Combination of Targeted I -3F8-Mediated Radioimmunotherapy and Bevacizumab in Patients With Relapsed or Refractory Neuroblastoma: A Phase I Study
- 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
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
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD)
Shakeel Modak, MD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|