Title
Samarium-153 With Neoadjuvant Hormonal and Radiation Therapy for Locally Advanced Prostate Cancer
A Phase I Pilot Study of Samarium-153 Combined With Neoadjuvant Hormonal Therapy and Radiation Therapy in Men With Locally Advanced Prostate Cancer
Phase
Phase 1Lead Sponsor
Thomas Jefferson UniversityStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Prostate CancerIntervention/Treatment
goserelin bicalutamide sm-153 ...Study Participants
32The purpose of this study is to determine the safety and effectiveness of Samarium-153 when given in combination with hormonal and external beam radiation therapy in men with high risk prostate cancer.
The likelihood of prostate cancer cells metastasizing to bone has an early and important influence on the natural history of prostate cancer. Bone-targeted therapy, when given sequentially with hormonal therapy (androgen suppression) and radiation therapy, prolongs the progression of the disease in clinically non-metastatic prostate cancer patients.
The use of Samarium-153 EDTMP in conjunction with hormonal therapy and external beam radiation therapy has never been previously evaluated in high risk clinically localized prostate cancer. Many patients with high-risk prostate cancer develop progressive disease within 2 years of therapy indicating that subclinical metastatic disease may be present at the time of initial diagnosis. In these high-risk patients, there may be a therapeutic benefit of combining hormonal therapy with external beam radiation therapy and Samarium-153 EDTMP to treat localized and subclinical bony disease, respectively.
Samarium-153 will be administered as a single dose after one month of hormonal therapy. The dose level of Samarium-153 may change to determine maximum tolerated dose (MTD).
Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation.
Patients will receive 5 months of total androgen suppression (TAS) consisting of Zoladex and Casodex. Total androgen suppression will begin 3 months prior to initiation of irradiation.
Radiation therapy will begin 3 months following the initiation of hormone administration. Daily tumor doses will be given 5 days per week for 7-8 weeks.
Cohort 1: Patients receive 0.25 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Cohort 2: Patients receive 0.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Cohort 3: Patients receive 0.75 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Cohort 4: Patients receive 1.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Cohort 5: Patients receive 1.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Cohort 6: Patients receive 2.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Inclusion Criteria: PSA 20-150 and Gleason score greater than or equal to 7 or clinical stage greater than or equal to T2, Gleason greater than or equal to 8, PSA less than or equal to 150 Pathologically positive lymph nodes Pretreatment must be prior to study entry and prior to any hormonal therapy Zubrod 0-1 Adequate hematologic function Exclusion Criteria: Patients with PSA equal to or greater than 150 Neuroendocrine features on histologic examination Radiologic evidence of metastatic disease Previous malignancy within last 5 years Prior pelvic radiation therapy or orchiectomy
| Event Type | Organ System | Event Term | Samarium-153 (0.25 mCi/kg) | Samarium-153 (0.5 mCi/kg) | Samarium-153 (0.75 mCi/kg) | Samarium-153 (1.0 mCi/kg) | Samarium-153 (1.5 mCi/kg) | Samarium-153 (2.0 mCi/kg) |
|---|
To determine the maximum tolerated dose (MTD) of Samarium as adjuvant to combined hormonal therapy (HT) and external beam radiation therapy (RT). Dose levels: Dose I: 0.25 mCi/kg IV Dose II: 0.5 mCi/kg IV Dose III: 0.75 mCi/kg IV Dose IV: 1.0 mCi/kg IV Dose V: 1.5 mCi/kg IV Dose VI: 2.0 mCi/kg IV Dose-limiting toxicity will be defined as Grade 3 hematologic toxicity per NCI Common Toxicity Criteria. The maximally tolerated dose (MTD) will then be the last dose studied or the previous dose, based on clinical judgment of the degree of toxicity seen at the last dose.
