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

NCT ID: NCT00002623

Last Updated: 2012-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 640 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1994-12-31

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.

Conditions

Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

carboplatin

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ted A.W. Splinter, MD

Role: STUDY_CHAIR

University Medical Center Rotterdam at Erasmus Medical Center

Locations

Algemeen Ziekenhuis Middelheim

Antwerp, , Belgium

A.Z. St. Jan

Bruges, , 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, , Belgium

Academisch Ziekenhuis Utrecht

Vandœuvre-lès-Nancy, , France

Istituto Nazionale per la Ricerca sul Cancro

Genoa (Genova), , Italy

Groot Ziekengasthuis 's-Hertogenbosch

's-Hertogenbosch, , Netherlands

Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

Antoni van Leeuwenhoekhuis

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

University Hospital - Rotterdam Dijkzigt

Rotterdam, , Netherlands

Erasmus Medical Center

Rotterdam, , Netherlands

Twee Steden Ziekenhuis Vestiging Tilburg

Tilburg, , Netherlands

Diakonessenhuis Utrecht

Utrecht, , Netherlands

Sophia Ziekehuis

Zwolle, , Netherlands

Leicester Royal Infirmary

Leicester, England, United Kingdom

Royal Marsden Hospital

Sutton, England, United Kingdom

Royal Victoria Hospital

Belfast, Northern Ireland, United Kingdom

Countries

Belgium; France; Italy; Netherlands; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 18279061 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17374834 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16785054 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 16055865 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 14731343 (View on PubMed)

Other Identifiers

EORTC-08941

Identifier Type: -

Identifier Source: secondary_id

EORTC-08941

Identifier Type: -

Identifier Source: org_study_id