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Chemotherapy Plus Radiation Therapy With or Without Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00002550
Recruitment Status : Completed
First Posted : April 10, 2003
Last Update Posted : November 17, 2015
Information provided by (Responsible Party):

Study Description
Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known if chemotherapy plus radiation therapy is more effective with or without surgery for lung cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combining cisplatin, etoposide, and radiation therapy with or without surgery in treating patients who have stage IIIA non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Lung Cancer Drug: cisplatin Drug: etoposide Procedure: conventional surgery Radiation: radiation therapy Phase 3

Detailed Description:



  • Compare the progression-free survival, median (2-year) survival, and long-term (5-year) survival in patients with newly diagnosed, stage IIIA (N2) non-small cell lung cancer treated with radiotherapy concurrently with cisplatin and etoposide with or without surgical resection.


  • Compare the patterns of local and distant failure in patients treated with these regimens.
  • Determine the relationship of tobacco use, alcohol use, and diet with toxicity of these regimens and outcome in both men and women.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by contralateral mediastinal sampling or biopsy (yes vs no), tumor stage (T1 vs T2 vs T3), and performance status (70-80% vs 90-100%). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive induction with cisplatin IV over 1 hour on days 1 and 8 and etoposide IV over 1 hour on days 1-5. Treatment continues every 4 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning within 24 hours of the first dose of chemotherapy, patients undergo induction radiotherapy 5 days a week for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients without local progression or distant metastases at 2-4 weeks after completion of course 2 undergo resection approximately 3-5 weeks after completion of course 2. All visible, accessible bronchopulmonary, hilar, and mediastinal lymph nodes are excised. The choice of surgical procedure (thoracotomy, lobectomy, or pneumonectomy with en bloc resection of tumor extending into the parietal pleura, chest wall, pericardium, or diaphragm) is at the discretion of the surgeon. Patients who undergo resection receive 2 additional courses of chemotherapy alone beginning 4-6 weeks postoperatively. Patients with unresectable disease or who are medically unfit for or refuse resection receive 2 additional courses of chemotherapy alone beginning immediately after completion of course 2.
  • Arm II: Patients undergo induction chemoradiotherapy as in arm I but do not undergo resection. Patients without local progression or distant metastases within 1 week before anticipated completion of induction radiotherapy receive 2 additional courses of chemotherapy beginning immediately after completion of course 2. Patients without local or distant progression after completion of course 4 undergo boost radiotherapy for 8 days.

Patients are followed every 2 months for 1 year, every 3 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 510 patients will be accrued for this study within 4.9 years.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 429 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III Comparison Between Concurrent Chemotherapy Plus Radiotherapy and Concurrent Chemotherapy Plus Radiotherapy Followed by Surgical Resection for Stage IIIA (N2) Non-Small Cell Lung Cancer
Study Start Date : March 1994
Primary Completion Date : June 2004
Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: RT + chemotherapy followed by surgery + chemotherapy
Induction radiation therapy (RT) + concurrent induction chemotherapy followed by surgery and additional chemotherapy
Drug: cisplatin Drug: etoposide Procedure: conventional surgery Radiation: radiation therapy
Active Comparator: RT + chemotherapy followed by chemotherapy + RT
Induction RT + concurrent induction chemotherapy followed by additional chemotherapy + RT
Drug: cisplatin Drug: etoposide Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures :
  1. Median overall survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after patients have been potentially followed for 2.5 years. ]

Secondary Outcome Measures :
  1. Median Progression-free survival [ Time Frame: From randomization to date of death or last follow-up. Analysis occurs after patients have been potentially followed for 2.5 years. ]
  2. Patterns of local and distant failure [ Time Frame: From randomization to date of failure (local, regional or distant progression). Analysis occurs after patients have been potentially followed for 2.5 years. ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically proven newly diagnosed, stage IIIA (T1-3, N2) non-small cell lung cancer

    • Eligible subtypes:

      • Adenocarcinoma
      • Large cell carcinoma
      • Squamous cell carcinoma
      • Nonlobar and nondiffuse bronchoalveolar cell carcinoma
  • Measurable or evaluable disease on chest x-ray and/or contrast CT scan

    • Contrast thoracic CT required to complete staging
  • Single primary bronchogenic tumor (no more than 1 parenchymal lung lesion)
  • Pleural effusions allowed if 1 of the following conditions is met:

    • Negative cytology on thoracentesis if effusions present before mediastinoscopy or exploratory thoracotomy
    • Effusion seen on CT scan but not on chest x-ray and deemed too small to tap under CT or ultrasound guidance
  • Positive ipsilateral mediastinal node(s) with or without positive ipsilateral hilar nodes

    • Mediastinal nodes separate from primary lesion on CT scan or surgical exploration
    • Histologic or cytologic proof of N2 disease by thoracotomy, mediastinoscopy, mediastinotomy, Chamberlain procedure, Wang needle, or fine needle aspiration under bronchoscopic or CT guidance
    • Nodal biopsy or aspiration waived if all of the following conditions are met:

      • Paralyzed left true vocal cord documented by bronchoscopy or indirect laryngoscopy
      • Nodes visible in Level 5 region on CT scan
      • Distinct primary lesion separate from nodes on CT scan
    • All mediastinal nodal involvement mapped (positive or negative)
  • No positive nodes in contralateral mediastinum (supraclavicular areas and higher) and neck

