A Randomized Phase II Study Of Bone-Targeted Therapy In Advanced Androgen-Dependent Prostate Cancer

Study start date: July 1, 2004

Inclusion Criteria: 1. Histologically or cytologically confirmed prostate carcinoma. 2. Osteoblastic metastases on bone scan or computed tomography (CT) scan. 3. Initiation of hormonal ablative therapy within 3 months of registration. 4. Prior neoadjuvant, concurrent, or intermittent hormonal ablative therapy of less than 3 years duration and completed at least 3 years prior to entry into this study. 5. The Eastern Cooperative Oncology Group (ECOG) performance status \<3 (Karnofsky \>40%) 6. Patients must have normal organ and marrow function as defined: leukocytes: \>3,000/mL; absolute neutrophil count: \>1,500/mL; platelets: \>100,000/mL; total bilirubin within normal institutional limits; alanine transaminase (ALT)(SGPT)/aspartate aminotransferase (AST)(SGOT): \<2.5 \* institutional upper limit of normal; creatinine: \< or = 3.0; left ventricular ejection fraction: \>45% 7. The effects of strontium-89 and zoledronic acid on the developing human fetus at the recommended therapeutic dose are unknown. Even though all patients are castrated during this study, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should the spouse of a patient become pregnant or suspect she is pregnant while participating in this study, she/he should inform the treating physician immediately. 8. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: 1. More than one prior chemotherapy regimen. Prior doxorubicin treatment is permitted. However patient's with \>250 mg/m2 cumulative dosage are excluded. 2. Prior radioisotope treatment consisting of strontium-89 or samarium-153. 3. Zoledronic acid treatment for more than 3 months duration prior to registration. Other bisphosphonate treatments are permitted. 4. Corrected serum calcium level less than 8 mg/dL. 5. Patients may not be receiving any other investigational agents. 6. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. 7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to zoledronic acid or other agents used in the study 8. Patients with the following atypical presentations should have a biopsy: those with small cell carcinoma, purely lytic bone metastases, or bulky (i.e. 5 cm) visceral or nodal disease in the absence of bone involvement are not eligible. 9. Symptomatic bulky lymphadenopathy causing scrotal or pedal edema or significant local invasive disease in bladder invasion. 10. History of other malignancies other than nonmelanoma skin cancer, unless in complete remission and off therapy for that disease for at least 5 years. 11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 12. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with strontium-89 or other agents administered during the study. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated. 13. Evidence or suspicion of myelodysplastic syndrome by complete blood test (CBC) must be confirmed by bone marrow biopsy. 14. Untreated symptomatic spinal cord compressions.