Clinical trial NCT00415779: ZANTE: Zometa and Taxotere in Hormone Refractory Prostate Cancer
Official title: Phase I Study of the Combination of Zoledronic Acid and Docetaxel in Patients With Hormone Refractory Metastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Prostate Cancer
Keywords: hormone refractory
bone metastasis
chemotherapy
biphosphonates
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2006-12-25
Enrollment: 36
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: to determine the maximum tolerated dose and dose limiting toxicity of docetaxel in the two treatment schedules
timeFrame: every 2 weeks for up to 3 cycles
Secondary outcomes:
measure: to determine the recommended docetaxel dose when combined with zoledronic acid for phase II studies
timeFrame: every 2 weeks for 6 cycles
measure: to determine which administration sequence of the combination permits a higher dosage of docetaxel
timeFrame: every 2 weeks for 6 weeks
measure: to describe the toxicity of the combination of the two drugs
timeFrame: every 2 weeks
measure: to describe the effects of the combination of the two drugs on biologic parameters: angiogenetic factors, cytokines, differential neuroendocrine markers, serum markers of osteolysis
timeFrame: every 12 weeks
measure: to describe the antitumor activity of the two drug association
timeFrame: every 12 weeks
Other outcomes:
Locations:
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori
city: Rionero in Vulture
country: Italy
facility: Ospedale Oncologico Regionale C.R.O.B. - Basilicata
Study officials:
affiliation: Experimental Pharmacology, National Cancer Institute Naples
name: Michele Caraglia, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Experimental Pharmacology, National Cancer Institute Naples
name: Alfredo Budillon, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Cancer Institute Naples, Italy; Director Clinical Trials Unit
name: Francesco Perrone, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Oncology B, National Cancer Institute Naples
name: R. Vincenzo Iaffaioli, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Oncology B, National Cancer Institute Naples
name: Gaetano Facchini, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Trials Unit, National Cancer Institute Naples
name: Alessandro Morabito, M.D.
role: PRINCIPAL_INVESTIGATOR
References: