Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer in Complete Remission

A Phase III Trial Comparing High Versus Standard Dose of Prophylactic Cranial Irradiation (PCI) in Limited Small Cell Lung Cancer Complete Responders

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells and prevent the spread of cancer to the brain. It is not yet known if standard-dose radiation therapy is more effective than high-dose radiation therapy in preventing the spread of limited-stage small cell lung cancer cells to the brain.

PURPOSE: This randomized phase III trial is comparing two different regimens of radiation therapy to see how well they work in treating patients with limited-stage small cell lung cancer in complete remission.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Radiation: radiation therapy

Detailed Description

OBJECTIVES:

• Compare high-dose versus standard-dose prophylactic cranial radiotherapy in terms of the incidence of brain metastases and overall and disease free survival at 2 years in patients with limited stage small cell lung cancer in complete remission.
• Evaluate the quality of life and late sequelae in this patient population treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, age (60 and under vs over 60), and interval between the start of induction therapy and date of randomization (90 days or less vs 91-180 days vs more than 180 days). Patients are randomized into one of two treatment arms according to the prophylactic cranial radiotherapy dose.

• Arm I: Patients receive standard-dose prophylactic cranial radiotherapy (10 fractions/12 days).

• Arm II: Patients receive high-dose prophylactic cranial radiotherapy administered over 16 or 24 days based on the choice of their treatment center.

  • 18 fractions/24 days (conventional radiotherapy) OR
  • 24 fractions/16 days (accelerated hyperfractionated radiotherapy) Patients with isolated brain failure may undergo further radiotherapy.

Quality of life is assessed prior to randomization, at 6 months, at 1 year, and then annually thereafter.