    • Mediastinoscopy, mediastinotomy, Chamberlain procedure, or thoracotomy required for nodes larger than 1 cm on contrast CT scan
    • Surgery waived if nodes negative or no larger than 1 cm on CT scan
  • Lymphadenopathy allowed if biopsy proof of a benign cause
  • No metastases by contrast CT or MRI scan of the brain, bone scan, CT scan of the lungs to exclude other ipsilateral or contralateral parenchymal lesions, and contrast CT scan of the upper abdomen including entire liver and adrenals
  • No hepatomegaly or splenomegaly by physical examination or CT scan unless documentation of a benign cause
  • No pericardial effusion
  • No superior vena cava syndrome
  • No prior diagnosis of lung cancer



  • 18 and over

Performance status:

  • Karnofsky 90-100% (70-80% allowed if albumin at least 0.85 times lower limit of normal and weight loss no greater than 10% within 3 months before diagnosis)


  • White blood cell count (WBC) at least 4,000/mm^3 OR
  • Granulocyte count at least 2,000/mm^3
  • Platelet count normal
  • Hemoglobin at least 10.0 g/dL (less than 8.5 g/dL allowed if no marrow involvement with tumor)


  • See Performance status
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)*
  • Serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) no greater than 1.5 times ULN* NOTE: * Unless documentation of a benign cause


  • Creatinine clearance at least 50 mL/min


  • No myocardial infarction within the past 3 months
  • No active angina
  • No unstable arrhythmia
  • No congestive heart failure


  • Forced expiratory volume at one second (FEV1) at least 2.0 liters OR
  • Predicted postresection FEV1 at least 800 mL based on quantitative V/Q scan
  • Diffusion capacity of lung for carbon monoxide (DLCO) at least 50% predicted (corrected for hemoglobin) if pneumonectomy planned or likely after induction chemotherapy


  • No clinically significant hearing loss unless willing to accept the potential of further loss
  • No symptomatic peripheral neuropathy
  • No peptic ulcer disease under active treatment
  • No other medical illness not controllable by appropriate medical therapy
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception


Biologic therapy:

  • No concurrent colony-stimulating factors


  • No prior chemotherapy for lung cancer
  • No concurrent chemotherapy for another condition (such as arthritis)

Endocrine therapy:

  • Not specified


  • No prior radiotherapy for lung cancer


  • See Disease Characteristics
  • No prior resection of primary tumor
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002550

United States, Illinois
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
Veterans Affairs Medical Center - Indianapolis (Roudebush)
Indianapolis, Indiana, United States, 46202
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
United States, Michigan
CCOP - Ann Arbor Regional
Ann Arbor, Michigan, United States, 48106
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, New York
University of Rochester Cancer Center
Rochester, New York, United States, 14642
United States, Ohio
Ireland Cancer Center
Cleveland, Ohio, United States, 44106-5065
CCOP - Toledo Community Hospital Oncology Program
Toledo, Ohio, United States, 43623-3456
United States, Pennsylvania
Hahnemann University Hospital
Philadelphia, Pennsylvania, United States, 19102-1192
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15213-3489
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
United States, Wisconsin
CCOP - Green Bay
Green Bay, Wisconsin, United States, 54301
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Veterans Affairs Medical Center - Milwaukee (Zablocki)
Milwaukee, Wisconsin, United States, 53295
South Africa
Pretoria Academic Hospitals
Pretoria, South Africa, 0001
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Southwest Oncology Group
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
North Central Cancer Treatment Group
NCIC Clinical Trials Group
Study Chair: David S. Ettinger, MD Sidney Kimmel Comprehensive Cancer Center
Principal Investigator: Kathy S. Albain, MD Loyola University
Study Chair: David H. Johnson, MD Vanderbilt-Ingram Cancer Center
Study Chair: Bruce E. Johnson, MD Dana-Farber Cancer Institute
Study Chair: Mark R. Green, MD Medical University of South Carolina
Study Chair: Robert C. Miller, MD Mayo Clinic
Study Chair: Yvon Cormier, MD L'Hopital Laval
More Information

Albain KS, Swann RS, Rusch VR, et al.: Phase III study of concurrent chemotherapy and radiotherapy (CT/RT) vs CT/RT followed by surgical resection for stage IIIA(pN2) non-small cell lung cancer (NSCLC): outcomes update of North American Intergroup 0139 (RTOG 9309). [Abstract] J Clin Oncol 23 (Suppl 16): A-7014, 624s, 2005.
Albain KS, Scott CB, Rusch VR, et al.: Phase III comparison of concurrent chemotherapy plus radiotherapy (CT/RT) and CT/RT followed by surgical resection for stage IIIA(pN2) non-small cell lung cancer (NSCLC): initial results from intergroup trial 0139 (RTOG 93-09) . [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2497, 2003.
Turrisi AT, Scott CB, Rusch VR, et al.: Randomized trial of chemoradiotherapy to 61 Gy [no S] versus chemoradiotherapy to 45 Gy followed by surgery [S] using cisplatin etoposide in stage IIIa non-small cell lung cancer (NSCLC): intergroup trial 0139, RTOG (9309). [Abstract] Int J Radiat Oncol Biol Phys 57 (2 Suppl): S125-6, 2003.
Machtay M, Swann S, Komaki R, et al.: What is the meaning of local-regional control after chemoradiation for locally advanced NSCLC? An RTOG analysis. [Abstract] Lung Cancer 50 (Suppl 2): A-O-041, S17, 2005.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00002550     History of Changes
Other Study ID Numbers: RTOG-9309
First Posted: April 10, 2003    Key Record Dates
Last Update Posted: November 17, 2015
Last Verified: November 2015

Keywords provided by Radiation Therapy Oncology Group:
squamous cell lung cancer
large cell lung cancer
stage IIIA non-small cell lung cancer
adenocarcinoma of the lung
bronchoalveolar cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action