Clinical trial NCT00002623: Chemotherapy Followed by Surgery or Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer
Official title: RANDOMIZED TRIAL OF SURGERY VERSUS RADIOTHERAPY IN PATIENTS WITH STAGE IIIa NON-SMALL CELL LUNG CANCER AFTER A RESPONSE TO INDUCTION-CHEMOTHERAPY
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: squamous cell lung cancer
large cell lung cancer
stage IIIA non-small cell lung cancer
adenocarcinoma of the lung
adenosquamous cell lung cancer
bronchoalveolar cell lung cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 640
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it can be removed during surgery. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether chemotherapy followed by surgery with or without radiation therapy is more effective than chemotherapy followed by radiation therapy alone in treating non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by surgery with or without radiation therapy to that of chemotherapy followed by radiation therapy alone in treating patients who have stage III non-small cell lung cancer.

Detailed description: OBJECTIVES:

* Compare the overall survival of patients with stage IIIA non-small cell lung cancer treated with surgery with or without radiotherapy versus radiotherapy alone after achieving a response to a neoadjuvant chemotherapy regimen containing cisplatin or carboplatin.
* Compare the progression-free survival of patients treated with these regimens.
* Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, response to induction chemotherapy (complete vs partial vs minor), and histological subtype (squamous vs nonsquamous).

All patients receive 3 courses of induction combination chemotherapy comprising cisplatin or carboplatin in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response (or minor response if disease has become resectable) are randomized to 1 of 2 treatment arms.

* Arm I: Within 6 weeks of randomization, patients undergo radical lobectomy or pneumonectomy plus dissection of the hilar and mediastinal lymph nodes.

Patients with positive resection margins of at least 1 cm and/or positive mediastinal nodes undergo radiotherapy 5 days a week for 5.5 weeks.

Patients with postresection subclinical/microscopic disease with negative tumor margins undergo radiotherapy 5 days a week for 4-4.5 weeks.

* Arm II: Within 6 weeks of randomization, patients undergo primary radiotherapy. Patients with subclinical/microscopic disease with negative tumor margins undergo radiotherapy 5 days a week for 4-4.5 weeks.

Patients with gross tumor volume and tumor margins at least 1 cm undergo radiotherapy 5 days a week for 6 weeks.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 640 patients will be accrued for this study within 8 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically proven primary unresectable non-small cell lung cancer (NSCLC) by mediastinoscopy, mediastinotomy, thoracotomy, video-assisted thoracic surgery, or needle biopsy

  * Stage IIIA (N2) disease by chest CT scan
  * Any histologic subtype allowed
* At least 1 unidimensionally or bidimensionally measurable target lesion on chest CT scan
* No N3 or metastatic disease by physical exam, CT scan of thorax, bone scan, and CT scan or ultrasound of liver and adrenals
* No pre-existing pleural or pericardial effusion
* No symptomatic CNS involvement

PATIENT CHARACTERISTICS:

Age:

* Over 18

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Cardiovascular:

* No superior vena cava syndrome

Pulmonary:

* No diffuse interstitial pulmonary fibrosis

Other:

* No prior melanoma, breast cancer, or hypernephroma
* No other primary malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
* No grade 2 or greater pre-existing motor or sensory neurotoxicity
* No active uncontrolled infection requiring IV antibiotics
* Must be physically and mentally fit for study therapy
* No psychological, familial, sociological, or geographical condition that would preclude study compliance
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy for NSCLC

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy for NSCLC

Surgery:

* No prior surgery for NSCLC

Other:

