University Cancer Centre
city: Belcolle
country: Italy
facility: ASL Viterbo Ospedale
state: (vt)
city: Monteforte Irpino
country: Italy
facility: Azienda Sanitaria S. Giuseppe Moscati
state: AV
city: Bari
country: Italy
facility: Istituto Oncologico di Bari, U.O. di Oncologia Medica e Sperimentale
state: BA
city: Chieti
country: Italy
facility: Università di Chieti, Cattedra di Oncologia Medica
state: CH
city: Catania
country: Italy
facility: Humanitas Centro Catanese di Oncologia
state: CT
city: Gaeta
country: Italy
facility: Ospedale di Gaeta
state: LT
city: Taormina
country: Italy
facility: Ospedale S. Vincenzo di Taormina
state: ME
city: Palermo
country: Italy
facility: Policlinico Universitario P. Giaccone
state: PA
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico
state: PA
city: Palermo
country: Italy
facility: Azienda Ospedaliera V. Cervello
state: PA
city: Pordenone
country: Italy
facility: Azienda Ospedaliera S. Maria degli Angeli, Servizio di Oncologia
state: PN
city: Prato
country: Italy
facility: Ospedale di Prato
state: PO
city: Faenza
country: Italy
facility: Ospedale Civile di Faenza, Divisione di Oncologia Medica
state: RA
city: Vallo della Lucania
country: Italy
facility: Ospedale S. Luca
state: SA
city: Alba
country: Italy
facility: Ospedale San Lazzaro
city: Asti
country: Italy
facility: Ospedale Cardinal Massaia
city: Aviano
country: Italy
facility: C.R.O. Istituto Nazionale Tumori
city: Benevento
country: Italy
facility: Azienda Ospedaliera G. Rummo, Unità Operativa di Oncologia Medica
city: Brindisi
country: Italy
facility: Ospedale Senatore Antonio Perrino
city: Campobasso
country: Italy
facility: Ospedale A. Cardarelli, divisione Medicina Interna
city: Carpi
country: Italy
facility: Ospedale Ramazzini, Day Hospital Oncologico
city: Catanzaro
country: Italy
facility: A.O. Ospedale Mater Domini, Oncoematologia Università Magna Grecia
city: Cosenza
country: Italy
facility: Ospedale Mariano Santo, U.O. di Oncologia Medica
city: Fano
country: Italy
facility: Ospedale S. Corce
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi
city: Forli'
country: Italy
facility: Azienda Ospedaliera Morgagni Pierantoni
city: Frosinone
country: Italy
facility: Ospedale Umberto I, U.O. di Oncologia Medica
city: Genova
country: Italy
facility: Ospedale S. Martino
city: Genova
country: Italy
facility: Ospedale Villa Scassi
city: Latina
country: Italy
facility: Ospedale S. Maria Goretti
city: Lecce
country: Italy
facility: A.O. Vito Fazzi
city: Mantova
country: Italy
facility: Ospedale C. Poma
city: Messina
country: Italy
facility: Policlinico Universitario G. Martino
city: Milano
country: Italy
facility: Casa di Cura IGEA
city: Milano
country: Italy
facility: Niguarda Ca' Granda
city: Milano
country: Italy
facility: Ospedale L. Sacco, GISCAD Oncologia, Polo Universitario
city: Napoli
country: Italy
facility: Buon Consiglio Fatebenefratelli
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B
city: Napoli
country: Italy
facility: Ospedale Cardarelli
city: Napoli
country: Italy
facility: Second University of Naples
city: Napoli
country: Italy
facility: Università Federico II, Cattedra di Oncologia Medica
city: Noale
country: Italy
facility: Divisione di Oncologia Medica, U.S.L.L. 13
city: Nocera Inferiore
country: Italy
facility: Ospedale Civile Umbero I
city: Nola
country: Italy
facility: Ospedale Civile di Nola, Reparto di Oncologia
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: Pesaro
country: Italy
facility: Ospedale S. Salvatore
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto
city: Potenza
country: Italy
facility: Azienda Ospedaliera S. Carol
city: Rimini
country: Italy
facility: Ospedale degli Infermi, U.O. Oncologia Medica
city: Roma
country: Italy
facility: Istituto Regina Elena, Divisione di Oncologia Medica
city: Roma
country: Italy
facility: Ospedale S. Giovanni Calibita Fatebenefratelli, UO di Oncologia
city: Sant'Anna di Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria Arcispedal, U.O. di Oncologia Clinica
city: Saronno
country: Italy
facility: Azienda Ospedaliera Di Busto Arsizio
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
city: Sondalo
country: Italy
facility: Ospedale E. Morelli
city: Verbania
country: Italy
facility: Azienda Sanitaria Locale 14
city: Vercelli
country: Italy
facility: Ospedale S. Andrea
Study officials:
affiliation: S.G. Moscati Hospital, Avellino, Italy
name: Cesare Gridelli, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
name: Charles Butts, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Second University of Naples, Italy; Chair Medical Oncology
name: Fortunato Ciardiello, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Princess Margaret Hospital, Divison of Medical Oncology, Toronto, Ontario, Canada
name: Ronald Feld, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Second University of Naples, Italy; Chair Medical Statistics
name: Ciro Gallo, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute, Naples, Italy; Director Clinical Trials Unit
name: Francesco Perrone, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Di Maio M, Leighl NB, Gallo C, Feld R, Ciardiello F, Butts C, Maione P, Gebbia V, Morgillo F, Wierzbicki R, Favaretto A, Alam Y, Cinieri S, Siena S, Bianco R, Riccardi F, Spatafora M, Ravaioli A, Felletti R, Fregoni V, Genestreti G, Rossi A, Mancuso G, Fasano M, Morabito A, Tsao MS, Signoriello S, Perrone F, Gridelli C. Quality of life analysis of TORCH, a randomized trial testing first-line erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advanced non-small-cell lung cancer. J Thorac Oncol. 2012 Dec;7(12):1830-1844. doi: 10.1097/JTO.0b013e318275b327.
citation: Di Maio M, Gallo C, Leighl NB, Piccirillo MC, Daniele G, Nuzzo F, Gridelli C, Gebbia V, Ciardiello F, De Placido S, Ceribelli A, Favaretto AG, de Matteis A, Feld R, Butts C, Bryce J, Signoriello S, Morabito A, Rocco G, Perrone F. Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol. 2015 Mar 10;33(8):910-5. doi: 10.1200/JCO.2014.57.9334. Epub 2015 Jan 26.