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High-Dose or Standard-Dose Radiation Therapy and Chemotherapy in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), May 2009
First Received: September 20, 2007   Last Updated: May 5, 2009   History of Changes
Sponsors and Collaborators: Radiation Therapy Oncology Group
National Cancer Institute (NCI)
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00533949
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

Drugs used in chemotherapy, such as paclitaxel, carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether high-dose radiation therapy is more effective than standard-dose radiation therapy when given together with combination chemotherapy in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying high-dose radiation therapy given together with cetuximab and chemotherapy to see how well it works compared with standard-dose radiation therapy and chemotherapy in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery.


Condition Intervention Phase
Cancer-Related Problem/Condition
Lung Cancer
Biological: cetuximab
Drug: carboplatin
Drug: paclitaxel
Radiation: 3-dimensional conformal radiation therapy
Phase III

MedlinePlus related topics: Cancer Lung Cancer Radiation Therapy Surgery
Drug Information available for: Paclitaxel Carboplatin Cetuximab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: A Randomized Phase III Comparison of Standard-Dose (60 Gy) Versus High-Dose (74 Gy) Conformal Radiotherapy With Concurrent and Consolidation Carboplatin/Paclitaxel in Patients With Stage IIIA/IIIB Non-Small Cell Lung Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall (Failure: death from any cause) survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (Failure: occurrence of local or regional progression, distant metastases, or death from any cause) [ Designated as safety issue: No ]
  • Local-regional failure (Failure: occurrence of local or regional progression) [ Designated as safety issue: No ]
  • Grade 3-5 esophagitis and pneumonitis adverse events as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Other grade 3-5 adverse events as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Death during or within 30 days of discontinuation of protocol treatment [ Designated as safety issue: Yes ]
  • Quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) and lung cancer subscale (LCS) [ Designated as safety issue: No ]
  • Patient-reported swallowing ability [ Designated as safety issue: No ]
  • Quality-adjusted survival based on EuroQoL (EQ5D)-derived health utility score [ Designated as safety issue: No ]
  • Correlation of tumor markers with overall survival, local-regional failure, and QOL [ Designated as safety issue: No ]
  • Prognostic and predictive effects of gross tumor volume on overall survival [ Designated as safety issue: No ]
  • Prognostic value of pre-treatment standardized uptake value (SUV) of PET scan in predicting survival, distant metastasis, and local-regional control [ Designated as safety issue: No ]

Estimated Enrollment: 500
Study Start Date: November 2007
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Active Comparator

Patients undergo standard-dose radiotherapy 5 days a week for 6 weeks. Patients receive concurrent chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 35 and 42. Patients also receive consolidation treatment of paclitaxel and carboplatin.

Treatment repeats in the absence of disease progression or unacceptable toxicity.

Drug: carboplatin
Given IV over 30 minutes
Drug: paclitaxel
Given IV over 1 hour
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiation therapy 5 days a week
Arm II: Experimental
Patients undergo high-dose radiotherapy 5 days per week for 7.5 weeks. Patient also receive concurrent paclitaxel and carboplatin and receive consolidation treatment as in Arm I.
Drug: carboplatin
Given IV over 30 minutes
Drug: paclitaxel
Given IV over 1 hour
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiation therapy 5 days a week
Arm III: Experimental
Patients undergo standard-dose radiotherapy as in Arm I. Patients receive cetuximab and receive concurrent chemotherapy and consolidation treatment comprising cetuximab, paclitaxel, and carboplatin periodically for up to 16 weeks.
Biological: cetuximab
Given IV
Arm IV: Experimental
Patients undergo high-dose radiotherapy as in arb II and receive concurrent cetuximab, concurrent chemotherapy, and consolidation treatment as in Arm III.
Biological: cetuximab
Given IV

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed newly diagnosed non-small cell lung cancer (NSCLC)

    • Stage IIIA or IIIB disease

      • N3 supraclavicular disease or contralateral hilar lymph node involvement (i.e. greater than 1.5 cm on short axis or positive on PET scan) not allowed
    • Unresectable or inoperable disease
  • No distant metastases
  • No Pancoast tumors
  • No planned treatment with a maximum dose of ≥ 66 Gy to the ipsilateral brachial plexus
  • Pleural effusion allowed provided effusion is minimal and none of the following conditions are present:

    • Cytologically positive pleural effusion detectable by CT scan and chest x-ray (pleuracentesis required to confirm negative cytology of pleural fluid)
    • Greater than minimal pleural effusions (minimal effusions not detectable by chest x-ray and too small to tap safely are allowed)
    • Exudative pleural effusions, regardless of cytology
    • Malignant pleural effusion (T4 incurable disease)
  • Measurable or evaluable disease

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • ANC ≥ 1,800 cells/mm³
  • Platelet count ≥ 100,000 cells/mm³
  • Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed)
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Bilirubin normal
  • AST and ALT < 2.5 times upper limit of normal
  • PFTs including FEV1 ≥ 1.2 L/sec or ≥ 50% predicted (best value obtained prior to or after use of bronchodilator)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective protection
  • No uncontrolled neuropathy ≥ grade 2
  • Patients with post-obstructive pneumonia allowed
  • No prior invasive malignancy, except nonmelanoma skin cancer, carcinoma in situ of the breast, oral cavity, or cervix, unless the patient has been disease-free for the past 3 years
  • No prior severe infusion reaction to a monoclonal antibody
  • No weight loss of ≥ 10% within the past 4 weeks
  • No history of allergic reaction to paclitaxel or other taxanes, or to carboplatin
  • No severe, active comorbidity, including any of the following:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring IV antibiotics at the time of study entry
    • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or within past 30 days precluding study therapy
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • AIDS
  • No significant history of uncontrolled cardiac disease, including any of the following:

    • Uncontrolled hypertension
    • unstable angina
    • Myocardial infarction within the past 6 months
    • Uncontrolled congestive heart failure
    • Cardiomyopathy with decreased ejection fraction

PRIOR CONCURRENT THERAPY:

  • At least 3 weeks since prior exploratory thoracotomy (if performed)
  • Prior systemic chemotherapy allowed, provided it was not given for NSCLC
  • No prior therapy that specifically and directly targets the EGFR pathway
  • No prior radiotherapy to the region of NSCLC that would result in overlap of radiotherapy fields
  • No concurrent WBC growth factors (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF]) given during radiotherapy or prophylactically during consolidation chemotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00533949

  Show 100 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Investigators
Principal Investigator: Jeffrey Bradley, MD Mallinckrodt Institute of Radiology at Washington University Medical Center
Investigator: Hak Choy, MD Simmons Cancer Center
Investigator: Gregory A. Masters, MD CCOP - Christiana Care Health Services
Study Chair: Steven E. Schild, MD Mayo Clinic Scottsdale
Investigator: Alex A. Adjei, MD, PhD Roswell Park Cancer Institute
Study Chair: Jeffrey A. Bogart, MD State University of New York - Upstate Medical University
Investigator: Arthur William Blackstock, MD Wake Forest University
Investigator: Mark A. Socinski, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Radiation Therapy Oncology Group ( Walter John Curran, Jr )
Study ID Numbers: CDR0000564240, RTOG-0617, NCCTG-N0628, CALGB-30609
Study First Received: September 20, 2007
Last Updated: May 5, 2009
ClinicalTrials.gov Identifier: NCT00533949     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
radiation toxicity
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer

Study placed in the following topic categories:
Thoracic Neoplasms
Cetuximab
Carboplatin
Antimitotic Agents
Carcinoma
Respiratory Tract Diseases
Lung Neoplasms
Paclitaxel
Lung Diseases
Tubulin Modulators
Non-small Cell Lung Cancer
Antineoplastic Agents, Phytogenic
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Antimitotic Agents
Carboplatin
Pharmacologic Actions
Carcinoma
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Paclitaxel
Therapeutic Uses
Lung Diseases
Tubulin Modulators
Antineoplastic Agents, Phytogenic
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009