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

Advanced Non-Small Cell Lung Cancer Clinical Trial

— TORCH  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00349219
• Other study ID #: TORCH
• Secondary ID: 2005-005968-90
• Status: Completed
• Phase: Phase 3
• First received: July 4, 2006
• Last updated: January 14, 2016
• Start date: December 2006
• Est. completion date: June 2012

Study information

• Verified date: January 2016
• Source: National Cancer Institute, Naples
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 760
• Est. completion date: June 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Non-Small Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• erlotinib
erlotinib 150 mg taken orally daily until disease progression
• cisplatin
cisplatin 80 mg/m2 IV day 1 every 3 weeks given in second-line therapy
• gemcitabine
gemcitabine 1200 mg/m2 IV days 1 and 8 every 3 weeks, given in second-line
• cisplatin
cisplatin 80 mg/m2 IV day 1 every 3 weeks for 6 cycles
• gemcitabine
gemcitabine 1200 mg/m2 IV days 1 and 8 every 3 weeks for 6 cycles
• erlotinib
erlotinib 150 mg orally taken daily as second line therapy (after disease progression on chemotherapy)

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	University of Alberta Cross Cancer Institute	Edmonton	Alberta
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	McGill University Cancer Centre	Montreal
Canada	Durham Regional Cancer Centre	Oshawa	Ontario
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Hôpital Régional de Sudbury Regional Hospital	Sudbury	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	BC Cancer Agency Vancouver Island	Victoria	British Columbia
Canada	Windsor Regional Cancer Centre	Windsor	Ontario
Canada	Cancer Care Mannitoba	Winnipeg	Manitoba
Italy	Ospedale San Lazzaro	Alba
Italy	Ospedale Cardinal Massaia	Asti
Italy	C.R.O. Istituto Nazionale Tumori	Aviano
Italy	Istituto Oncologico di Bari, U.O. di Oncologia Medica e Sperimentale	Bari	BA
Italy	ASL Viterbo Ospedale	Belcolle	(vt)
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	Humanitas Centro Catanese di Oncologia	Catania	CT
Italy	A.O. Ospedale Mater Domini, Oncoematologia Università Magna Grecia	Catanzaro
Italy	Università di Chieti, Cattedra di Oncologia Medica	Chieti	CH
Italy	Ospedale Mariano Santo, U.O. di Oncologia Medica	Cosenza
Italy	Ospedale Civile di Faenza, Divisione di Oncologia Medica	Faenza	RA
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 di Gaeta	Gaeta	LT
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	Azienda Sanitaria S. Giuseppe Moscati	Monteforte Irpino	AV
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	Azienda Ospedaliera V. Cervello	Palermo	PA
Italy	Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico	Palermo	PA
Italy	Policlinico Universitario P. Giaccone	Palermo	PA
Italy	Fondazione Salvatore Maugeri	Pavia
Italy	Ospedale S. Salvatore	Pesaro
Italy	Ospedale Guglielmo da Saliceto	Piacenza
Italy	Azienda Ospedaliera S. Maria degli Angeli, Servizio di Oncologia	Pordenone	PN
Italy	Azienda Ospedaliera S. Carol	Potenza
Italy	Ospedale di Prato	Prato	PO
Italy	Ospedale degli Infermi, U.O. Oncologia Medica	Rimini
Italy	Istituto Regina Elena, Divisione di Oncologia Medica	Roma
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	Ospedale S. Vincenzo di Taormina	Taormina	ME
Italy	Ospedale S. Luca	Vallo della Lucania	SA
Italy	Azienda Sanitaria Locale 14	Verbania
Italy	Ospedale S. Andrea	Vercelli

Sponsors (5)

Lead Sponsor	Collaborator
National Cancer Institute, Naples	Princess Margaret Hospital, Canada, San Giuseppe Moscati Hospital, Second University of Naples, University of Alberta

Countries where clinical trial is conducted

Canada,  Italy, 

References & Publications (2)

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, Fa — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival		one year	No
Primary	progression free rate of first-line treatment with erlotinib		after 9 weeks of treatment	Yes
Secondary	toxicity		every 3 weeks during treatment, and every 3 months thereafter	Yes
Secondary	progression-free survival		one year	No
Secondary	quality of life during the first-line therapy		every 3 weeks during first-line therapy	No
Secondary	prognostic biologic indicators		end of study	No
Secondary	resource utilization		every 6 weeks during first-line therapy	No
Secondary	response rate		at 9 and 18 weeks from treatment initiation	No