TORCH: A Study of Tarceva or Chemotherapy for the Treatment of Advanced Non Small Cell Lung Cancer

Condition(s) targeted: Advanced Non-Small Cell Lung Cancer

Intervention: erlotinib (Drug); cisplatin (Drug); gemcitabine (Drug); cisplatin (Drug); gemcitabine (Drug); erlotinib (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: National Cancer Institute, Naples

Official(s) and/or principal investigator(s):
Cesare Gridelli, M.D., Principal Investigator, Affiliation: S.G. Moscati Hospital, Avellino, Italy
Charles Butts, M.D., Principal Investigator, Affiliation: University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada
Fortunato Ciardiello, M.D., Ph.D., Principal Investigator, Affiliation: Second University of Naples, Italy; Chair Medical Oncology
Ronald Feld, M.D., Principal Investigator, Affiliation: Princess Margaret Hospital, Divison of Medical Oncology, Toronto, Ontario, Canada
Ciro Gallo, M.D., Ph.D., Principal Investigator, Affiliation: Second University of Naples, Italy; Chair Medical Statistics
Francesco Perrone, M.D., Ph.D., Principal Investigator, Affiliation: National Cancer Institute, Naples, Italy; Director Clinical Trials Unit

Overall contact:
Francesco Perrone, M.D., Ph.D., Phone: +39 081 5903571, Ext: 571, Email: francesco.perrone@uosc.fondazionepascale.it

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).

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 design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome:

overall survival

progression free rate of first-line treatment with erlotinib

Secondary outcome:

toxicity

progression-free survival

quality of life during the first-line therapy

prognostic biologic indicators

resource utilization

response rate

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Francesco Perrone, M.D., Ph.D., Phone: +39 081 5903571, Ext: 571, Email: francesco.perrone@uosc.fondazionepascale.it

McGill University Cancer Centre, Montreal, Canada; Recruiting

Second University of Naples, Napoli, Italy; Recruiting

Azienda Ospedaliera Universitaria Senese, Siena, Italy; Recruiting

Ospedale E. Morelli, Sondalo, Italy; Recruiting

Divisione di Oncologia Medica, U.S.L.L. 13, .Noale, Italy; Recruiting

Ospedale degli Infermi, U.O. Oncologia Medica, Rimini, Italy; Recruiting

Ospedale Mariano Santo, U.O. di Oncologia Medica, Cosenza, Italy; Recruiting

Ospedale Villa Scassi, Genova, Italy; Recruiting

Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B, Napoli, Italy; Recruiting

Azienda Ospedaliera Di Busto Arsizio, Saronno, Italy; Recruiting

Ospedale Cardinal Massaia, Asti, Italy; Recruiting

Ospedale S. Salvatore, Pesaro, Italy; Recruiting

C.R.O. Istituto Nazionale Tumori, Aviano, Italy; Recruiting

Istituto Oncologico Veneto, Padova, Italy; Recruiting

Ospeale SS. Benedetto e Geltrude, Cuggiono, Italy; Recruiting

Casa di Cura IGEA, Milano, Italy; Recruiting

Buon Consiglio Fatebenefratelli, Napoli, Italy; Recruiting

Niguarda Ca' Granda, Milano, Italy; Recruiting

Ospedale S. Martino, Genova, Italy; Recruiting

Ospedale Civile Umbero I, Nocera Inferiore, Italy; Recruiting

Ospedale S. Corce, Fano, Italy; Recruiting

Ospedale S. Gerardo, Monza, Italy; Recruiting

Ospedale Guglielmo da Saliceto, Piacenza, Italy; Recruiting

A.O. Ospedale Mater Domini, Oncoematologia Università Magna Grecia, Catanzaro, Italy; Recruiting

Ospedale Civile di Nola, Reparto di Oncologia, Nola, Italy; Recruiting

Ospedale L. Sacco, GISCAD Oncologia, Polo Universitario, Milano, Italy; Recruiting

Azienda Ospedaliera G. Rummo, Unità Operativa di Oncologia Medica, Benevento, Italy; Recruiting

Ospedale A. Cardarelli, divisione Medicina Interna, Campobasso, Italy; Recruiting

Ospedale S. Giovanni Calibita Fatebenefratelli, UO di Oncologia, Roma, Italy; Recruiting

Ospedale Ramazzini, Day Hospital Oncologico, Carpi, Italy; Recruiting

Azienda Ospedaliera Universitaria Arcispedal, U.O. di Oncologia Clinica, Sant'Anna di Ferrara, Italy; Recruiting

Presidio Ospedaliero Cavalier Raffaele Apicella, Oncologia, Pollena, Italy; Recruiting

