Neoadjuvant Chemoradiotherapy With or Without Gefitinib in Treating Patients With Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells.
      Biological therapies such as gefitinib may interfere with the growth of the tumor cells and
      slow the growth of the tumor. Combining chemotherapy and radiation therapy with gefitinib
      before surgery may shrink the tumor so that it can be removed during surgery.

      PURPOSE: Phase I/II trial to compare the effectiveness of neoadjuvant chemoradiotherapy with
      or without gefitinib in treating patients who are undergoing surgery for stage III non-small
      cell lung cancer.
    

Detailed description: 
      OBJECTIVES: Phase I:

        -  Determine the tolerability and toxicity of gefitinib in combination with chest
           radiotherapy in patients with stage IIIA or stage IIIB non-small cell lung cancer.

      Phase II:

        -  Compare the pathologic response (complete response and rate of downstaging) in patients
           treated with neoadjuvant chemoradiotherapy with vs without gefitinib.

        -  Compare the feasibility and toxicity profile of these regimens in these patients.

        -  Compare the resection rates, time to progression, and overall survival of patients
           treated with these regimens.

        -  Correlate the percent decline in the fludeoxyglucose F 18 standardized uptake value as
           measured by position emission tomography with pathologic response at resection, time to
           progression, and overall survival in patients treated with these regimens.

      OUTLINE:

        -  Phase I: This is an open-label, nonrandomized study.

             -  Induction: Patients receive cisplatin IV over 60 minutes on day 1 and gemcitabine
                IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for a total of
                2 courses in the absence of disease progression or unacceptable toxicity.

             -  Consolidation: Within 3-4 weeks after the completion of induction therapy, patients
                undergo radiotherapy once daily 5 days a week for 5 weeks and receive oral
                gefitinib once daily concurrently.

      A cohort of 3-6 patients receives consolidation chemoradiotherapy. If 2 of 6 patients
      experience dose-limiting toxicity, gefitinib is deleted from consolidation therapy in phase
      II arm II.

        -  Surgery: Patients without disease progression after consolidation therapy undergo
           thoracotomy within 3-5 weeks after consolidation.

        -  Maintenance: Beginning 2-4 weeks after surgery, patients receive oral gefitinib once
           daily for 6 months in the absence of disease progression.

             -  Phase II: This is a randomized study. Patients are randomized to 1 of 2 treatment
                arms.

        -  Arm I: Patients receive induction and consolidation therapy (with the exception of
           gefitinib) as in phase I. Patients also receive docetaxel IV over 60 minutes
           concurrently with radiotherapy during consolidation. Patients undergo surgery as in
           phase I.

        -  Arm II: Patients receive therapy (including gefitinib) as in phase I. Patients also
           receive docetaxel IV over 60 minutes concurrently with radiotherapy during
           consolidation.

      Patients are followed every 6-8 weeks for the first 12 months and then every 4-6 months
      thereafter.

      PROJECTED ACCRUAL: A total of 43-80 patients (3-6 patients for phase I and 40-74 patients
      [20-37 per treatment arm] for phase II) will be accrued for this study.
    

Intervention name(s): cisplatin; docetaxel; gefitinib; gemcitabine hydrochloride; conventional surgery; neoadjuvant therapy; radiation therapy
Intervention type(s): Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention MeSH terms: Gemcitabine; Docetaxel; Gefitinib
Allocation: Randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer