Phase I Study of the Combination of Zoledronic Acid and Docetaxel in Patients With Hormone Refractory Metastatic Prostate Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 36
- Locations
- 3
- Primary Endpoint
- to determine the maximum tolerated dose and dose limiting toxicity of docetaxel in the two treatment schedules
Study Overview
Brief Summary
This phase I trial is studying the side effects and best dose of docetaxel when given with zoledronic acid in patients with bone metastasis from prostate cancer that has not responded to hormone therapy.
Detailed Description
Docetaxel has been used alone and in combination with other anti-cancer therapies in the treatment of hormone refractory metastatic prostate cancer. Zoledronic acid has been used in the treatment of bone metastasis from prostate cancer. This is a study of the combination of these two agents. The Zante study will test a dose escalation of docetaxel in association with a predetermined dose of zoledronic acid (2 mg), given every 14 days for a minimum of 6 and maximum of 12 cycles.
Sequence A: Docetaxel on day 1 and zoledronic acid on day 2
Sequence B: Zoledronic acid on day 1 and docetaxel on day 2
Patients are enrolled sequentially in cohorts of 3 for each dose level, and a maximum of 36 patients will be enrolled.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent
- •Hormone refractory prostate cancer
- •Stage IV disease with bone metastasis
- •No immunotherapy, hormonal therapy or radiotherapy within the previous month
- •Performance status < or = 2 (ECOG)
- •Serum creatinine < 1.5 mg/100ml
- •Serum bilirubin < or = 1.25 x UNL (upper normal limit) (or < or = 1.5 x UNL in the presence of hepatic metastases); SGOT e SGPT < or = 1.5 x UNL (or < or = 2.5 x UNL in presence of hepatic metastases)
- •Left ventricular ejection fraction > or = 50% (measured by cardiac ultrasound or MUGA scan)
- •Neutrophils > 1500/mm3; platelets >100000/mm3; hemoglobin >10 g/100 ml· Life expectancy of at least 3 months
Exclusion Criteria
- •Previous malignancies with the exception of radically treated epithelioma
- •Previous chemotherapy
- •Comorbidities that would, in the Investigator's opinion, contraindicate the use of the drugs in the study
- •Uncontrolled Diabetes
- •Severe cardiac arrhythmias, severe uncontrolled congestive heart failure, severe ischemic cardiac disease or myocardial infarction within the previous 6 months
- •severe infection
- •cerebral metastasis
- •Pre-existing motor or sensory neurotoxicity > or = grade 2 according to CTC (Common Toxicity Criteria).
Outcomes
Primary Outcomes
to determine the maximum tolerated dose and dose limiting toxicity of docetaxel in the two treatment schedules
Time Frame: every 2 weeks for up to 3 cycles
Secondary Outcomes
- to determine the recommended docetaxel dose when combined with zoledronic acid for phase II studies(every 2 weeks for 6 cycles)
- to determine which administration sequence of the combination permits a higher dosage of docetaxel(every 2 weeks for 6 weeks)
- to describe the toxicity of the combination of the two drugs(every 2 weeks)
- to describe the effects of the combination of the two drugs on biologic parameters: angiogenetic factors, cytokines, differential neuroendocrine markers, serum markers of osteolysis(every 12 weeks)
- to describe the antitumor activity of the two drug association(every 12 weeks)