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

Primary Purpose

Lung Cancer

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
cisplatin
etoposide
conventional surgery
radiation therapy
Sponsored by
Radiation Therapy Oncology Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring squamous cell lung cancer, large cell lung cancer, stage IIIA non-small cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: 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 PATIENT CHARACTERISTICS: Age: 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) Hematopoietic: 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) Hepatic: 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 Renal: Creatinine clearance at least 50 mL/min Cardiovascular: No myocardial infarction within the past 3 months No active angina No unstable arrhythmia No congestive heart failure Pulmonary: 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 Other: 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 PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent colony-stimulating factors Chemotherapy: No prior chemotherapy for lung cancer No concurrent chemotherapy for another condition (such as arthritis) Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy for lung cancer Surgery: See Disease Characteristics No prior resection of primary tumor

Sites / Locations

  • CCOP - Carle Cancer Center
  • Indiana University Cancer Center
  • Veterans Affairs Medical Center - Indianapolis (Roudebush)
  • CCOP - Cedar Rapids Oncology Project
  • CCOP - Ann Arbor Regional
  • CCOP - Missouri Valley Cancer Consortium
  • University of Rochester Cancer Center
  • Ireland Cancer Center
  • CCOP - Toledo Community Hospital Oncology Program
  • Hahnemann University Hospital
  • University of Pittsburgh Cancer Institute
  • Vanderbilt-Ingram Cancer Center
  • CCOP - Green Bay
  • Medical College of Wisconsin
  • Veterans Affairs Medical Center - Milwaukee (Zablocki)
  • Pretoria Academic Hospitals

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

RT + chemotherapy followed by surgery + chemotherapy

RT + chemotherapy followed by chemotherapy + RT

Arm Description

Induction radiation therapy (RT) + concurrent induction chemotherapy followed by surgery and additional chemotherapy

Induction RT + concurrent induction chemotherapy followed by additional chemotherapy + RT

Outcomes

Primary Outcome Measures

Median overall survival

Secondary Outcome Measures

Median Progression-free survival
Patterns of local and distant failure

Full Information

First Posted
November 1, 1999
Last Updated
November 14, 2015
Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI), SWOG Cancer Research Network, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, North Central Cancer Treatment Group, NCIC Clinical Trials Group
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1. Study Identification

Unique Protocol Identification Number
NCT00002550
Brief Title
Chemotherapy Plus Radiation Therapy With or Without Surgery in Treating Patients With Stage IIIA Non-small Cell Lung Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
November 2015
Overall Recruitment Status
Completed
Study Start Date
March 1994 (undefined)
Primary Completion Date
June 2004 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI), SWOG Cancer Research Network, Eastern Cooperative Oncology Group, Cancer and Leukemia Group B, North Central Cancer Treatment Group, NCIC Clinical Trials Group

4. Oversight

Data Monitoring Committee
Yes

5. 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.
Detailed Description
OBJECTIVES: Primary 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. Secondary 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
squamous cell lung cancer, large cell lung cancer, stage IIIA non-small cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
429 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RT + chemotherapy followed by surgery + chemotherapy
Arm Type
Experimental
Arm Description
Induction radiation therapy (RT) + concurrent induction chemotherapy followed by surgery and additional chemotherapy
Arm Title
RT + chemotherapy followed by chemotherapy + RT
Arm Type
Active Comparator
Arm Description
Induction RT + concurrent induction chemotherapy followed by additional chemotherapy + RT
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Procedure
Intervention Name(s)
conventional surgery
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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.
Title
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: 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 PATIENT CHARACTERISTICS: Age: 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) Hematopoietic: 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) Hepatic: 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 Renal: Creatinine clearance at least 50 mL/min Cardiovascular: No myocardial infarction within the past 3 months No active angina No unstable arrhythmia No congestive heart failure Pulmonary: 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 Other: 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 PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent colony-stimulating factors Chemotherapy: No prior chemotherapy for lung cancer No concurrent chemotherapy for another condition (such as arthritis) Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy for lung cancer Surgery: See Disease Characteristics No prior resection of primary tumor
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David S. Ettinger, MD
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Kathy S. Albain, MD
Organizational Affiliation
Loyola University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David H. Johnson, MD
Organizational Affiliation
Vanderbilt-Ingram Cancer Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Bruce E. Johnson, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mark R. Green, MD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Robert C. Miller, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Yvon Cormier, MD
Organizational Affiliation
L'Hopital Laval
Official's Role
Study Chair
Facility Information:
Facility Name
CCOP - Carle Cancer Center
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
Indiana University Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202-5289
Country
United States
Facility Name
Veterans Affairs Medical Center - Indianapolis (Roudebush)
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
CCOP - Cedar Rapids Oncology Project
City
Cedar Rapids
State/Province
Iowa
ZIP/Postal Code
52403-1206
Country
United States
Facility Name
CCOP - Ann Arbor Regional
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106
Country
United States
Facility Name
CCOP - Missouri Valley Cancer Consortium
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68106
Country
United States
Facility Name
University of Rochester Cancer Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Ireland Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States
Facility Name
CCOP - Toledo Community Hospital Oncology Program
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43623-3456
Country
United States
Facility Name
Hahnemann University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19102-1192
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213-3489
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6838
Country
United States
Facility Name
CCOP - Green Bay
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54301
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Veterans Affairs Medical Center - Milwaukee (Zablocki)
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53295
Country
United States
Facility Name
Pretoria Academic Hospitals
City
Pretoria
ZIP/Postal Code
0001
Country
South Africa

12. IPD Sharing Statement

Citations:
PubMed Identifier
20980108
Citation
Machtay M, Bae K, Movsas B, Paulus R, Gore EM, Komaki R, Albain K, Sause WT, Curran WJ. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non-small cell lung carcinoma treated with chemoradiation: an analysis of the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):425-34. doi: 10.1016/j.ijrobp.2010.09.004. Epub 2010 Oct 25.
Results Reference
background
Citation
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.
Results Reference
background
PubMed Identifier
19632716
Citation
Albain KS, Swann RS, Rusch VW, Turrisi AT 3rd, Shepherd FA, Smith C, Chen Y, Livingston RB, Feins RH, Gandara DR, Fry WA, Darling G, Johnson DH, Green MR, Miller RC, Ley J, Sause WT, Cox JD. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009 Aug 1;374(9687):379-86. doi: 10.1016/S0140-6736(09)60737-6. Epub 2009 Jul 24.
Results Reference
result
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result

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

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