RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine, carboplatin, and paclitaxel and 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 tumor cells by blocking blood flow to the tumor. Giving hydroxychloroquine together with carboplatin, paclitaxel and bevacizumab may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of hydroxychloroquine when given together with carboplatin, paclitaxel, and bevacizumab and to see how well they work in treating patients with recurrent advanced non-small cell lung cancer.
Primary Outcome Measures:
- Recommended phase II dose of hydroxychloroquine and carboplatin when administered with paclitaxel and bevacizumab (phase I) [ Designated as safety issue: No ]
- Overall response (phase II) [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Time to progression (phase II) [ Designated as safety issue: No ]
- Progression-free survival at 1 year (phase II) [ Designated as safety issue: No ]
- Overall survival (phase II) [ Designated as safety issue: No ]
Estimated Enrollment: |
37 |
Study Start Date: |
June 2008 |
Estimated Primary Completion Date: |
August 2011 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
- To determine the recommended phase II dose of hydroxychloroquine and carboplatin in combination with paclitaxel and bevacizumab in patients with advanced recurrent non-small cell lung cancer. (Phase I)
- To assess the antitumor activity, as measured by tumor response rate, of this regimen in these patients. (Phase II)
Secondary
- To measure time to progression, progression-free survival, and overall survival of these patients.
- To assess the incidence of toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study. This is a phase I, dose-escalation study of carboplatin and hydroxychloroquine followed by a phase II study.
Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 90 minutes on day 1 and oral hydroxychloroquine on days 1-21. Treatment repeats every 21 days for a total of 4 courses. Patients then receive bevacizumab IV over 30-90 minutes every 21 days and oral hydroxychloroquine daily for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed every 6 months.