Combined Modality Radioimmunotherapy For Hormone Refractory Metastatic Prostate Cancer With Two Cycles Of Escalating Dose 90Y-DOTA-Peptide-m170 And Fixed, Low Dose Paclitaxel With Blood Stem Cell Support And Cyclosporin For HAMA Suppression
- Determine the maximum tolerated dose of yttrium Y90 monoclonal antibody m170
administered with paclitaxel and cyclosporine followed by autologous peripheral blood
stem cell transplantation in patients with hormone-refractory metastatic prostate
- Determine the preliminary efficacy of this regimen in these patients.
OUTLINE: This is an open-label, dose-escalation study of yttrium Y 90 monoclonal antibody
m170 (Y90 MOAB m170). Patients are assigned to one of four cohorts.
After the first occurrence of hematologic dose-limiting toxicity in a patient, all
subsequent patients receive filgrastim (G-CSF) subcutaneously (SC) beginning 4 days prior to
undergoing apheresis and continuing until 6 million CD34+ cells/kg are collected. After 2
patients in a cohort group experience hematologic dose-limiting toxicity, subsequent
patients undergo autologous peripheral blood stem cell (PBSC) transplantation.
- Cohort I: Patients receive unlabeled monoclonal antibody (MOAB) m170 IV over 5 minutes
followed by a tracer dose of indium In 111 monoclonal antibody m170 (In111 MOAB m170)
IV over 5-10 minutes on day 0 and unlabeled MOAB m170 IV followed by Y90 MOAB m170 IV
on day 7. Patients also receive oral cyclosporine every 12 hours on days -3 to 25.
Patients may undergo autologous PBSC transplantation on day 21 and receive G-CSF SC
daily beginning on day 21 and continuing until blood counts recover.
- Cohort II: Patients receive treatment as in cohort I. Patients also receive paclitaxel
IV over 3 hours on day 9.
- Cohort III and IV: Patients receive treatment as in cohort I without In111 MOAB m170.
Patients also receive paclitaxel as in cohort II.
Cohorts of 3 to 6 patients receive escalating doses of Y90 MOAB m170 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity.
Patients are followed monthly for 3 months, every 3 months for 1 year, and then every 6
months for 1 year.
PROJECTED ACCRUAL: A total of 18-30 patients will be accrued for this study within 36
Masking: Open Label, Primary Purpose: Treatment
Carol M. Richman, MD
University of California, Davis
United States: Federal Government
|University of California Davis Cancer Center||Sacramento, California 95817|