Chemotherapy Followed by Surgery or Radiation Therapy in Treating Patients With Stage III Non-small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

RANDOMIZED TRIAL OF SURGERY VERSUS RADIOTHERAPY IN PATIENTS WITH STAGE IIIa NON-SMALL CELL LUNG CANCER AFTER A RESPONSE TO INDUCTION-CHEMOTHERAPY

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002623
• Other study ID #: EORTC-08941
• Secondary ID: EORTC-08941
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: June 29, 2012
• Start date: December 1994

Study information

• Verified date: June 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 640
• Est. primary completion date: December 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• carboplatin

• cisplatin

Procedure:
• conventional surgery

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis Middelheim	Antwerp
Belgium	A.Z. St. Jan	Brugge
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Hopital de Jolimont	Haine Saint Paul
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	CHR - Clinique Saint Joseph - Hopital de Warqueguies	Mons
Belgium	Clinique Universitaire De Mont-Godinne	Mont-Godinne Yvoir
Belgium	Stedelijk Ziekenhuis	Roesclare
France	Academisch Ziekenhuis Utrecht	Vandoeuvre-les-Nancy
Italy	Istituto Nazionale per la Ricerca sul Cancro	Genoa (Genova)
Netherlands	Groot Ziekengasthuis 's-Hertogenbosch	's-Hertogenbosch
Netherlands	Antoni van Leeuwenhoekhuis	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Arnhems Radiotherapeutisch Instituut	Arnhem
Netherlands	Ziekenhuis St Jansdal	Harderwijk
Netherlands	Atrium Medical Centre	Heerlen
Netherlands	Elkerliek Ziekenhuis	Helmond
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Sint Antonius Ziekenhuis	Nieuwegein
Netherlands	Canisius-Wilhelmina Ziekenhuis	Nijmegen
Netherlands	University Medical Center Nijmegen	Nijmegen
Netherlands	Saint Franciscus Ziekenhuis	Roosendaal
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	University Hospital - Rotterdam Dijkzigt	Rotterdam
Netherlands	Twee Steden Ziekenhuis Vestiging Tilburg	Tilburg
Netherlands	Diakonessenhuis Utrecht	Utrecht
Netherlands	Sophia Ziekehuis	Zwolle
United Kingdom	Royal Victoria Hospital	Belfast	Northern Ireland
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Marsden Hospital	Sutton	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  France,  Italy,  Netherlands,  United Kingdom, 

References & Publications (9)

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 tr — View Citation

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 A

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. Review. — View 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 08

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 analy

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 — View 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.

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. — View 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.