Clinical trial NCT00016211: Radiation Therapy to Prevent Brain Metastases in Patients With Previously Treated Extensive-Stage Small Cell Lung Cancer
Official title: Prophylactic Cranial Irradiation In Extensive Disease Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: extensive stage small cell lung cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiation therapy to the brain may be effective in preventing brain metastases. It is not yet known if radiation therapy is effective following chemotherapy in preventing brain metastases.

PURPOSE: Randomized phase III trial to determine the effectiveness of radiation therapy in preventing brain metastases in patients who have received chemotherapy for extensive-stage small cell lung cancer.

Detailed description: OBJECTIVES:

* Compare the incidence of, and time to, symptomatic brain metastases in patients with previously treated extensive stage small cell lung cancer treated with prophylactic cranial irradiation vs no further therapy.
* Compare the quality of life and survival of these patients.
* Determine the toxicity of this regimen in these patients.
* Determine the health economics associated with this study.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and performance status. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Within 5 weeks after completion of prior chemotherapy, patients undergo prophylactic cranial irradiation once daily for 5-12 days.
* Arm II: Patients receive no further therapy after completion of prior chemotherapy.

Quality of life is assessed at baseline, 6 weeks, every 3 months for 1 year, and then every 6 months thereafter.

Patients are followed at 6 weeks, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 287 patients will be accrued for this study within 3 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Cytologically or histologically confirmed small cell lung cancer

  * Documented extensive disease before the initiation of chemotherapy
* Responsive disease after 4 to 6 courses of initial chemotherapy

  * No more than 5 weeks since completion of prior chemotherapy
* No brain or leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age:

* 18 to 75

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Other:

* No other prior or concurrent malignancy except skin cancer or carcinoma in situ of the cervix
* No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* See Disease Characteristics

Endocrine therapy:

* No concurrent corticosteroids

Radiotherapy:

* No prior radiotherapy to the brain
* No prior radiotherapy to the head and neck

Surgery:

* Not specified

Primary outcomes:
measure: Time to symptomatic brain metastases measured by Logrank at 6 weeks, every 3 months in year 1, and then every 6 months
Secondary outcomes:
measure: Quality of life assessed by EORTC QLQ-C30 and EORTC BN-20 at baseline, 6 weeks, every 3 months in year 1, and then every 6 months
measure: Toxicity assessed by NCI CTC v2.0 during treatment, at 6 weeks, every 3 months in year 1, and then every 6 months
measure: Survival measured by Logrank at 6 weeks, every 3 months in year 1, and then every 6 months
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Middelheim
city: Ghent
country: Belgium
facility: Universiteit Gent
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: Kortrijk
country: Belgium
facility: Cazk Groeninghe - Campus Maria's Voorzienigheid
city: Liege
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Liege
country: Belgium
facility: Clinique Saint-Joseph
city: Nicosia
country: Cyprus
facility: Bank Of Cyprus Oncology Centre
city: Cairo
country: Egypt
facility: National Cancer Institute of Egypt
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Kaposvar
country: Hungary
facility: University of Kaposvar
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Cuneo
country: Italy
facility: Ospedale Santa Croce
city: Genoa (Genova)
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: Parma
country: Italy
facility: Azienda Ospedaliera Di Parma
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Arnhem
country: Netherlands
facility: Arnhems Radiotherapeutisch Instituut
city: Deventer
country: Netherlands
facility: Radiotherapeutisch Instituut-(Riso)
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leeuwarden
country: Netherlands
facility: Radiotherapeutisch Instituut Friesland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Nijmegen Cancer Center at Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: University Medical Center Rotterdam at Erasmus Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia Children's Hospital
city: Tilburg
country: Netherlands
facility: Dr. Bernard Verbeeten Instituut
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Istanbul
country: Turkey
facility: Marmara University Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital
state: England
city: Leeds
country: United Kingdom
facility: Cookridge Hospital at Leeds Teaching Hospital NHS Trust
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital N.H.S. Trust
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust
state: England
city: Newcastle Upon Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend NHS Trust Hospital
state: England
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Western Infirmary
state: Scotland
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Gwent
country: United Kingdom
facility: Nevill Hall Hospital
state: Wales
city: Newport Gwent
country: United Kingdom
facility: Royal Gwent Hospital
state: Wales
Study officials:
affiliation: Free University Medical Center
name: B.J. Slotman, PhD, MD
role: STUDY_CHAIR
affiliation: Free University Medical Center
name: Pieter E. Postmus, MD
role: STUDY_CHAIR
References:
citation: Slotman BJ, Mauer ME, Bottomley A, Faivre-Finn C, Kramer GW, Rankin EM, Snee M, Hatton M, Postmus PE, Collette L, Senan S. Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups. J Clin Oncol. 2009 Jan 1;27(1):78-84. doi: 10.1200/JCO.2008.17.0746. Epub 2008 Dec 1.
citation: Slotman B, Faivre-Finn C, Kramer G, et al.: A randomized trial of prophylactic cranial irradiation (PCI) versus no PCI in extensive disease small cell lung cancer after a response to chemotherapy (EORTC 08993-22993). [Abstract] J Clin Oncol 25 (Suppl 18): A-4, 2s, 2007.
citation: Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S; EORTC Radiation Oncology Group and Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72. doi: 10.1056/NEJMoa071780.
citation: Slotman BJ, Faivre-Finn C, Kramer GWPM, et al.: Prophylactic cranial irradiation (PCI) in extensive stage small cell lung cancer (ES-SCLC) (EORTC 22993-08993). [Abstract] Int J Radiat Oncol Biol Phys 69 (3 Suppl): A-7, S4, 2007.
citation: Bernhardt D, Adeberg S, Bozorgmehr F, Opfermann N, Hoerner-Rieber J, Repka MC, Kappes J, Thomas M, Bischoff H, Herth F, Heussel CP, Debus J, Steins M, Rieken S. Nine-year Experience: Prophylactic Cranial Irradiation in Extensive Disease Small-cell Lung Cancer. Clin Lung Cancer. 2017 Jul;18(4):e267-e271. doi: 10.1016/j.cllc.2016.11.012. Epub 2016 Dec 2.
citation: Slotman BJ, Faivre-Finn C, Kramer GW, Rankin E, Snee M, Hatton M, Postmus PE, Collette L, Musat E, Senan S. [Prophylactic cranial irradiation in patients with extensive disease caused by small-cell lung cancer responsive to chemotherapy: fewer symptomatic brain metastases and improved survival]. Ned Tijdschr Geneeskd. 2008 Apr 26;152(17):1000-4. Dutch.