Chemotherapy Followed by Surgery or Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer - Full Text View

Sponsor:	European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002623

Purpose

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.

Condition	Intervention	Phase
Lung Cancer	Drug: carboplatin Drug: cisplatin Procedure: conventional surgery Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	RANDOMIZED TRIAL OF SURGERY VERSUS RADIOTHERAPY IN PATIENTS WITH STAGE IIIa NON-SMALL CELL LUNG CANCER AFTER A RESPONSE TO INDUCTION-CHEMOTHERAPY

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Surgery

Drug Information available for: Cisplatin Carboplatin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	640
Study Start Date:	December 1994

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002623

Locations

Belgium
A.Z. St. Jan
Brugge, Belgium, 8000
Algemeen Ziekenhuis Middelheim
Antwerp, Belgium, 2020
CHR - Clinique Saint Joseph - Hopital de Warqueguies
Mons, Belgium, B-7000
U.Z. Gasthuisberg
Leuven, Belgium, B-3000
Hopital de Jolimont
Haine Saint Paul, Belgium, 7100
Stedelijk Ziekenhuis
Roesclare, Belgium, 8800
Clinique Universitaire De Mont-Godinne
Mont-Godinne Yvoir, Belgium, 5530
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
France
Academisch Ziekenhuis Utrecht
Vandoeuvre-les-Nancy, France, 54511
Italy
Istituto Nazionale per la Ricerca sul Cancro
Genoa (Genova), Italy, 16132
Netherlands
Antoni van Leeuwenhoekhuis
Amsterdam, Netherlands, 1066 CX
Diakonessenhuis Utrecht
Utrecht, Netherlands, 3508 TG
Atrium Medical Centre
Heerlen, Netherlands, 6419 PC
Canisius-Wilhelmina Ziekenhuis
Nijmegen, Netherlands, 6532 SZ
Arnhems Radiotherapeutisch Instituut
Arnhem, Netherlands, 6815 AD
Elkerliek Ziekenhuis
Helmond, Netherlands, 5707-HA
Erasmus Medical Center
Rotterdam, Netherlands, 3075 EA
Groot Ziekengasthuis 's-Hertogenbosch
's-Hertogenbosch, Netherlands, 5211 NL
Leiden University Medical Center
Leiden, Netherlands, 2300 CA
Twee Steden Ziekenhuis Vestiging Tilburg
Tilburg, Netherlands, 5042 AD
Sint Antonius Ziekenhuis
Nieuwegein, Netherlands, 3435 CM
Sophia Ziekehuis
Zwolle, Netherlands, 8000 GK
Saint Franciscus Ziekenhuis
Roosendaal, Netherlands, 4708 AE
University Hospital - Rotterdam Dijkzigt
Rotterdam, Netherlands, 3000 CA
University Medical Center Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Vrije Universiteit Medisch Centrum
Amsterdam, Netherlands, 1001HV
Ziekenhuis St Jansdal
Harderwijk, Netherlands, 3840 AC
United Kingdom, England
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Royal Marsden Hospital
Sutton, England, United Kingdom, SM2 5PT
United Kingdom, Northern Ireland
Royal Victoria Hospital
Belfast, Northern Ireland, United Kingdom, BT12 6BA

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Investigators

Study Chair:

Ted A.W. Splinter, MD

University Medical Center Rotterdam at Erasmus Medical Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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; on behalf of 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.

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.

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.

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.

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.

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.

Splinter TA, Kirkpatrick A, Van Meerbeeck J, et al.: Randomized trial of surgery versus radiotherapy in patients with stage IIIA non-small cell lung cancer after a response to induction chemotherapy. Intergroup study 08941. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A1742, 453a, 1998.

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.

Study ID Numbers:	CDR0000063983, EORTC-08941
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00002623 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Antineoplastic Agents
Physiological Effects of Drugs
Carboplatin
Pharmacologic Actions
Carcinoma
Neoplasms

Neoplasms by Site
Radiation-Sensitizing Agents
Respiratory Tract Diseases
Cisplatin
Lung Neoplasms
Therapeutic Uses
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 27, 2009