Iodine I 131 Monoclonal Antibody 3F8 and Bevacizumab in Treating Patients With Relapsed or Refractory Neuroblastoma
RATIONALE: Monoclonal antibodies, such as iodine I 131 monoclonal antibody 3F8 and 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 neuroblastoma by blocking blood flow to the tumor. Giving iodine I 131 monoclonal antibody 3F8 together with bevacizumab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of iodine I 131 monoclonal antibody 3F8 when given together with bevacizumab in treating patients with relapsed or refractory neuroblastoma.
Procedure: autologous hematopoietic stem cell transplantation
Radiation: iodine I 131 monoclonal antibody 3F8
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Combination of Targeted I -3F8-Mediated Radioimmunotherapy and Bevacizumab in Patients With Relapsed or Refractory Neuroblastoma: A Phase I Study|
- Maximum tolerated dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2006|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: Iodine I 131 Monoclonal Antibody 3F8 and Bevacizumab
Patients will be administered a therapeutic doses of intravenous (IV) 131I-3F8 given in a single dose per the dose escalation regimen on day 0 of study. This will be followed by blood draws for pharmacokinetic and dosimetry studies and by gamma camera scan, where feasible. Bevacizumab will be administered at a fixed dose of 15mg/kg on days 1 and 15. Thyroid protection is commenced 10 days prior to administration of 131I-3F8 and continued for 28 days after the therapeutic dose of 131I-3F8. ASCR will be carried out if ANC < 500/ul on day 28 (blood radioactivity will be confirmed to be <1 uCi/ml prior to ASCR). ASCR will be carried out sooner in the case of life-threatening infection in the setting of neutropenia (ANC<500). G-CSF can be used to maintain ANC>500/ul but should not be used for 24 hours immediately before and after ASCR. Blood product support will be provided with platelet and red cell transfusions as required.
|Biological: bevacizumab Biological: filgrastim Procedure: autologous hematopoietic stem cell transplantation Radiation: iodine I 131 monoclonal antibody 3F8|
- Determine the toxicity of iodine I 131 monoclonal antibody 3F8 (^131I-3F8) and bevacizumab in patients with relapsed or refractory neuroblastoma.
- Determine the hematopoietic recovery after autologous stem cell rescue in patients treated with this regimen.
- Determine the clinical response rates in patients treated with this regimen.
- Assess whole body dosimetry for ^131I-3F8.
- Assess tumor targeting of ^131I-3F8 before and after bevacizumab.
OUTLINE: This is a dose-escalation study of iodine I 131 monoclonal antibody 3F8 (^131I-3F8).
Patients receive ^131I-3F8 IV over 20-30 minutes on day 0 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 courses. Patients whose blood counts do not recover and whose human antimouse antibody (HAMA) titer < 1,000 U/mL after course 1 receive one dose of ^131I-3F8 alone followed by autologous stem cell rescue (ASCR) and filgrastim (G-CSF). Patients whose blood counts do not recover and whose HAMA titer ≥ 1,000 U/mL after course 1 undergo ASCR followed by G-CSF. Patients whose blood counts recover and whose HAMA titer < 1,000 U/mL after course 1 receive 3 more courses of ^131I-3F8 and bevacizumab in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of ^131I-3F8 and bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
After completion of study treatment, patients are followed at 3-4 weeks and then every 3-6 months thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00450827
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Study Chair:||Shakeel Modak, MD||Memorial Sloan-Kettering Cancer Center|
|Principal Investigator:||Nai-Kong V. Cheung, MD, PhD||Memorial Sloan-Kettering Cancer Center|