Patients are followed at least every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 700 patients will be accrued for this study within 3 years.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Campbelltown, New South Wales, Australia, 2560
      • Cancer Therapy Centre at Campbelltown Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Radiation Oncology Victoria
• Belgium
  • Antwerpen, Belgium, 2020
    • Ziekenhuis Netwerk Antwerpen Middelheim
  • Ghent, Belgium, B-9000
    • Universiteit Gent
  • Haine Saint Paul, Belgium, 7100
    • Hopital de Jolimont
  • Kortrijk, Belgium, B-8500
    • Cazk Groeninghe - Campus Maria's Voorzienigheid
  • Liege, Belgium, B 4000
    • Clinique Saint-Joseph
  • Namur, Belgium, 50000
    • Clinique Sainte Elisabeth
• Brazil
  • Rio de Janeiro
    • Copacabana, Rio de Janeiro, Brazil, CEP 22040-010
      • Instituto Nacional de Câncer
• Chile
  • Santiago, Chile, 10
    • Instituto de Radiomedicina
  • Vina Del Mar, Chile
    • Clinica Renaca - Gocchi
• China
  • Shanghai, China, 200025
    • Rui Jin Hospital
• Colombia
  • Bogota, Colombia
    • Hospital Militar Central
• Cyprus
  • Nicosia, Cyprus, 2006 Strovolos
    • Bank Of Cyprus Oncology Centre
• Czech Republic
  • Brno, Czech Republic, 656 53
    • Masaryk Memorial Cancer Institute
  • Prague, Czech Republic, 128 08
    • First Medical Clinic of Charles University Hospital
• France
  • Ales, France, F-30100
    • Clinique De Rochebelle
  • Amiens, France, 80000
    • Centre de Traitement Hautes - Energies
  • Angers, France, 49036
    • Centre Paul Papin
  • Argenteuil, France, 95107
    • Centre Hospitalier Victor Dupouy
  • Beauvais, France, 60000
    • C.H.G. Beauvais
  • Boucher, France, 33300
    • Polyclinique Bordeaux Nord Aquitaine
  • Caen, France, 14076
    • Centre Regional Francois Baclesse
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Compiegne, France, 60200
    • Centre de Radiotherapie
  • Corbeil, France, 91100
    • Centre Hospitalier Sud Francilien - Site Corbeil
  • Creteil, France, 94010
    • Centre Hospitalier Universitaire Henri Mondor
  • Creteil, France, 94010
    • Hôpital Intercommunal de Créteil
  • Dijon, France, 21079
    • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
  • La Garenne Colombes, France, 92250
    • Centre De Radiotherapie Charlebourg
  • Le Havre, France, 76600
    • Centre Guillaume Le Conquerant
  • Limoges, France, 87042
    • Centre Hospital Regional Universitaire de Limoges
  • Meudon La Foret, France, 92360
    • C.R.T.T.
  • Montbelliard, France, 25200
    • C.H. General De Montbelliard
  • Montpellier, France, 34298
    • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
  • Nantes-Saint Herblain, France, 44805
    • CRLCC Nantes - Atlantique
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Orleans, France, 45067
    • CHR D'Orleans - Hopital de la Source
  • Paris, France, 75005
    • Institut Curie - Section Medicale
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Reims, France, 51056
    • Institut Jean Godinot
  • Rouen, France, 76000
    • Centre Frédéric Joliot
  • Sarcelles, France, 95250
    • Centre du Rouget
  • Sartrouville, France, 78500
    • Centre Hospitalier Prive Des Yvelines
  • Strasbourg, France, 67100
    • Hopitaux Universitaire de Strasbourg
  • Suresnes, France, 92151
    • Centre Médico-Chirurgical Foch
  • Toulon, France, 83800
    • Hopital d'Instruction des Armes Sainte-Anne
  • Vannes, France, 56001
    • Centre d'oncologie Saint-Yves
  • Villejuif, France, F-94805
    • Institut Gustave Roussy
• Germany
  • Essen, Germany, D-45122
    • Universitaetsklinikum Essen
• Greece
  • Athens, Greece, 10676
    • Evaggelismos Hospital
  • Athens, Greece
    • Sotiria Hospital Chest Diseases
  • Heraklion, Greece, 71306
    • Venizelion Gr.
  • Rio Patras, Greece, GR-26500
    • University of Patras Medical School
  • Crete
    • Heraklion, Crete, Greece, 71110
      • University Hospital of Heraklion
• Israel
  • Tel Hashomer, Israel, 52621
    • Chaim Sheba Medical Center
  • Tel-Aviv, Israel, 64239
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Bologna, Italy, I-40139
    • Ospedale Bellaria
  • Pisa, Italy, 56126
    • Università degli studi di Pisa
  • Turin, Italy, 10126
    • Ospedale Ostetrico Ginecologica Sant Anna
• Japan
  • Osaka, Japan, 540-0006
    • Osaka National Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
• Lithuania
  • Vilnius, Lithuania, 08660
    • Institute of Oncology at Vilnius University
• Macedonia, The Former Yugoslav Republic of
  • Skopje, Macedonia, The Former Yugoslav Republic of, 1000
    • Institute of Radiotherapy and Oncology
• Netherlands
  • Amsterdam, Netherlands, 1007 MB
    • Akademisch Ziekenhuis Vrije Universiteit - Medisch Centrum
  • Arnhem, Netherlands, 6815 AD
    • Arnhems Radiotherapeutisch Instituut
  • Nijmegen, Netherlands, 6500 HB
    • Nijmegen Cancer Center at Radboud University Medical Center
  • Rotterdam, Netherlands, 3000 CA
    • University Medical Center Rotterdam at Erasmus Medical Center
• Poland
  • Gdansk, Poland, 80 211
    • Medical University of Gdansk
  • Lodz, Poland, 93509
    • Institute of Oncology
  • Poznan, Poland, 60 569
    • Regional Lung Diseases Hospital
  • Warsaw, Poland, 02 781
    • Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
• Portugal
  • Lisbon, Portugal, 1649-035
    • Hospital Santa Maria
• Romania
  • Cluj-Napoca, Romania, 3400
    • Institutul Oncologic - Universitatea de Medicina
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Oncology and Radiology of Serbia
• South Africa
  • Cape Town, South Africa, 7925
    • Groote Schuur Hospital
• Spain
  • El Palmar, Spain, 30120
    • Hospital Virgen de la Arrixaca
  • Granada, Spain, 18014
    • Hospital Virgen de las Nieves
• Switzerland
  • Lausanne, Switzerland, CH-1011
    • Centre Hospitalier Universitaire Vaudois
• Turkey
  • Istanbul, Turkey, 81190
    • Marmara University Hospital
• United Kingdom
  • Cardiff, United Kingdom, CF4 7XL
    • Velindre Cancer Center at Velinde Hospital
  • Sheffield, United Kingdom, S10 2SJ
    • Cancer Research Centre at Weston Park Hospital
  • England
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital N.H.S. Trust
    • Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE
      • Northern Centre for Cancer Treatment at Newcastle General Hospital
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre at Mount Vernon Hospital
    • Nottingham, England, United Kingdom, NG5 1PB
      • Nottingham City Hospital NHS Trust
    • Wolverhampton, England, United Kingdom, WV10 0QP
      • New Cross Hospital
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Western General Hospital
    • Glasgow, Scotland, United Kingdom, G11 6NT
      • Beatson Oncology Centre
    • Inverness, Scotland, United Kingdom, 1V2 3UJ
      • Raigmore Hospital
  • Wales
    • Gwent, Wales, United Kingdom
      • Nevill Hall Hospital
    • Newport Gwent, Wales, United Kingdom, NP9 2UB
      • Royal Gwent Hospital
• United States
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson Cancer Center at University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically proven limited stage small cell lung cancer
• Complete response to induction therapy (at least on chest x-ray)
• Normal brain CT scan or MRI less than 1 month prior to study
• No metastases (including ipsilateral lung metastases and malignant pleural effusion)

