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

Phase 2
Open (Enrolling)
Metastatic Cancer, Prostate Cancer

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Trial Information

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



- Compare the clinical efficacy of hormonal ablative therapy combined with doxorubicin
and zoledronate with or without strontium chloride Sr 89, in terms of progression-free
survival, in patients with androgen-dependent prostate cancer and bone metastases.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to the
number of bony metastases (≤ 6 versus > 6). Patients are randomized to 1 of 2 treatment

- Arm I: Patients receive hormonal ablative therapy comprising luteinizing
hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during
study treatment OR bilateral orchiectomy. Patients also receive doxorubicin
intravenously (IV) on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV
over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium
chloride Sr 89 IV over 1-2 minutes on day 1.

- Arm II: Patients receive hormonal ablative therapy, doxorubicin, and zoledronate as in
arm I.

In both arms, treatment continues in the absence of disease progression or unacceptable

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 80 patients (40 per treatment arm) will be accrued for this
study within 20 months.

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

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

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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to progression

Outcome Description:

Time to progression defined as the duration of time from start of treatment to disease progression.

Outcome Time Frame:

4 week intervals, up to 6 months of treatment, then follow up until disease progression

Safety Issue:


Principal Investigator

Shi-Ming Tu, MD

Investigator Role:

Study Chair

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

August 2004

Completion Date:

Related Keywords:

  • Metastatic Cancer
  • Prostate Cancer
  • recurrent prostate cancer
  • stage IV prostate cancer
  • bone metastases
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Prostatic Neoplasms



CCOP - Wichita Wichita, Kansas  67214-3882
M.D. Anderson Cancer Center at University of Texas Houston, Texas  77030
CCOP - Marshfield Clinic Research Foundation Marshfield, Wisconsin  54449
M.D. Anderson Cancer Center at Orlando Orlando, Florida  32806