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

Phase 3
Completed
Conditions
Advanced Non-Small Cell Lung Cancer
Interventions
Registration Number
NCT00349219
Lead Sponsor
National Cancer Institute, Naples
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
760
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1gemcitabineerlotinib followed at progression by gemcitabine and cisplatin
1erlotiniberlotinib followed at progression by gemcitabine and cisplatin
1cisplatinerlotinib followed at progression by gemcitabine and cisplatin
2cisplatincisplatin and gemcitabine chemotherapy for 6 cycles, followed at progression by erlotinib
2gemcitabinecisplatin and gemcitabine chemotherapy for 6 cycles, followed at progression by erlotinib
2erlotinibcisplatin and gemcitabine chemotherapy for 6 cycles, followed at progression by erlotinib
Primary Outcome Measures
NameTimeMethod
overall survivalone year
progression free rate of first-line treatment with erlotinibafter 9 weeks of treatment
Secondary Outcome Measures
NameTimeMethod
toxicityevery 3 weeks during treatment, and every 3 months thereafter
progression-free survivalone year
quality of life during the first-line therapyevery 3 weeks during first-line therapy
prognostic biologic indicatorsend of study
resource utilizationevery 6 weeks during first-line therapy
response rateat 9 and 18 weeks from treatment initiation

Trial Locations

Locations (73)

Kingston Regional Cancer Centre

🇨🇦

Kingston, Ontario, Canada

Ospedale S. Vincenzo di Taormina

🇮🇹

Taormina, ME, Italy

Ospedale Cardinal Massaia

🇮🇹

Asti, Italy

C.R.O. Istituto Nazionale Tumori

🇮🇹

Aviano, Italy

McGill University Cancer Centre

🇨🇦

Montreal, Canada

Credit Valley Hospital

🇨🇦

Mississauga, Ontario, Canada

Mount Sinai Hospital

🇨🇦

Toronto, Ontario, Canada

Azienda Sanitaria S. Giuseppe Moscati

🇮🇹

Monteforte Irpino, AV, Italy

Tom Baker Cancer Centre

🇨🇦

Calgary, Alberta, Canada

Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Istituto Regina Elena, Divisione di Oncologia Medica

