High-Dose or Standard-Dose Radiation Therapy and Chemotherapy With or Without Cetuximab in Treating Patients With Newly Diagnosed Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

Assistant Professor
Department of Radiation Oncology

Trial Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. 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. It is not yet known whether high-dose radiation therapy is more effective than standard-dose radiation therapy when given together with combination chemotherapy with or without cetuximab in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying high-dose or standard-dose radiation therapy given together with chemotherapy with or without cetuximab to see how well they work in treating patients with newly diagnosed stage III non-small cell lung cancer that cannot be removed by surgery.

Eligibility

• 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
            - N2 or N3 disease and an undetectable NSCLC primary tumor allowed
      - Unresectable or inoperable disease
• No distant metastases
• 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

• 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

• 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

Detailed Description

Patients will be randomly assigned (have an equal chance of being placed) to one of four treatment groups.

Patients in group one will have standard-dose radiation therapy 5 days a week for 6 weeks. They will also receive a 1-hour infusion of paclitaxel and an infusion of carboplatin once a week in weeks 1-4 and 6 and twice in week 5.

Patients in group two will undergo high-dose radiation therapy 5 days a week for 7 ½ weeks. They will also receive a 1-hour infusion of paclitaxel and an infusion of carboplatin once a week in weeks 1-4 and 6 and twice in week 5. Patients will receive additional paclitaxel and carboplatin in weeks 10 and 13.

Patients in group three will undergo standard-dose radiation therapy 5 days a week for 6 weeks. They will also receive a 1-hour infusion of cetuximab, paclitaxel, and carboplatin once a week in weeks 1-4 and 6 and twice in week 5. Patients will receive additional cetuximab, paclitaxel, and carboplatin in weeks 11 and 14.

Patients in group four will undergo high-dose radiation therapy 5 days a week for 7 ½ weeks. They will also receive a 1-hour infusion of cetuximab, paclitaxel, and carboplatin once a week in weeks 1-4 and 6 and twice in week 5. Patients will receive additional cetuximab, paclitaxel, and carboplatin in weeks 12 and 15.

Patients may undergo tumor tissue, blood, and urine collection periodically for laboratory studies.

Quality of life may be assessed at the beginning of the study and periodically during the study. After finishing treatment, patients will be evaluated periodically for 5 years and once a year thereafter.

Final eligibility is determined by the health professionals conducting the trial and the protocol approved by the Committee on Human Resources (CHR) at the University of California, San Francisco (UCSF). The Patient Consent Form for this trial is available upon request. For more information about this trial, please see the full posting at ClinicalTrials.gov.

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