Prostate Cancer
Conditions
Keywords
Locally advanced prostate cancer, positive lymph nodes
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.
Interventions
DRUGSamarium-153
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).
DRUGTotal Androgen Suppression (TAS) with Bicalutamide
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.
DRUGTotal androgen suppression (TAS) with Goserelin Acetate
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.
DEVICERadiation Therapy
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.
Sponsors
Cytogen Corporation
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Samarium-153 (0.25 mCi/kg) Cohort 1: Patients receive 0.25 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy | 4 |
| Samarium-153 (0.5 mCi/kg) Cohort 2: Patients receive 0.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy | 4 |
| Samarium-153 (0.75 mCi/kg) Cohort 3: Patients receive 0.75 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy | 6 |
| Samarium-153 (1.0 mCi/kg) Cohort 4: Patients receive 1.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy | 6 |
| Samarium-153 (1.5 mCi/kg) Cohort 5: Patients receive 1.5 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy | 6 |
| Samarium-153 (2.0 mCi/kg) Cohort 6: Patients receive 2.0 mCi/kg of Samarium-153, hormonal therapy, and radiation therapy | 6 |
| Total | 32 |
Baseline characteristics
| Characteristic | Samarium-153 (0.5 mCi/kg) | Samarium-153 (0.75 mCi/kg) | Samarium-153 (1.0 mCi/kg) | Samarium-153 (0.25 mCi/kg) | Samarium-153 (1.5 mCi/kg) | Samarium-153 (2.0 mCi/kg) | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 4 Participants | 22 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 3 Participants | 2 Participants | 10 Participants |
| Age, Continuous | 65.10 years STANDARD_DEVIATION 9.78 | 65.58 years STANDARD_DEVIATION 10 | 69.46 years STANDARD_DEVIATION 8.04 | 66.97 years STANDARD_DEVIATION 1.37 | 68.00 years STANDARD_DEVIATION 13.13 | 66.19 years STANDARD_DEVIATION 8.02 | 66.99 years STANDARD_DEVIATION 8.75 |
| Region of Enrollment United States | 4 participants | 6 participants | 6 participants | 4 participants | 6 participants | 6 participants | 32 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 6 Participants | 4 Participants | 6 Participants | 6 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 6 |
| serious Total, serious adverse events | 0 / 4 | 1 / 4 | 1 / 6 | 2 / 5 | 3 / 5 | 5 / 6 |
Outcome results
Primary
Maximum Tolerated Dose of Samarium-153
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.
Time frame: 5 months (1 month HT, administration of drug, 4 months HT and RT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Samarium-153 | Maximum Tolerated Dose of Samarium-153 | 2.0 mCi/kg |