Chemotherapy or Observation in Treating Patients With Early Stage Non-Small Cell Lung Cancer

A Randomized Phase III Trial of Adjuvant Chemotherapy in Patients With Early Stage Non-Small Cell Lung Cancer Associated With Banking of Frozen Tumor Specimens and Collection of Gene Expression Profile Data

RATIONALE: Drugs used in chemotherapy, such as vinorelbine, cisplatin, docetaxel, gemcitabine, and pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether chemotherapy is more effective than observation in treating patients who have undergone surgery for stage I non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying four chemotherapy regimens to see how well they work compared with observation in treating patients with early stage non-small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: vinorelbine tartrate; Drug: cisplatin; Drug: docetaxel; Drug: pemetrexed disodium; Procedure: standard follow-up care

Detailed Description

OBJECTIVES:

Primary

• To determine the potential overall survival benefit of adjuvant chemotherapy in patients with early stage non-small cell lung cancer (NSCLC) randomized to chemotherapy compared to those randomized to the present standard of care (observation).
• To collect and process high-quality fresh frozen lung cancer tumor tissue for gene expression array generation from multiple institutions.

Secondary

• To evaluate selected genomic-based lung cancer prognostic models using data from the patients randomized to observation after resection.
• To characterize the rate of chemotherapy toxicity for the different chemotherapy treatment regimens.
• To assess quality of life (QOL) in early stage patients periodically after resection for NSCLC.
• To examine the impact of chemotherapy on QOL for patients receiving chemotherapy, as compared to patients in the observation arm.

OUTLINE: This is a multicenter study. Patients are stratified according to pathologic stage (I vs II) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms within 12 weeks after surgery.

All patients undergo complete resection of disease (i.e., lobectomy, sleeve lobectomy, bi-lobectomy, or pneumonectomy, but not segmentectomy or wedge resection).

• Arm I: Patients receive 1 of 3 chemotherapy regimens. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

  • Regimen 1: Patients receive vinorelbine ditartrate IV over 10 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1.
  • Regimen 2: Patients receive docetaxel IV over 60 minutes and cisplatin IV over 60 minutes on day 1.
  • Regimen 3: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1.
  • Regimen 4: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 60 minutes on day 1.
• Arm II: Patients receive standard care (observation). Tissue obtained at surgery is examined by RNA microarray analysis. A Lung Metagene Score (LMS) is determined for each patient and correlated with survival and response.

After completion of study treatment, patients are followed every 6 months for 5 years and then once a year for 7 years.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St. Vincent's Hospital - Melbourne
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Regional Medical Center
    • Birmingham, Alabama, United States, 35294
      • UAB Comprehensive Cancer Center
  • California
    • Burbank, California, United States, 91505
      • Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical Center
    • Glendale, California, United States, 91204
      • Glendale Memorial Hospital Comprehensive Cancer Center
    • La Jolla, California, United States, 92093-0658
      • Rebecca and John Moores UCSD Cancer Center
    • Pismo Beach, California, United States, 93449
    • Pomona, California, United States, 91767
      • Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102-5037
      • Helen and Harry Gray Cancer Center at Hartford Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute at Memorial Regional Hospital
    • Jupiter, Florida, United States, 33458
      • Ella Milbank Foshay Cancer Center at Jupiter Medical Center
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
  • Georgia
    • Savannah, Georgia, United States, 31405
      • Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60631
      • Resurrection Medical Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Elkhart, Indiana, United States, 46514-2098
      • Elkhart Clinic, LLC
    • Elkhart, Indiana, United States, 46514
      • Michiana Hematology-Oncology, PC - Elkhart
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • Mishawaka, Indiana, United States, 46545-1470
      • Michiana Hematology-Oncology, PC - South Bend
    • Mishawaka, Indiana, United States, 46545-1470
      • Saint Joseph Regional Medical Center
    • Plymouth, Indiana, United States, 46563
      • Michiana Hematology Oncology PC - Plymouth
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
    • Westville, Indiana, United States, 46391
      • Michiana Hematology Oncology PC - La Porte
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Associates
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Regional Cancer Center at Mercy Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
    • Lexington, Kentucky, United States, 40503-9985
      • Central Baptist Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center - Baton Rouge
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Center for Cancer Medicine and Blood Disorders - Scarborough
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center Cancer Center
    • Towson, Maryland, United States, 21204
      • Cancer Institute at St. Joseph Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Brigham and Women's Cancer Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
    • Newton, Massachusetts, United States, 02462
      • Newton-Wellesley Hospital
  • Michigan
    • Escanaba, Michigan, United States, 49431
      • Green Bay Oncology, Limited - Escanaba
    • Iron Mountain, Michigan, United States, 49801
      • Dickinson County Healthcare System
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Niles, Michigan, United States, 49120
      • Michiana Hematology Oncology PC - Niles
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital - Royal Oak Campus
    • Saint Joseph, Michigan, United States, 49085
      • Lakeside Cancer Specialists, PLLC
    • St. Joseph, Michigan, United States, 49085
      • Lakeland Regional Cancer Care Center - St. Joseph
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Cancer Resource Center - Lincoln
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68122
      • Immanuel Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegant Health Cancer Center at Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68131-2197
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68114
      • Methodist Estabrook Cancer Center
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
    • Hooksett, New Hampshire, United States, 03106
      • New Hampshire Oncology - Hematology, PA - Hooksett
  • New York
    • Poughkeepsie, New York, United States, 12601
      • Saint Francis Hospital Cancer Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
    • Utica, New York, United States, 13502
      • Faxton Regional Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
  • Ohio
    • Canton, Ohio, United States, 44708
      • Mercy Cancer Center at Mercy Medical Center
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105
      • Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Cancer Network at St. Luke's Hospital
    • Easton, Pennsylvania, United States, 18042
      • Easton Regional Cancer Center at Easton Hospital
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
    • New Castle, Pennsylvania, United States, 16105
      • Jameson Memorial Hospital - North Campus
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Centers
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Cancer Center at Allegheny General Hospital
  • Texas
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Lynchburg, Virginia, United States, 24501
      • Lynchburg Hematology-Oncology Clinic
  • Washington
    • Centralia, Washington, United States, 98531-9027
      • Providence Centralia Hospital
    • Federal Way, Washington, United States, 98003
      • St. Francis Hospital
    • Olympia, Washington, United States, 98506-5166
      • Providence St. Peter Hospital Regional Cancer Center
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Cancer Center
    • Tacoma, Washington, United States, 98405-3004
      • Franciscan Cancer Center at St. Joseph Medical Center
    • Tacoma, Washington, United States, 98405
      • Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • CCOP - Northwest
    • Tacoma, Washington, United States, 98405
      • MultiCare Regional Cancer Center at Tacoma General Hospital
    • Tacoma, Washington, United States, 98499
      • St. Clare Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54301-3526
      • Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
    • Green Bay, Wisconsin, United States, 54303
      • Green Bay Oncology, Limited at St. Mary's Hospital
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital Medical Center - Green Bay
    • Manitowoc, Wisconsin, United States, 54221-1450
      • Holy Family Memorial Medical Center Cancer Care Center
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Cancer Care Center at Bay Area Medical Center
    • Oconto Falls, Wisconsin, United States, 54154
      • Green Bay Oncology, Limited - Oconto Falls
    • Sheboygan, Wisconsin, United States, 53081
      • St. Nicholas Hospital
    • Sturgeon Bay, Wisconsin, United States, 54235
      • Green Bay Oncology, Limited - Sturgeon Bay

