Hormone Ablation Therapy, Doxorubicin, and Zoledronate With or Without Strontium 89 in Treating Patients With Androgen-Dependent Prostate Cancer and Bone Metastases
A Randomized Phase II Study Of Bone-Targeted Therapy In Advanced Androgen-Dependent Prostate Cancer
6 other identifiers
interventional
80
1 country
4
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2004
Longer than P75 for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 7, 2004
CompletedFirst Posted
Study publicly available on registry
April 8, 2004
CompletedStudy Start
First participant enrolled
July 1, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2014
CompletedResults Posted
Study results publicly available
November 10, 2016
CompletedNovember 10, 2016
September 1, 2016
10.2 years
April 7, 2004
September 22, 2016
September 22, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
Study's primary endpoint of PFS duration/time to progression was defined as the time from the date of randomization to the date of first evidence of disease progression or patient death. Prostate-specific antigen (PSA) progression is usually the first evidence of progression. PSA progression is defined as a 25% increase over the baseline or the nadir provided that the increase is a minimum of 1 ng/ml.
Up to 90 months with evaulation in 4 week intervals for up to 6 months of treatment, then follow up until disease progression
Secondary Outcomes (1)
Major Bone Scan Response
Week 13
Other Outcomes (1)
Overall Survival (OS)
Up to 90 months
Study Arms (2)
HAT, Doxorubicin, Zoledronate + Strontium chloride
EXPERIMENTALArm I: Hormonal ablative therapy (HAT) comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin 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.
HAT, Doxorubicin + Zoledronate
EXPERIMENTALArm II: HAT, doxorubicin, and zoledronate as in arm I. HAT comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin 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.
Interventions
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
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed prostate carcinoma.
- Osteoblastic metastases on bone scan or computed tomography (CT) scan.
- Initiation of hormonal ablative therapy within 3 months of registration.
- 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.
- The Eastern Cooperative Oncology Group (ECOG) performance status \<3 (Karnofsky \>40%)
- 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%
- 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.
- Ability to understand and the willingness to sign a written informed consent document.
You may not qualify if:
- More than one prior chemotherapy regimen. Prior doxorubicin treatment is permitted. However patient's with \>250 mg/m2 cumulative dosage are excluded.
- Prior radioisotope treatment consisting of strontium-89 or samarium-153.
- Zoledronic acid treatment for more than 3 months duration prior to registration. Other bisphosphonate treatments are permitted.
- Corrected serum calcium level less than 8 mg/dL.
- Patients may not be receiving any other investigational agents.
- 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.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to zoledronic acid or other agents used in the study
- 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.
- Symptomatic bulky lymphadenopathy causing scrotal or pedal edema or significant local invasive disease in bladder invasion.
- History of other malignancies other than nonmelanoma skin cancer, unless in complete remission and off therapy for that disease for at least 5 years.
- 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.
- 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.
- Evidence or suspicion of myelodysplastic syndrome by complete blood test (CBC) must be confirmed by bone marrow biopsy.
- Untreated symptomatic spinal cord compressions.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (4)
M.D. Anderson Cancer Center at Orlando
Orlando, Florida, 32806-2134, United States
CCOP - Wichita
Wichita, Kansas, 67214-3882, United States
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009, United States
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, 54449, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Shi-Ming Tu, MD
- Organization
- University of Texas (UT) MD Anderson Cancer Center
Study Officials
- STUDY CHAIR
Shi-Ming Tu, MD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 7, 2004
First Posted
April 8, 2004
Study Start
July 1, 2004
Primary Completion
September 1, 2014
Study Completion
September 1, 2014
Last Updated
November 10, 2016
Results First Posted
November 10, 2016
Record last verified: 2016-09