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
18 Years
N/A
Male
Prostate Cancer
Trial Information
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
OBJECTIVES:
- 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
cancer.
- 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
months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed hormone-refractory metastatic prostate
cancer
- Hormonal ablation (surgical or chemical) at least 3 months prior to study
- HAMA titer negative
- Less than 25% bone marrow involvement by metastatic prostate cancer
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 70-100%
Life expectancy:
- Not specified
Hematopoietic:
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,00/mm^3
- Hemoglobin at least 10.0 g/dL (without transfusion)
- No chronic transfusion requirement
Hepatic:
- Bilirubin no greater than 1.3 mg/dL
- AST no greater than 1.5 times normal
Renal:
- Creatinine less than 1.5 mg/dL
Cardiovascular:
- LVEF at least 50% by MUGA
- No disseminated intravascular coagulation
Pulmonary:
- FEV1 at least 65% of predicted
- FVC at least 65% of predicted
- Corrected DLCO at least 60%
Other:
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior murine protein (e.g., ProstaScint)
Chemotherapy:
- At least 4 weeks since prior standard dose chemotherapy
Endocrine therapy:
- See Disease Characteristics
Radiotherapy:
- At least 4 weeks since prior external beam radiotherapy
- No prior radiotherapy to no more than 25% of total skeleton
Surgery:
- See Disease Characteristics
Other:
- No concurrent oral anticoagulants (low dose coumadin for central line thrombosis
prophylaxis allowed)
- No concurrent chronic transfusions
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Carol M. Richman, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, Davis
Authority:
United States: Federal Government
Study ID:
CDR0000068364
NCT ID:
NCT00009750
Start Date:
March 2001
Completion Date:
Related Keywords:
- Prostate Cancer
- stage IV prostate cancer
- recurrent prostate cancer
- Prostatic Neoplasms
Name | Location |
|---|---|
| University of California Davis Cancer Center | Sacramento, California 95817 |
