Combination Chemotherapy and Bevacizumab in Treating Patients With Advanced Neuroendocrine Tumors
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, 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 neuroendocrine tumors by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects of giving combination chemotherapy together with bevacizumab and to see how well it works in treating patients with advanced neuroendocrine tumors.
Gastrointestinal Carcinoid Tumor
Islet Cell Tumor
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot Study of FOLFOX in Combination With Bevacizumab in Patients With Advanced Neuroendocrine Tumors|
- The rate of discontinuation due to adverse events (besides neuropathy) possibly related to study treatment. [ Time Frame: During study treatment period, expected to be up to 2 - 18 months; Post-study survival follow-up period, up to 2-8 years ] [ Designated as safety issue: Yes ]Carcinoid Tumors: 2-8 months median time to progression Pancreatic Neuroendocrine Tumors: 15-18 months median time to progression Poorly Differentiated Neuroendocrine Tumors: 9-11 months median time to progression
- Objective radiographic response rate [ Time Frame: During study treatment period, expected to be up to 2 - 18 months; Post-study survival follow-up period, up to 2-8 years ] [ Designated as safety issue: No ]Carcinoid Tumors: 2-8 months median time to progression Pancreatic Neuroendocrine Tumors: 15-18 months median time to progression Poorly Differentiated Neuroendocrine Tumors: 9-11 months median time to progression
- Overall survival [ Time Frame: until death ] [ Designated as safety issue: No ]
- Time to treatment failure [ Time Frame: until patient went off study ] [ Designated as safety issue: No ]
- Time to progression [ Time Frame: Until patient went off study and until death ] [ Designated as safety issue: No ]
- Biochemical marker response [ Time Frame: Until patient went off study ] [ Designated as safety issue: No ]
|Study Start Date:||June 2005|
|Estimated Study Completion Date:||June 2016|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Experimental: FOLFOX with Bevacizumab
Starting on Day 1, administered every two weeks:
5-fluorouracil: 2400 mg/ m2 CIV; over 46-48 hours Leucovorin: 200 mg/ m2; over 2 hours Oxaliplatin : 85 mg/m2; over 2 hours Bevacizumab: 5 mg/kg IV over 30-90 minutes
5mg/kg IV q 2 wk on day 1. Initial study drug dose will be delivered over 90 +/- 15 minutes x1. If the first infusion is tolerated without fever/chills, the second infusion may be delivered over 60 +/- 10 minutes. If 60 minutes infusion is well tolerated, all subsequent infusions maybe be delivered over 30 +/- 10 minutes.
Other Name: AvastinDrug: 5-fluorouracil
2400mg/m2 CIV over 46-48 hours D1-2 q2 weeks.
Other Names:Drug: leucovorin
200mg/m2 IV q2 wk on day 1 over a 2-hour period.
Other Name: Folinic acidDrug: oxaliplatin
200mg/m2 IV q 2 wk on day 1 over a 2-hour period
Other Name: Eloxatin
- Determine the safety of fluorouracil, leucovorin calcium, and oxaliplatin (FOLFOX) with bevacizumab in patients with advanced neuroendocrine tumors.
- Determine the best overall response rate in patients treated with this regimen.
- Determine the overall survival of patients treated with this regimen.
- Determine the time to treatment failure and progression in patients treated with this regimen.
- Determine the biochemical marker response in patients treated with this regimen.
OUTLINE: This is an open-label, pilot study. Patients are stratified according to tumor type (carcinoid vs islet cell vs poorly differentiated neuroendocrine).
Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46-48 hours beginning on day 1. Patients also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for up to 26 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 39-102 patients (13-34 per stratum) will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00227617
|United States, California|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94115|
|Kaiser Permanente Medical Center - Vallejo|
|Vallejo, California, United States, 94589|
|Principal Investigator:||Emily K. Bergsland, MD||University of California, San Francisco|