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 confirmed non-small cell lung cancer

  • Any variant allowed (e.g., pure or mixed bronchioloalveolar carcinoma or adenosquamous cell carcinoma)
  • Primary tumor must be T1a, T1b, T2a, or T2b by AJCC 7.0
  • No status

• Tumor measuring ≥ 2.0 cm but ≤ 7.0 cm in diameter by CT scan

  • The mass must have a source document to verify tumor size in the greatest dimension, which includes a CT scan report, a clinic note from the enrolling physician, and/or a printed image with caliper measurements on the lung mass

• Node-negative disease

  • Evidence of hilar or mediastinal node involvement by chest CT scan (> 1 cm diameter) must be assessed with mediastinoscopy, endo-esophageal ultrasound with biopsy, endo-bronchial ultrasound, bronchoscopy, or mediastinal nodal sampling before or at time of thoracotomy
• No locally advanced or metastatic disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Granulocytes ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Bilirubin ≤ 1.5 mg/dL
• AST < 1.5 times upper limit of normal (ULN)
• Serum creatinine ≤ 1.5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No history of prior or concurrent malignancy, except curatively treated carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin, surgically treated in situ carcinoma of the breast, or other cancer for which the patient has been disease-free for 3 years

PRIOR CONCURRENT THERAPY:

• More than 3 years since prior cytotoxic or anticancer treatment
• No concurrent treatment with hormones or other chemotherapeutic agents, except steroids given for adrenal failure, hormone administered for nondisease-related conditions (e.g., insulin for diabetes), or intermittent use of dexamethasone as an antiemetic
• No concurrent thoracic radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive cisplatin IV on day 1 and vinorelbine ditartrate IV on days 1 and 8 OR docetaxel IV and cytarabine IV on day 1 OR gemcitabine hydrochloride IV on days 1 and 8 and cytarabine IV on day 1 OR pemetrexed disodium IV and cisplatin IV on day 1.. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: gemcitabine hydrochloride; Given IV; Drug: vinorelbine tartrate; Given IV; Drug: cisplatin; Given IV; Drug: docetaxel; Given IV; Drug: pemetrexed disodium; Given IV
Experimental: Arm II; Patients receive standard care (observation).	Procedure: standard follow-up care; Standard care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) is defined as the time between formal registration and death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.	Up to 12 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David H. Harpole, MD, Duke Cancer Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: March 17, 2009
• First Submitted That Met QC Criteria: March 17, 2009
• First Posted (Estimate): March 18, 2009

Study Record Updates

• Last Update Posted (Actual): March 27, 2017
• Last Update Submitted That Met QC Criteria: February 7, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: squamous cell lung cancer; large cell lung cancer; adenocarcinoma of the lung; stage IA non-small cell lung cancer; stage IB non-small cell lung cancer; adenosquamous cell lung cancer; bronchoalveolar cell lung cancer; stage IIA 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; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Folic Acid Antagonists; Gemcitabine; Docetaxel; Cisplatin; Vinorelbine; Pemetrexed
• Other Study ID Numbers: CALGB-30506; CDR0000636895 (Registry Identifier: NCI Physician Data Query)