Nelfinavir, Radiation Therapy, Cisplatin, and Etoposide in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Nelfinavir may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells.
      Nelfinavir may make tumor cells more sensitive to radiation therapy. Drugs used in
      chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of
      tumor cells, either by killing the cells or by stopping them from dividing. Giving nelfinavir
      together with radiation therapy, cisplatin, and etoposide may kill more tumor cells.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of nelfinavir when
      given together with radiation therapy, cisplatin, and etoposide and to see how well they work
      in treating patients with stage III non-small cell lung cancer that cannot be removed by
      surgery.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To determine the dose-limiting toxicities, maximum tolerated dose, and recommended phase
           II dose of nelfinavir mesylate when administered in combination with concurrent thoracic
           radiotherapy, cisplatin, and etoposide in patients with unresectable locally advanced
           non-small cell lung cancer.

      Secondary

        -  To determine the tumor response at 3 months after completion of treatment as measured by
           RECIST criteria.

        -  To assess the inhibition of p-Akt in primary tumor or pathologic lymph nodes and in
           peripheral blood lymphocytes after 5-10 days of treatment with nelfinavir mesylate.

        -  To determine the median overall survival (OS) of patients treated with this regimen.

        -  To compare the observed median OS of these patients with the historical median OS of 17
           months.

      OUTLINE: This is a phase I, dose-escalation study of nelfinavir mesylate followed by a phase
      II study.

        -  Phase I: Patients receive oral nelfinavir mesylate twice daily beginning 1-2 weeks
           before the initiation of chemoradiotherapy and continuing until the completion of
           radiotherapy. Patients undergo thoracic radiotherapy once daily 5 days a week for 7-8
           weeks. Patients also receive cisplatin IV on days 1, 8, 29, and 36 and etoposide IV on
           days 1-5 and 29-33. After completion of chemoradiotherapy, patients receive two
           additional courses of cisplatin and etoposide.

        -  Phase II: Patients receive nelfinavir mesylate at the maximum tolerated dose determined
           in phase I and concurrent chemoradiotherapy as in phase I.

      Patients undergo blood sample collection periodically for correlative laboratory studies.
      Patients treated in the phase II portion of the study and those with primary tumors or
      pathologic lymph nodes easily accessible by core biopsy or mediastinoscopy also undergo tumor
      tissue biopsies. Blood and tumor tissue samples are analyzed for expression of molecular
      markers (total Akt and p-Akt ) by immunohistochemistry. The molecular markers are correlated
      with treatment response.

      After completion of study treatment, patients are followed at 3, 6, and 12 months.
    

Intervention name(s): cisplatin; etoposide; nelfinavir mesylate; protein expression analysis; immunohistochemistry staining method; laboratory biomarker analysis; biopsy; radiation therapy
Intervention type(s): Drug; Drug; Drug; Genetic; Other; Other; Procedure; Radiation
Intervention MeSH terms: Nelfinavir; Etoposide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; recurrent non-small cell lung cancer