Combination Chemotherapy Compared With No Treatment Following Surgery in Treating Patients With Non-small Cell Lung Cancer

A LARGE-SCALE TRIAL EVALUATING ADJUVANT CHEMOTHERAPY AFTER CURATIVE RESECTION OF NON-SMALL CELL LUNG CANCER

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if combination chemotherapy given after surgery is more effective than surgery alone for non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy following surgery with that of surgery alone in treating patients who have stage I, stage II, or stage IIIA non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Radiation: radiation therapy; Drug: etoposide; Drug: cisplatin; Drug: vinorelbine tartrate; Drug: vinblastine sulfate; Drug: vindesine

Detailed Description

OBJECTIVES: I. Compare the impact on overall survival of adjuvant cisplatin and either a vinca alkaloid or etoposide (with or without radiotherapy) vs. no adjuvant chemotherapy in patients with completely resected stage I/II/III non-small cell lung cancer. II. Assess the frequency of treatment-related deaths and severe toxic effects. III. Describe the patterns of failure, second malignancies, and toxic effects associated with each treatment regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by participating institution, type of prior surgery, and pathologic stage. Each participating center will determine which combination chemotherapy regimen and which of three cisplatin doses will be given to all patients treated at that center. The treatment group receives cisplatin combined with either vindesine, vinblastine, vinorelbine, or etoposide every 3-4 weeks for 3-4 courses, depending on the dose of cisplatin. The second group receives no adjuvant chemotherapy. Treating institutions determine prior to entering the trial which patients receive adjuvant radiotherapy: none; those with node-positive disease; those with N1 disease only; those with N2 disease only; or those eligible for a randomized radiotherapy trial. For patients in the treatment group, radiotherapy begins 3-4 weeks after the last course. Patients are followed at 6 months, then annually.