* No other prior therapy for NSCLC

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: Algemeen Ziekenhuis Middelheim
city: Brugge
country: Belgium
facility: A.Z. St. Jan
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Haine Saint Paul
country: Belgium
facility: Hopital de Jolimont
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Mons
country: Belgium
facility: CHR - Clinique Saint Joseph - Hopital de Warqueguies
city: Mont-Godinne Yvoir
country: Belgium
facility: Clinique Universitaire De Mont-Godinne
city: Roesclare
country: Belgium
facility: Stedelijk Ziekenhuis
city: Vandoeuvre-les-Nancy
country: France
facility: Academisch Ziekenhuis Utrecht
city: Genoa (Genova)
country: Italy
facility: Istituto Nazionale per la Ricerca sul Cancro
city: 's-Hertogenbosch
country: Netherlands
facility: Groot Ziekengasthuis 's-Hertogenbosch
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoekhuis
city: Arnhem
country: Netherlands
facility: Arnhems Radiotherapeutisch Instituut
city: Harderwijk
country: Netherlands
facility: Ziekenhuis St Jansdal
city: Heerlen
country: Netherlands
facility: Atrium Medical Centre
city: Helmond
country: Netherlands
facility: Elkerliek Ziekenhuis
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Roosendaal
country: Netherlands
facility: Saint Franciscus Ziekenhuis
city: Rotterdam
country: Netherlands
facility: University Hospital - Rotterdam Dijkzigt
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Tilburg
country: Netherlands
facility: Twee Steden Ziekenhuis Vestiging Tilburg
city: Utrecht
country: Netherlands
facility: Diakonessenhuis Utrecht
city: Zwolle
country: Netherlands
facility: Sophia Ziekehuis
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: England
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
state: Northern Ireland
Study officials:
affiliation: University Medical Center Rotterdam at Erasmus Medical Center
name: Ted A.W. Splinter, MD
role: STUDY_CHAIR
References:
citation: Van Meerbeeck JP, De Pauw R, Tournoy K. What is the optimal treatment of stage IIIA-N2 non-small-cell lung cancer after EORTC 08941? Expert Rev Anticancer Ther. 2008 Feb;8(2):199-206. doi: 10.1586/14737140.8.2.199.
citation: van Meerbeeck JP, Kramer GW, Van Schil PE, Legrand C, Smit EF, Schramel F, Tjan-Heijnen VC, Biesma B, Debruyne C, van Zandwijk N, Splinter TA, Giaccone G; European Organisation for Research and Treatment of Cancer-Lung Cancer Group. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst. 2007 Mar 21;99(6):442-50. doi: 10.1093/jnci/djk093.
citation: Kramer GW, Legrand CL, van Schil P, Uitterhoeve L, Smit EF, Schramel F, Biesma B, Tjan-Heijnen V, van Zandwijk N, Splinter T, Giaccone G, van Meerbeeck JP; EORTC-Lung Cancer Group. Quality assurance of thoracic radiotherapy in EORTC 08941: a randomised trial of surgery versus thoracic radiotherapy in patients with stage IIIA non-small-cell lung cancer (NSCLC) after response to induction chemotherapy. Eur J Cancer. 2006 Jul;42(10):1391-8. doi: 10.1016/j.ejca.2006.01.052.
citation: Van Meerbeeck JP, Kramer GW, Legrand C, et al.: Does downstaging in patients (pts) with IIIA-N2 non-small cell lung cancer (NSCLC) and a response to induction chemotherapy (ICT) influence outcome with surgery (S) or radiotherapy (RT)? An exploratory analysis of EORTC 08941. [Abstract] J Clin Oncol 24 (Suppl 18): A-7047, 375s, 2006.
citation: Van Meerbeeck JP, Kramer G, Van Schil PE, et al.: A randomized trial of radical surgery (S) versus thoracic radiotherapy (TRT) in patients (pts) with stage IIIA-N2 non-small cell lung cancer (NSCLC) after response to induction chemotherapy (ICT) (EORTC 08941). [Abstract] J Clin Oncol 23 (Suppl 16): A-LBA7015, 624s, 2005.
citation: Van Schil P, Van Meerbeeck J, Kramer G, Splinter T, Legrand C, Giaccone G, Manegold C, van Zandwijk N. Morbidity and mortality in the surgery arm of EORTC 08941 trial. Eur Respir J. 2005 Aug;26(2):192-7. doi: 10.1183/09031936.05.00127204.
citation: van Meerbeeck JP, Kramer GWPM, van Schil PEY, et al.: Induction chemotherapy (CT) in stage IIIA-N2 non-small cell lung cancer (NSCLC):an analysis of different regimens used in EORTC 08941. [Abstract] Lung Cancer 41 (Suppl 2): A-O-273, S79, 2003.
citation: van Schil PE, van Meerbeeck JP, Kramer G, et al.: Surgery after induction chemotherapy: morbidity and mortality in the first 100 patients of the surgery arm of EORTC 08941 trial. [Abstract] Lung Cancer 41 (Suppl 2): A-O-147, S45, 2003.
citation: Splinter TA, van Schil PE, Kramer GW, van Meerbeeck J, Gregor A, Rocmans P, Kirkpatrick A. Randomized trial of surgery versus radiotherapy in patients with stage IIIA (N2) non small-cell lung cancer after a response to induction chemotherapy. EORTC 08941. Clin Lung Cancer. 2000 Aug;2(1):69-72; discussion 73. doi: 10.3816/clc.2000.n.020.