Chemotherapy Plus Radiation Therapy in Treating Patients With Stage I, Stage II, or Stage III Non-small Cell Lung Cancer That Cannot Be Surgically Removed

A Randomized Phase III Study Comparing Induction Chemotherapy to Daily Low Dose Cisplatin Both Combined With High Dose Radiotherapy Using Concomitant Boost Technique in Patients With Inoperable Non-Small Cell Lung Cancer Stage I, II, and Low Volume Stage III

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy used high-energy x-rays to damage tumor cells. It is not yet know whether chemotherapy followed by radiation therapy is more effective than chemotherapy given with radiation therapy for non-small cell lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of chemotherapy and radiation therapy in treating patients who have unresectable stage I, stage II, or stage III non-small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer
• Intervention / Treatment: Radiation: radiation therapy; Drug: cisplatin; Drug: gemcitabine hydrochloride

Detailed Description

OBJECTIVES:

• Compare survival, disease-free survival, local control, and pattern of recurrence in patients with unresectable stage I, II, or low-volume stage III non-small lung cancer treated with high-dose radiotherapy either preceded by induction chemotherapy with gemcitabine and cisplatin or combined with daily cisplatin.
• Compare the acute and late toxic effects of these regimens in these patients.
• Determine the quality of life of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (0 vs 1), TNM stage, and participating center. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 3-6 hours on day 2. Treatment is repeated once 21 days later. Patients undergo high-dose accelerated conformal radiotherapy beginning on week 9 (day 57), 5 days a week, for 24 fractions, using a concurrent boost technique up to 66 Gy.
• Arm II: Patients receive low-dose cisplatin IV followed 1-2 hours later by high-dose accelerated conformal radiotherapy. Treatment continues daily, 5 days a week, for 24 fractions, using a concurrent boost technique up to 66 Gy.

Quality of life is assessed before treatment and at weeks 9-11, 19, 27, and 35.

Patients are followed at 3 weeks, 6-7 weeks, and then every 8 weeks thereafter.

PROJECTED ACCRUAL: A total of 418 patients (209 per arm) will be accrued for this study within 5 years.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2020
    • Algemeen Ziekenhuis Middelheim
  • Haine Saint Paul, Belgium, 7100
    • Hopital de Jolimont
• France
  • Grenoble, France, 38043
    • Chr De Grenoble - La Tronche
• Germany
  • Trier, Germany, D-54219
    • Mutterhaus der Borromäerinnen
• Netherlands
  • 's-Gravenhage (Den Haag, The Hague), Netherlands, 2501 CK
    • Medisch Centrum Haaglanden
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
  • Amsterdam, Netherlands, 1066 CX
    • Antoni van Leeuwenhoekhuis
  • Apeldoorn, Netherlands, 7334 DZ
    • Gelre Ziekenhuizen - Lokatie Lukas
  • Breda, Netherlands, 4818 CK
    • Amphia Ziekenhuis - locatie Molengracht
  • Breda, Netherlands, 4810 EV
    • Amphia Ziekenhuis
  • Delft, Netherlands, NL 2600 GA
    • Reinier de Graaf Group
  • Deventer, Netherlands, 7400 AC
    • Radiotherapeutisch Instituut-(Riso)
  • Eindhoven, Netherlands, 5602 ZA
    • Catharina Ziekenhuis
  • Tilburg, Netherlands, 5042 AD
    • Twee Steden Ziekenhuis Vestiging Tilburg
  • Tilburg, Netherlands, 5042 SB
    • Dr. Bernard Verbeeten Instituut
  • Zwolle, Netherlands, 8000 GK
    • Sophia Ziekehuis
• United Kingdom
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Western General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer

  • Stage I, II, III (T1-4, N0-3, M0)

    • No metastases to supraclavicular, contralateral hilar, or contralateral scalene lymph nodes
  • Medically inoperable or unresectable
• No pleural or pericardial effusion (except with repeated negative cytology)

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• ECOG 0 or 1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 6.8 g/dL
• No hemoptysis causing a decrease of hemoglobin of 1 g/dL or more within 24 hours

Hepatic:

• Not specified

Renal:

• Creatinine no greater than 1.25 times normal OR
• Creatinine clearance greater than 70 mL/min

Cardiovascular:

• No evidence of heart failure
• No myocardial infarction within the past 6 months
• No superior vena cava syndrome

Pulmonary:

• FEV1 at least 1 L
• No pre-existing fibrotic lung disease
• No postobstructive pneumonia preventing exact delineation of tumor volume
• Diffusion capacity at least 60%

Other:

• No weight loss of more than 10% in the past 3 months
• No uncontrolled infection
• No serious medical risk factors involving any of the major organ systems that would preclude adherence to the study treatment schedule

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent immunotherapy

Chemotherapy:

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the chest
• Maximum length of the esophagus receiving 40 Gy no greater than 18 cm
• Maximum length of the esophagus receiving 66 Gy no greater than 12 cm
• Must limit the spinal cord dose to a maximum of 50 Gy
• Must be able to exclude 25% of the heart from the boost volume

Surgery:

• Not specified

Other:

• No other concurrent experimental medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Study Chair: Jose Belderbos, MD, The Netherlands Cancer Institute

Publications and helpful links

General Publications

• Belderbos J, Uitterhoeve L, van Zandwijk N, Belderbos H, Rodrigus P, van de Vaart P, Price A, van Walree N, Legrand C, Dussenne S, Bartelink H, Giaccone G, Koning C; EORTC LCG and RT Group. Randomised trial of sequential versus concurrent chemo-radiotherapy in patients with inoperable non-small cell lung cancer (EORTC 08972-22973). Eur J Cancer. 2007 Jan;43(1):114-21. doi: 10.1016/j.ejca.2006.09.005. Epub 2006 Nov 3.

Study record dates

Study Major Dates

• Study Start: February 1, 1999
• Primary Completion (Actual): March 1, 2003

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 18, 2012
• Last Update Submitted That Met QC Criteria: July 17, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: stage I non-small cell lung cancer; stage II non-small cell lung cancer; stage III non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: EORTC-08972-22973; EORTC-08972