Ospedale Umberto I, U.O. di Oncologia Medica, Frosinone, Italy; Recruiting

Fondazione Salvatore Maugeri, Pavia, Italy; Recruiting

Ospedale Maggiore, Trieste, Italy; Recruiting

Azienda Ospedaliera Morgagni Pierantoni, Forli', Italy; Recruiting

Università Federico II, Cattedra di Oncologia Medica, Napoli, Italy; Recruiting

Azienda Ospedaliera S. Carol, Potenza, Italy; Recruiting

a.S.L. AV/1, Ariano Irpino, Italy; Recruiting

Ospedale Cardarelli, Napoli, Italy; Recruiting

Azienda Ospedaliera Desenzano del Garda, Manerbio, Italy; Recruiting

Ospedale S. Maria Goretti, Latina, Italy; Recruiting

Ospedale San Lazzaro, Alba, Italy; Recruiting

Ospedale C. Poma, Mantova, Italy; Recruiting

Azienda Sanitaria Locale 14, Verbania, Italy; Recruiting

Ospedale Senatore Antonio Perrino, Brindisi, Italy; Recruiting

Azienda Ospedaliera Careggi, Firenze, Italy; Recruiting

Ospedale S. Maria della Grazie, Pozzuoli, Italy; Recruiting

Istituto Regina Elena, Divisione di Oncologia Medica, Roma 00144, Italy; Recruiting

ASL Viterbo Ospedale, Belcolle, (VT), Italy; Recruiting

Azienda Sanitaria S. Giuseppe Moscati, Monteforte Irpino, AV, Italy; Recruiting

University of Alberta Cross Cancer Institute, Edmonton, Alberta, Canada; Recruiting

Tom Baker Cancer Centre, Calgary, Alberta, Canada; Recruiting

Istituto Oncologico di Bari, U.O. di Oncologia Medica e Sperimentale, Bari, BA 70126, Italy; Recruiting

Ospedale Fatebenefratelli, U.O. di Oncologia, Benevento, BN 82100, Italy; Recruiting

BC Cancer Agency Vancouver Island, Victoria, British Columbia, Canada; Not yet recruiting

Università di Chieti, Cattedra di Oncologia Medica, Chieti, CH, Italy; Recruiting

Humanitas Centro Catanese di Oncologia, Catania, CT, Italy; Recruiting

IRCCS Casa Solllievo della Sofferenza, San Giovanni Rotondo, FG, Italy; Recruiting

Ospedale di Gaeta, Gaeta, LT 04024, Italy; Recruiting

Ospedale S. Vincenzo di Taormina, Taormina, ME, Italy; Recruiting

Cancer Care Mannitoba, Winnipeg, Manitoba, Canada; Recruiting

Dr. H. Bliss Murphy Cancer Centre, St. John's, Newfoundland and Labrador, Canada; Not yet recruiting

QE II Health Sciences Centre, Halifax, Nova Scotia, Canada; Not yet recruiting

Princess Margaret Hospital, Toronto, Ontario, Canada; Recruiting

Algoma Regional Cancer Program, Sault Ste Marie, Ontario, Canada; Not yet recruiting

Juravinski Cancer Centre, Hamilton, Ontario, Canada; Recruiting

Toronto Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada; Not yet recruiting

Kingston Regional Cancer Centre, Kingston, Ontario, Canada; Recruiting

Durham Regional Cancer Centre, Oshawa, Ontario, Canada; Not yet recruiting

Hôpital Régional de Sudbury Regional Hospital, Sudbury, Ontario, Canada; Recruiting

Mount Sinai Hospital, Toronto, Ontario, Canada; Not yet recruiting

Windsor Regional Cancer Centre, Windsor, Ontario, Canada; Recruiting

Credit Valley Hospital, Mississauga, Ontario, Canada; Recruiting

Policlinico Giaccone, Palermo, PA 90127, Italy; Recruiting

Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico, Palermo, PA 90146, Italy; Recruiting

Policlinico Universitario P. Giaccone, Palermo, PA 90100, Italy; Recruiting

Azienda Ospedaliera V. Cervello, Palermo, PA, Italy; Recruiting

Ospedale Buccheri La Ferla - Fatebenefratelli, Palermo, PA, Italy; Recruiting

Azienda Ospedaliera S. Maria degli Angeli, Servizio di Oncologia, Pordenone, PN 33170, Italy; Recruiting

Ospedale di Prato, Prato, PO 59100, Italy; Recruiting

Ospedale Civile di Faenza, Divisione di Oncologia Medica, Faenza, RA 48018, Italy; Recruiting

Ospedale S. Luca, Vallo della Lucania, SA, Italy; Recruiting

Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada; Recruiting

Starting date: December 2006
Ending date: September 2010
Last updated: September 28, 2009