Hormone Ablation Therapy, Doxorubicin, and Zoledronate With or Without Strontium 89 in Treating Patients With Androgen-Dependent Prostate Cancer and Bone Metastases

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00081159
• Other study ID #: 2003-0922
• Secondary ID: MDA-2003-0922NCI
• Status: Completed
• Phase: Phase 2
• First received: April 7, 2004
• Last updated: September 10, 2014
• Start date: July 2004

Study information

• Verified date: September 2014
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES:

Primary

• 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 arms.

• 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 toxicity.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Doxorubicin hydrochloride
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.
• Goserelin acetate

• Leuprolide acetate

• Zoledronic acid
4 mg given intravenously over 15 minutes every 28 days for a total of 6 doses.

Procedure:
• orchiectomy

Radiation:
• strontium chloride Sr
1 dose of strontium-89 (4 millicurie (mCi) total dose) administered intravenously on the first day of treatment

Locations

Country	Name	City	State
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	CCOP - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to progression	Time to progression defined as the duration of time from start of treatment to disease progression.	4 week intervals, up to 6 months of treatment, then follow up until disease progression	No
Secondary	Major bone scan response		Week 13	No

External Links

•   University of Texas MD Anderson Cancer Center Website