Combination Chemotherapy, Bev, RT, and Erlotinib in Treating Patients With Stage III 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, such as carboplatin and paclitaxel, 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 bevacizumab, 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. Bevacizumab may also stop the
      growth of non-small cell lung cancer by blocking blood flow to the tumor. Radiation therapy
      uses high energy x-rays to kill tumor cells. Erlotinib may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together
      with bevacizumab, radiation therapy, and erlotinib may kill more tumor cells.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of bevacizumab and
      erlotinib when given together with combination chemotherapy and radiation therapy and to see
      how well they work in treating patients with stage III non-small cell lung cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the maximum tolerated dose of bevacizumab and erlotinib hydrochloride when
           given together with carboplatin, paclitaxel, and thoracic conformal radiotherapy in
           patients with stage IIIA or IIIB non-small cell lung cancer. (Phase I [closed to accrual
           as of 1/3/2008])

        -  Determine the safety and toxicity profile of this regimen in these patients. (Phase I
           [closed to accrual as of 1/3/2008])

        -  Determine the progression-free survival of patients treated with induction therapy
           comprising carboplatin, paclitaxel, and bevacizumab followed by chemoradiotherapy
           comprising thoracic conformal radiotherapy, carboplatin, paclitaxel, bevacizumab, and
           erlotinib hydrochloride and consolidation therapy comprising bevacizumab and erlotinib
           hydrochloride. (Phase II)

        -  Determine the overall toxicity profile of this regimen in these patients. (Phase II)

      Secondary

        -  Determine the response rate in patients treated with induction therapy comprising
           carboplatin, paclitaxel, and bevacizumab. (Phase I[closed to accrual as of 1/3/2008] and
           II)

        -  Determine the toxicity profile of induction therapy in these patients. (Phase I [closed
           to accrual as of 1/3/2008] and II)

        -  Determine the overall response rate and survival profile in patients treated with this
           regimen. (Phase I [closed to accrual as of 1/3/2008] and II)

        -  Determine the feasibility and tolerability of administering consolidation therapy
           comprising erlotinib hydrochloride and bevacizumab after treatment with combined
           modality therapy (induction therapy and chemoradiotherapy) in these patients. (Phase I
           [closed to accrual as of 1/3/2008] and II)

        -  Collect tumor and blood samples from these patients for future analysis of correlation
           between molecular markers and clinical benefit. (Phase I [closed to accrual as of
           1/3/2008] and II)

      OUTLINE: This is a nonrandomized, open-label, controlled, phase I (closed to accrual as of
      1/3/2008), dose-escalation study of bevacizumab and erlotinib hydrochloride, followed by a
      phase II study.

        -  Phase I (closed to accrual as of 1/3/2008):

             -  Induction therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over
                15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats
                every 21 days for 2 courses. Patients with stable or responding disease proceed to
                chemoradiotherapy.

             -  Chemoradiotherapy: Patients receive chemoradiotherapy according to their assigned
                dose cohort:

                  -  Cohort 1: Patients undergo thoracic conformal radiotherapy (TCRT) on days 1-5,
                     8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. Patients also receive carboplatin
                     IV and paclitaxel IV on days 1, 8, 15, 22, 29, 36, and 43 and bevacizumab IV
                     over 30-90 minutes on days 1, 15, 29, and 43.

                  -  Cohort 2: Patients undergo TCRT and receive carboplatin, paclitaxel, and
                     bevacizumab as in cohort 1. Patients also receive oral erlotinib hydrochloride
                     on days 2-5, 9-12, 16-19, 23-26, 30-33, 37-40, and 44-47.

                  -  Cohort 3: Patients undergo TCRT and receive carboplatin, paclitaxel, and
                     bevacizumab as in cohort 1. Patients also receive higher doses of oral
                     erlotinib hydrochloride on days 2-5, 9-12, 16-19, 23-26, 30-33, 37-40, and
                     44-47.

      Cohorts of 5 patients receive chemoradiotherapy as described above until the maximum
      tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
      (with grade 4 toxicity) or 3 (with grade 3 toxicity) of 5 patients experience dose-limiting
      toxicity.

      Three to 6 weeks after completion of chemoradiotherapy, patients proceed to consolidation
      therapy.

        -  Consolidation therapy: Patients receive bevacizumab IV on day 1 and oral erlotinib
           hydrochloride on days 1-21. Treatment repeats every 21 days for up to 6 courses in the
           absence of disease progression or unacceptable toxicity.

             -  Phase II:

        -  Induction therapy: Patients receive induction therapy as in phase I (closed to accrual
           as of 1/3/2008).

        -  Chemoradiotherapy: Patients undergo TCRT and receive carboplatin and paclitaxel as in
           phase I (closed to accrual as of 1/3/2008). Patients also receive bevacizumab and
           erlotinib hydrochloride as in phase I (closed to accrual as of 1/3/2008) at the MTD/drug
           combination determined in phase I (closed to accrual as of 1/3/2008).

        -  Consolidation therapy: Patients receive consolidation therapy as in phase I (closed to
           accrual as of 1/3/2008).

      Tumor tissue and peripheral blood is collected at baseline for future correlative and
      biomarker studies.

      After completion of study therapy, patients are followed every 2 months for 2 years, every 4
      months for 2 years, every 6 months for 2 years, and then annually thereafter.
    

Intervention name(s): bevacizumab; carboplatin; erlotinib hydrochloride; paclitaxel; 3-dimensional conformal radiation therapy
Intervention type(s): Biological; Drug; Drug; Drug; Radiation
Intervention description(s): Given IV; Given IV; Given orally; Given IV; Given 5 days a week for 7 weeks
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Erlotinib Hydrochloride
Allocation: Non-Randomized
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; squamous cell lung cancer