This clinical trial is being conducted to recommend a safe and tolerable phase 2 dose of docetaxel or cabazitaxel when combined with clarithromycin in men who have developed castrate-resistant prostate cancer. In the castrate-resistant setting, resistance to taxane therapy inevitably develops. Men who develop resistance to taxanes have a very poor prognosis, and few treatment options. It is believed that CYP enzymes contribute to docetaxel and cabazitaxel resistance in metastatic prostate cancer, and this resistance can be mitigated through pharmacologic CYP inhibition. In this study a potent CYP3A inhibitor, clarithromycin, will be co-administered concurrently with either docetaxel or cabazitaxel, whose systemic metabolism is dependent of CYP3A4, with the intent to overcome resistance to taxanes.
This is a dose-escalation study designed to determine the maximum tolerated dose of docetaxel or cabazitaxel when given in combination with clarithromycin. Eligible patients will be assigned to docetaxel or cabazitaxel, based on which drug they were previously administered prior to study entry. Enrollment to dose levels will be in a 3+3 cohort design until the maximum tolerated dose is achieved. Docetaxel or cabazitaxel will be administered on day 1 of each (3 week) cycle for a total of 6 cycles. Subjects in both arms will be administered clarithromycin on days -1, 1 and 2 of each 3 week cycle.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
4
6 infusions of Docetaxel with 18 doses clarithromycin
6 infusions of Cabazitaxel with 18 doses clarithromycin
18 doses of clarithromycin with either Docetaxel or Cabazitaxel
Johns Hopkins Hospital
Baltimore, Maryland, United States
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 3 years
Escalate dose up the maximum tolerated dose achieved, and initiate this as the recommended phase 2 dose of docetaxel and of cabazitaxel when it is combined with clarithromycin.
Time frame: 3 years
Compare docetaxel OR cabazitaxel exposure (maximal [Cmax] when combined with the strong CYP3A4 inhibitor clarithromycin to historic controls.
Time frame: 3 years
Compare docetaxel OR cabazitaxel exposure ( total [AUC]) when combined with the strong CYP3A4 inhibitor clarithromycin to historic controls.
Time frame: 3 years
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