🇮🇹

Roma, Italy

Azienda Ospedaliera Morgagni Pierantoni

🇮🇹

Forli', Italy

Istituto Oncologico Veneto

🇮🇹

Padova, Italy

Ospedale S. Andrea

🇮🇹

Vercelli, Italy

Hôpital Régional de Sudbury Regional Hospital

🇨🇦

Sudbury, Ontario, Canada

ASL Viterbo Ospedale

🇮🇹

Belcolle, (vt), Italy

Ospedale S. Martino

🇮🇹

Genova, Italy

Ospedale Villa Scassi

🇮🇹

Genova, Italy

Ospedale S. Maria Goretti

🇮🇹

Latina, Italy

Policlinico Universitario P. Giaccone

🇮🇹

Palermo, PA, Italy

Ospedale di Gaeta

🇮🇹

Gaeta, LT, Italy

Ospedale di Prato

🇮🇹

Prato, PO, Italy

Ospedale San Lazzaro

🇮🇹

Alba, Italy

Ospedale Civile di Faenza, Divisione di Oncologia Medica

🇮🇹

Faenza, RA, Italy

A.O. Ospedale Mater Domini, Oncoematologia Università Magna Grecia

🇮🇹

Catanzaro, Italy

Ospedale Umberto I, U.O. di Oncologia Medica

🇮🇹

Frosinone, Italy

A.O. Vito Fazzi

🇮🇹

Lecce, Italy

Ospedale Mariano Santo, U.O. di Oncologia Medica

🇮🇹

Cosenza, Italy

Azienda Ospedaliera Careggi

🇮🇹

Firenze, Italy

Ospedale C. Poma

🇮🇹

Mantova, Italy

Humanitas Centro Catanese di Oncologia

🇮🇹

Catania, CT, Italy

Ospedale S. Corce

🇮🇹

Fano, Italy

Divisione di Oncologia Medica, U.S.L.L. 13

🇮🇹

Noale, Italy

Policlinico Universitario G. Martino

🇮🇹

Messina, Italy

Casa di Cura IGEA

🇮🇹

Milano, Italy

Istituto Nazionale dei Tumori , Divisione di Oncologia Medica B

🇮🇹

Napoli, Italy

Ospedale Civile Umbero I

🇮🇹

Nocera Inferiore, Italy

Niguarda Ca' Granda

🇮🇹

Milano, Italy

Ospedale L. Sacco, GISCAD Oncologia, Polo Universitario

🇮🇹

Milano, Italy

Buon Consiglio Fatebenefratelli

🇮🇹

Napoli, Italy

Ospedale Cardarelli

🇮🇹

Napoli, Italy

Second University of Naples

🇮🇹

Napoli, Italy

Università Federico II, Cattedra di Oncologia Medica

🇮🇹

Napoli, Italy

Ospedale Civile di Nola, Reparto di Oncologia

🇮🇹

Nola, Italy

Ospedale Guglielmo da Saliceto

🇮🇹

Piacenza, Italy

Azienda Ospedaliera Universitaria Arcispedal, U.O. di Oncologia Clinica

🇮🇹

Sant'Anna di Ferrara, Italy

Azienda Sanitaria Locale 14

🇮🇹

Verbania, Italy

Azienda Ospedaliera S. Carol

🇮🇹

Potenza, Italy

Ospedale S. Giovanni Calibita Fatebenefratelli, UO di Oncologia

🇮🇹

Roma, Italy

Ospedale degli Infermi, U.O. Oncologia Medica

🇮🇹

Rimini, Italy

Azienda Ospedaliera Universitaria Senese

🇮🇹

Siena, Italy

Ospedale E. Morelli

🇮🇹

Sondalo, Italy

Windsor Regional Cancer Centre

🇨🇦

Windsor, Ontario, Canada

BC Cancer Agency Vancouver Island

🇨🇦

Victoria, British Columbia, Canada

Saskatoon Cancer Centre

🇨🇦

Saskatoon, Saskatchewan, Canada

University of Alberta Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Cancer Care Mannitoba

🇨🇦

Winnipeg, Manitoba, Canada

QE II Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

Durham Regional Cancer Centre

🇨🇦

Oshawa, Ontario, Canada

Juravinski Cancer Centre

🇨🇦

Hamilton, Ontario, Canada

Istituto Oncologico di Bari, U.O. di Oncologia Medica e Sperimentale

🇮🇹

Bari, BA, Italy

Università di Chieti, Cattedra di Oncologia Medica

🇮🇹

Chieti, CH, Italy

Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico

🇮🇹

Palermo, PA, Italy

Ospedale S. Luca

🇮🇹

Vallo della Lucania, SA, Italy

Azienda Ospedaliera G. Rummo, Unità Operativa di Oncologia Medica

🇮🇹

Benevento, Italy

Azienda Ospedaliera V. Cervello

🇮🇹

Palermo, PA, Italy

Azienda Ospedaliera S. Maria degli Angeli, Servizio di Oncologia

🇮🇹

Pordenone, PN, Italy

Ospedale Senatore Antonio Perrino

🇮🇹

Brindisi, Italy

Ospedale A. Cardarelli, divisione Medicina Interna

🇮🇹

Campobasso, Italy

Ospedale Ramazzini, Day Hospital Oncologico

🇮🇹

Carpi, Italy

Ospedale S. Salvatore

🇮🇹

Pesaro, Italy

Fondazione Salvatore Maugeri

🇮🇹

Pavia, Italy

Azienda Ospedaliera Di Busto Arsizio

🇮🇹

Saronno, Italy

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