PATIENT CHARACTERISTICS:

Age:

• 70 and under

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No prior cerebrovascular disease

Other:

• No epilepsy requiring permanent oral medication
• No other prior malignancy except skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No concurrent chemotherapy

Endocrine therapy:

• Concurrent steroids allowed

Radiotherapy:

• Concurrent thoracic radiotherapy allowed

Surgery:

• Not specified

Other

• No other concurrent antitumoral agent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Incidence of brain metastases 2 years after randomization

Secondary Outcome Measures

Outcome Measure
Overall survival and disease-free survival 2 years after randomization
Quality of life as assessed by Quality of Life Questionnaire (QLQ)-C30/BN20 before randomization, at 6 and 12 months, and annually thereafter
Treatment late sequelae as assessed by Late Effect of Normal Tissue - Subjective Objective Management Analytic scale, brain CT scan, or MRI before randomization and then annually thereafter

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris
• Collaborators: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Cecile Le Pechoux, MD, Gustave Roussy, Cancer Campus, Grand Paris; Suresh Senan, Free University Medical Center

Publications and helpful links

General Publications

• Le Pechoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A; Prophylactic Cranial Irradiation (PCI) Collaborative Group. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol. 2009 May;10(5):467-74. doi: 10.1016/S1470-2045(09)70101-9. Epub 2009 Apr 20.
• Pechoux CL, Hatton M, Kobierska A, et al.: Randomized trial of standard dose to a higher dose prophylactic cranial irradiation (PCI) in limited-stage small cell cancer (SCLC) complete responders (CR): primary endpoint analysis (PCI99-01, IFCT 99-01, EORTC 22003-08004, RTOG 0212). [Abstract] J Clin Oncol 26 (Suppl 15): A-LBA7514, 2008.
• Le Pechoux C, Laplanche A, Faivre-Finn C, Ciuleanu T, Wanders R, Lerouge D, Keus R, Hatton M, Videtic GM, Senan S, Wolfson A, Jones R, Arriagada R, Quoix E, Dunant A; Prophylactic Cranial Irradiation (PCI) Collaborative Group. Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01). Ann Oncol. 2011 May;22(5):1154-1163. doi: 10.1093/annonc/mdq576. Epub 2010 Dec 7.

Study record dates

Study Major Dates

• Study Start: September 1, 1999
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: April 6, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): March 13, 2014
• Last Update Submitted That Met QC Criteria: March 12, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: limited stage 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; Small Cell Lung Carcinoma
• Other Study ID Numbers: CDR0000067664; FRE-IGR-PCI-99; EU-99051; FRE-IFCT-99.01; FRE-IGR-PCI99-EULINT1; EORTC-22003; EORTC-08004