Samarium-153 With Neoadjuvant Hormonal and Radiation Therapy for Locally Advanced Prostate Cancer

Phase 1

Completed

Conditions: Prostate Cancer

Interventions: Drug: Samarium-153
Drug: Total Androgen Suppression (TAS) with Bicalutamide
Drug: Total androgen suppression (TAS) with Goserelin Acetate
Device: Radiation Therapy

Registration Number: NCT00328614

Lead Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Brief Summary: The 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 32

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Samarium-153 (1.0 mCi/kg)	Samarium-153	Cohort 4: Patients receive 1.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (2.0 mCi/kg)	Samarium-153	Cohort 6: Patients receive 2.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.25 mCi/kg)	Total androgen suppression (TAS) with Goserelin Acetate	Cohort 1: Patients receive 0.25 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.25 mCi/kg)	Radiation Therapy	Cohort 1: Patients receive 0.25 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.5 mCi/kg)	Radiation Therapy	Cohort 2: Patients receive 0.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (1.0 mCi/kg)	Total androgen suppression (TAS) with Goserelin Acetate	Cohort 4: Patients receive 1.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.75 mCi/kg)	Total androgen suppression (TAS) with Goserelin Acetate	Cohort 3: Patients receive 0.75 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.75 mCi/kg)	Radiation Therapy	Cohort 3: Patients receive 0.75 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (1.0 mCi/kg)	Radiation Therapy	Cohort 4: Patients receive 1.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (1.5 mCi/kg)	Total Androgen Suppression (TAS) with Bicalutamide	Cohort 5: Patients receive 1.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (1.5 mCi/kg)	Total androgen suppression (TAS) with Goserelin Acetate	Cohort 5: Patients receive 1.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (1.5 mCi/kg)	Radiation Therapy	Cohort 5: Patients receive 1.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (2.0 mCi/kg)	Total Androgen Suppression (TAS) with Bicalutamide	Cohort 6: Patients receive 2.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (2.0 mCi/kg)	Total androgen suppression (TAS) with Goserelin Acetate	Cohort 6: Patients receive 2.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (2.0 mCi/kg)	Radiation Therapy	Cohort 6: Patients receive 2.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.25 mCi/kg)	Total Androgen Suppression (TAS) with Bicalutamide	Cohort 1: Patients receive 0.25 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.5 mCi/kg)	Total Androgen Suppression (TAS) with Bicalutamide	Cohort 2: Patients receive 0.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.5 mCi/kg)	Total androgen suppression (TAS) with Goserelin Acetate	Cohort 2: Patients receive 0.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.75 mCi/kg)	Total Androgen Suppression (TAS) with Bicalutamide	Cohort 3: Patients receive 0.75 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (1.0 mCi/kg)	Total Androgen Suppression (TAS) with Bicalutamide	Cohort 4: Patients receive 1.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.25 mCi/kg)	Samarium-153	Cohort 1: Patients receive 0.25 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.5 mCi/kg)	Samarium-153	Cohort 2: Patients receive 0.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (0.75 mCi/kg)	Samarium-153	Cohort 3: Patients receive 0.75 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy
Samarium-153 (1.5 mCi/kg)	Samarium-153	Cohort 5: Patients receive 1.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose of Samarium-153	5 months (1 month HT, administration of drug, 4 months HT and RT)	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.

Secondary Outcome Measures