A Randomized Phase II Study Of Bone-Targeted Therapy In Advanced Androgen-Dependent Prostate Cancer
Doxorubicin hydrochloride
+ Goserelin acetate
+ Leuprolide acetate
Urogenital Diseases+7
+ Genital Diseases
+ Genital Diseases, Male
Treatment Study
Summary
Study start date: July 1, 2004
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.80 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Male
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.2 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 4 locations
CCOP - Wichita
Wichita, United StatesM.D. Anderson Cancer Center at University of Texas
Houston, United StatesCCOP - Marshfield Clinic Research Foundation
Marshfield, United States