Hormone Ablation Therapy, Doxorubicin, and Zoledronate With or Without Strontium 89 in Treating Patients With Androgen-Dependent Prostate Cancer and Bone Metastases
Condition: Metastatic Cancer; Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Doxorubicin hydrochloride; Goserelin acetate; Leuprolide acetate; Zoledronic acid; orchiectomy; strontium chloride Sr
Intervention description: Doxorubicin 20 mg/m^2 is administered intravenously either over 15 to 30 minutes via a peripheral line or over 24 hours via a central line on days 1, 8, and 15 every 28 days for 2 cycles.; 4 mg given intravenously over 15 minutes every 28 days for a total of 6 doses.; 1 dose of strontium-89 (4 millicurie (mCi) total dose) administered intravenously on the first day of treatment
Intervention MeSH terms: Zoledronic Acid; Doxorubicin; Liposomal doxorubicin; Leuprolide; Goserelin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: Male
Healthy volunteers: No
Keywords: recurrent prostate cancer; stage IV prostate cancer; bone metastases

Summary:

      RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as
      goserelin and leuprolide may fight prostate cancer by stopping the adrenal glands from
      producing androgens. Drugs used in chemotherapy such as doxorubicin work in different ways to
      stop tumor cells from dividing so they stop growing or die. Zoledronate may prevent bone loss
      and stop the growth of tumor cells in bone. Radioactive substances such as strontium-89 may
      relieve bone pain associated with prostate cancer. It is not yet known whether hormone
      (androgen) ablation therapy and chemotherapy combined with zoledronate is more effective with
      or without strontium-89 in treating prostate cancer and bone metastases.

      PURPOSE: This randomized phase II trial is studying giving hormone ablation therapy,
      doxorubicin, and zoledronate together with strontium-89 to see how well it works compared to
      hormone ablation therapy, doxorubicin, and zoledronate alone in treating patients with
      androgen-dependent prostate cancer and bone metastases.
    

Eligibility criteria:

        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.