PROJECTED ACCRUAL: A maximum of 3,300 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 3300
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1638
    • Getlac
• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • South Eastern Sydney Area Health Service
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 8006
      • Peter Maccallum Cancer Institute
    • Melbourne, Victoria, Australia, 3181
      • Alfred Hospital
    • Melbourne, Victoria, Australia, 3011
      • Western Hospital
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Austria
  • Vienna, Austria, A-1090
    • AKH Vienna
• Belgium
  • Brugge, Belgium, 8000
    • A.Z. St. Jan
  • Edegem, Belgium, B-2650
    • Universitair Ziekenhuis Antwerpen
  • Leuven, Belgium, B-3000
    • U.Z. Gasthuisberg
  • Ronse, Belgium, B-9600
    • AZ Zusters Van Barmhartigheid
  • Zottegem, Belgium, 9620
    • Sint Elizabeth Ziekenhuis
• Brazil
  • Rio De Janeiro, Brazil
    • University of Clementino Fraga
  • Rio de Janeiro, Brazil, Cep 2-0230
    • Instituto Nacional de Cancer
  • Sao Paulo, Brazil, 01509--010
    • Hospital A.C. Camargo
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035--003
      • Porto Alegre Hospital
• Chile
  • Santiago, Chile
    • Clinica Las Nieves
• Colombia
  • Bogota, Colombia
    • Instituto Nacional de Cancerologia
  • Bogota, Colombia
    • Hospital Militar Central
• Czech Republic
  • Prague (Praha), Czech Republic, 162 00
    • Chest Disease Clinic, Charles University
• Egypt
  • Cairo, Egypt
    • National Cancer Institute of Egypt
• Former Yugoslavia
  • Belgrade, Former Yugoslavia, 11000
    • Institute for Lung Diseases
• France
  • Angers, France, 49033
    • Centre Hospitalier Regional et Universitaire d'Angers
  • Angers, France, 49036
    • Centre Paul Papin
  • Armentieres, France, 59427
    • C.H. Armentieres
  • Aulnay Sous Bois, France, 93602
    • Centre Hospital General Robert Ballanger
  • Aurillac, France, 15002
    • C.H. Henri Mondor
  • Bagneux, France, 92220
    • Clinique Hauts De Seine Bagneux
  • Beauvais, France, 60021
    • C.H.G. Beauvais
  • Bobigny, France, 93009
    • Hopital Avicenne
  • Bois Guillaume (Rouen), France, 76235
    • C.M.C. Du Cedre
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Caen, France, 14033
    • CHU de Caen
  • Cannes, France, 06400
    • Centre Du Meridien
  • Chartres, France, 28018
    • Hopital Fontenoy
  • Clamart, France, 92141
    • Hôpital Antoine Béclère
  • Compiegne, France, 60321
    • Centre Hospitalier General
  • Creteil, France, 94010
    • Hôpital Intercommunal de Créteil
  • Dijon, France, 21079
    • Centre de Lute Contre le Cancer,Georges-Francois Leclerc
  • Etampes, France, 91150
    • Hopital D'Etampes
  • Grasse, France, 06130
    • C.H. De Grasse
  • Lagny, France, 77405
    • Centre Hospitalier de Lagny
  • Le Havre, France, 76083
    • C.H.G. Du Havre-Hopital J. Monod
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • Centre Leon Bérard
  • Marseille, France, 13274
    • Assistance Publique Hopitaux de Marseille Hopitaux Sud
  • Mayenne, France, 53013
    • C.H. Nord Mayenne
  • Metz, France, 57070
    • Hopital Clinique Claude Bernard
  • Meudon-La-Foret, France, 92360
    • Centre de Radiologie et de Traitement des Tumeurs
  • Montpellier, France, 34295
    • Hopital Arnaud de Villeneuve
  • Neuilly sur Seine, France, 92200
    • Clinique Hartmann
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75970
    • Hopital Tenon
  • Paris, France, 75248
    • Institut Curie - Section Medicale
  • Paris, France, 75013
    • Institut Mutualiste Montsouris
  • Paris, France, 75014
    • Hospital Saint-Joseph
  • Pau, France, 64000
    • C.H.G. De Pau
  • Poitiers, France, 86021
    • Hopital Jean Bernard
  • Rennes, France, 35033
    • CHU de Pontchaillou
  • Saint-Brieuc, France, 22023
    • Centre Hospitalier de Saint-Brieuc
  • Sarcelles, France, 95250
    • Centre du Rouget
  • Sens, France, 89106
    • C.H. De Sens
  • Strasbourg, France, 67091
    • Hopitaux Universitaire de Strasbourg
  • Troyes, France, 10003
    • C.H.G. Troyes
  • Vandoeuvre-les-Nancy, France, 54511
    • Centre Alexis Vautrin
