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

NCT00002550 | Completed Phase 3 DMC

• 9 other identifiers: RTOG-9309CDR0000063333CAN-NCIC-BR13CLB-9592E-R9309NCCTG-R9309NCI-94-C-0043SWOG-9336INT-0139
• Study Type: interventional
• Target: 429
• Locations: 2 countries
• Sites: 16

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Median overall survival

  From randomization to date of death or last follow-up. Analysis occurs after patients have been potentially followed for 2.5 years.

Secondary Outcomes (2)

• Median Progression-free survival

  From randomization to date of death or last follow-up. Analysis occurs after patients have been potentially followed for 2.5 years.

• Patterns of local and distant failure

  From randomization to date of failure (local, regional or distant progression). Analysis occurs after patients have been potentially followed for 2.5 years.

Study Arms (2)

RT + chemotherapy followed by surgery + chemotherapy

EXPERIMENTAL

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

Drug: cisplatin; Drug: etoposide; Procedure: conventional surgery; Radiation: radiation therapy

RT + chemotherapy followed by chemotherapy + RT

ACTIVE COMPARATOR

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

Drug: cisplatin; Drug: etoposide; Radiation: radiation therapy

Interventions

cisplatin DRUG

RT + chemotherapy followed by chemotherapy + RT; RT + chemotherapy followed by surgery + chemotherapy

etoposide DRUG

RT + chemotherapy followed by chemotherapy + RT; RT + chemotherapy followed by surgery + chemotherapy

conventional surgery PROCEDURE

RT + chemotherapy followed by surgery + chemotherapy

radiation therapy RADIATION

RT + chemotherapy followed by chemotherapy + RT; RT + chemotherapy followed by surgery + chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• SWOG Cancer Research Network: collaborator
• Eastern Cooperative Oncology Group: collaborator
• Cancer and Leukemia Group B: collaborator
• North Central Cancer Treatment Group: collaborator
• NCIC Clinical Trials Group: collaborator

Study Sites (16)

CCOP - Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Veterans Affairs Medical Center - Indianapolis (Roudebush)

Indianapolis, Indiana, 46202, United States

Location

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, 52403-1206, United States

Location

CCOP - Ann Arbor Regional

Ann Arbor, Michigan, 48106, United States

Location

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

University of Rochester Cancer Center

Rochester, New York, 14642, United States

Location

Ireland Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

CCOP - Toledo Community Hospital Oncology Program

Toledo, Ohio, 43623-3456, United States

Location

Hahnemann University Hospital

Philadelphia, Pennsylvania, 19102-1192, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15213-3489, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

CCOP - Green Bay

Green Bay, Wisconsin, 54301, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Veterans Affairs Medical Center - Milwaukee (Zablocki)

Milwaukee, Wisconsin, 53295, United States

Location

Pretoria Academic Hospitals

Pretoria, 0001, South Africa

Location

Related Publications (6)

• 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.

  PMID: 20980108 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 19632716 RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Adenocarcinoma, Bronchiolo-Alveolar

Interventions

Cisplatin; Etoposide; Radiotherapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Therapeutics

Study Officials

• David S. Ettinger, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  STUDY CHAIR

• Kathy S. Albain, MD

  Loyola University

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: April 10, 2003
• Study Start: March 1, 1994
• Primary Completion: June 1, 2004
• Study Completion: November 1, 2013
• Last Updated: November 17, 2015

Record last verified: 2015-11

Locations

ZA (1); US (15)