  • Villejuif, France, F-94805
    • Institut Gustave Roussy
• Greece
  • Athens, Greece, 11527
    • Athens University-Laikon General Hospital
  • Athens, Greece, 10676
    • Evangelismos Hospital
  • Athens, Greece
    • Sotiria Hospital Chest Diseases
  • Athens, Greece, 15126
    • Sismanoglio Hospital
  • Piraeus, Greece, 18537
    • Metaxa's Memorial Cancer Hospital
  • Rio Patras, Greece, GR-26500
    • University of Patras Medical School
  • Thessaloniki, Greece, 57010
    • George Papanicolaou General Hospital
  • Crete
    • Iraklion (Heraklion), Crete, Greece, 71110
      • University Hospital of Heraklion
• Israel
  • Rehovot, Israel, 76100
    • Kaplan Hospital
  • Tel-Aviv, Israel, 62995
    • Tel-Aviv Medical Center
• Italy
  • Milano, Italy, 20141
    • Istituto Europeo Di Oncologia
  • Naples, Italy, 80131
    • Federico II University Medical School
  • Palermo, Italy, 90146
    • Ospedale Cervello
  • Palermo, Italy
    • Ospedale Oncologico M. Ascoli
  • Rimini, Italy, 47037
    • Ospedale Civile Rimini
  • Rome, Italy, 00135
    • Ospedale San Filippo Neri
  • Rome, Italy, 00191
    • Clinica Ars Medica
  • Torino, Italy, 10126
    • Istituto Di Clinica Chirurgica
  • Turin, Italy, 10126
    • Ospedale Molinette
  • Udine, Italy, 33100
    • Università degli Studi di Udine
  • Verona, Italy, 37126
    • Ospedale Di Borgo Trento
• Japan
  • Osaka, Japan, 591
    • National Kinki Central Hospital
• Lithuania
  • Vilnius, Lithuania, 2600
    • Lithuanian Oncology Center
• Macedonia, The Former Yugoslav Republic of
  • Skopje, Macedonia, The Former Yugoslav Republic of, 91000
    • Institute of Radiotherapy and Oncology
• Morocco
  • Rabat, Morocco
    • Institut National D'Oncologie
• Norway
  • Tromso, Norway, N-9037
    • University of Tromso
• Philippines
  • Quezon City Diliman, Philippines, 1100
    • Lung Centre of the Philippines
• Poland
  • Bialystok, Poland, 15276
    • Bialystok Medical School
  • Lodz, Poland, 93509
    • Institute of Oncology
  • Wroclaw, Poland, 50345
    • Department of Children Hematology/Oncology University of Medicine Wroclaw
  • Wroclaw, Poland, 53 439
    • K. Dluski Hospital-Medical Academy
  • Zdunowo, Poland, 20
    • Regional Hospital for Lung Disease
• Portugal
  • Lisbon (Lisboa), Portugal, 1699
    • Hospital Santa Maria
• Slovenia
  • Ljubljana, Slovenia, 61105
    • University of Ljubljana
• South Africa
  • Cape Town, South Africa, 7925
    • Groote Schuur Hospital, Cape Town
  • Johannesburg, South Africa, 2121
    • Sandton Oncology Centre
  • Johannesburg, South Africa
    • Park Lane Oncology Practice
• Spain
  • Barcelona, Spain, 08907
    • Institut Català d'Oncologia - Hospital Duran i Reynals
  • Granada, Spain, 18014
    • Hospital Virgen de las Nieves
  • Valencia, Spain, 46015
    • Hospital Arnau Vilanova
• Sweden
  • Gothenburg (Goteborg), Sweden, S-413 45
    • Sahlgrenska University Hospital
  • Linkoping, Sweden, S-581 85
    • University Hospital of Linkoping
  • Lund, Sweden, S-22185
    • Lund University Hospital
  • Stockholm, Sweden, S-171 76
    • Karolinska Hospital
  • Uppsala, Sweden, S-751 85
    • University Hospital - Uppsala
• Switzerland
  • Basel, Switzerland, CH-4031
    • University Hospital
  • Bellinzona, Switzerland, CH-6500
    • Ospedale San Giovanni
  • Chur, Switzerland, CH-7000
    • Ratisches Kantons und Regionalspital
  • Geneva, Switzerland, CH-1211
    • Hopital Cantonal Universitaire de Geneva
  • Luzern (Lucerne), Switzerland, CH-6000
    • Kantonsspital, Luzern
  • Zurich, Switzerland, CH-8091
    • UniversitaetsSpital
  • Zurich, Switzerland, 8063
    • City Hospital Triemli
• Tunisia
  • Monastir, Tunisia, 5000
    • Hopital Universitaire F. Bourguiba
• United States
  • Florida
    • Atlantis, Florida, United States, 33462
      • Comprehensive Cancer Center at JFK Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histologically documented non-small cell lung cancer Any non-small cell histology eligible Pathologic stage I/II/III disease that is completely resected with microscopically clear margins within 60 days of entry (30 days preferred)

PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: No clear contraindication to chemotherapy No second malignancy except: Nonmelanomatous skin cancer Carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior thoracic radiotherapy Surgery: Complete resection required prior to entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris
• Investigators: Study Chair: Thierry L. Le Chevalier, MD, Gustave Roussy, Cancer Campus, Grand Paris

Publications and helpful links

General Publications

• Hotta K, Matsuo K, Kiura K, Ueoka H, Tanimoto M. Advances in our understanding of postoperative adjuvant chemotherapy in resectable non-small-cell lung cancer. Curr Opin Oncol. 2006 Mar;18(2):144-50. doi: 10.1097/01.cco.0000208787.91947.a2.
• Pignon JP, Tribodet H, Scagliotti GV, et al.: Lung Adjuvant Cisplatin Evaluation (LACE): a pooled analysis of five randomized clinical trials including 4,584 patients. [Abstract] J Clin Oncol 24 (Suppl 18): A-7008, 2006.
• Wakelee HA, Schiller JH, Gandara DR. Current status of adjuvant chemotherapy for stage IB non-small-cell lung cancer: implications for the New Intergroup Trial. Clin Lung Cancer. 2006 Jul;8(1):18-21. doi: 10.3816/CLC.2006.n.028.
• Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria JC; IALT Bio Investigators. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006 Sep 7;355(10):983-91. doi: 10.1056/NEJMoa060570.
• Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. doi: 10.1056/NEJMoa031644.
• Reiman T, Lai R, Veillard AS, Paris E, Soria JC, Rosell R, Taron M, Graziano S, Kratzke R, Seymour L, Shepherd FA, Pignon JP, Seve P. Cross-validation study of class III beta-tubulin as a predictive marker for benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of four randomized trials. Ann Oncol. 2012 Jan;23(1):86-93. doi: 10.1093/annonc/mdr033. Epub 2011 Apr 6.
• Bepler G, Olaussen KA, Vataire AL, Soria JC, Zheng Z, Dunant A, Pignon JP, Schell MJ, Fouret P, Pirker R, Filipits M, Brambilla E. ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis. Am J Pathol. 2011 Jan;178(1):69-78. doi: 10.1016/j.ajpath.2010.11.029. Epub 2010 Dec 23.
• Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Pechoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant Cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. doi: 10.1200/JCO.2009.23.2272. Epub 2009 Nov 23.
• Voortman J, Goto A, Mendiboure J, Sohn JJ, Schetter AJ, Saito M, Dunant A, Pham TC, Petrini I, Lee A, Khan MA, Hainaut P, Pignon JP, Brambilla E, Popper HH, Filipits M, Harris CC, Giaccone G. MicroRNA expression and clinical outcomes in patients treated with adjuvant chemotherapy after complete resection of non-small cell lung carcinoma. Cancer Res. 2010 Nov 1;70(21):8288-98. doi: 10.1158/0008-5472.CAN-10-1348. Epub 2010 Oct 26.
• Filipits M, Pirker R, Dunant A, Lantuejoul S, Schmid K, Huynh A, Haddad V, Andre F, Stahel R, Pignon JP, Soria JC, Popper HH, Le Chevalier T, Brambilla E. Cell cycle regulators and outcome of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer: the International Adjuvant Lung Cancer Trial Biologic Program. J Clin Oncol. 2007 Jul 1;25(19):2735-40. doi: 10.1200/JCO.2006.08.2867.
• Brambilla E, Dunant A, Filipits M, et al.: Prognostic and predictive role of alterations of the P53-bax-bcl2 pathway of apoptosis in the IALT (International Adjuvant Lung Cancer Trial). [Abstract] Lung Cancer 50 (Suppl 2): A-O-021, S10, 2005.
• Le Chevalier T: Results of the Randomized International Adjuvant Lung Cancer Trial (IALT): cisplatin-based chemotherapy (CT) vs no CT in 1867 patients (pts) with resected non-small cell lung cancer (NSCLC). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-6, 2, 2003.

Study record dates

Study Major Dates

• Study Start: February 1, 1995
• Primary Completion (Actual): January 1, 2001

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: March 10, 2004
• First Posted (Estimate): March 11, 2004

Study Record Updates

• Last Update Posted (Estimate): March 28, 2013
• Last Update Submitted That Met QC Criteria: March 26, 2013
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: squamous cell lung cancer; large cell lung cancer; adenocarcinoma of the lung; stage I non-small cell lung cancer; stage II non-small cell lung cancer; adenosquamous cell lung cancer; stage III non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Vinorelbine; Vinblastine; Vindesine
• Other Study ID Numbers: CDR0000065002; FRE-IALT; EU-96010