Cohorts of Docetaxel or Cabazitaxel in Combination With the Potent CYP3A4 Inhibitor, Clarithromycin

1. Men with metastatic castrate-resistant prostate cancer (prostate cancer progressing despite castrate levels of testosterone \<50 ng/dL), using standard measures of progression defined by PCWG2
2. Have received at least 4 cycles of docetaxel or cabazitaxel, and less than ten, with two consecutive rising PSA values, checked at least 7 days apart. No PSA decline in last 42 day
3. Bone disease documented by either: a positive bone scan, CT scan, or MRI; or biopsy-proven bony metastases
4. Age ≥18 years
5. ECOG performance status ≤ 2 (Karnofsky ≥ 60%)

6. Have normal organ and marrow function defined as:

   • absolute neutrophil count ≥1,500/mcL
   • platelets ≥100,000/mcL
   • total bilirubin (within normal institutional limits)
   • AST/ALT ≤ 2.5 × ULN (or ≤ 1.5 x ULN in conjunction with alk phos >2.5 x ULN for Docetaxel
   • AST ≤ 1.5 x ULN for Cabazitaxel
   • creatinine clearance-no minimum for Docetaxel
   • creatinine clearance- ≥ 30 mL/min/1.73 m2 for Cabazitaxel
7. No evidence of clinical progression, in the form of increased lesions on cross-sectional imaging, or new cancer-attributable symptoms or worsening of existing symptoms
8. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Patients who have residual toxicities > Grade 2 attributed to taxane therapy, except for neuropathy, who are excluded if > grade 1
2. Patients who are receiving any other investigational agents or have within the last 28 day.
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to clarithromycin or taxanes
4. Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
6. Received more than 10 cycles of docetaxel [for docetaxel cohort only] or 6 of cabazitaxel [for cabazitaxel cohort only]
7. Last docetaxel or cabazitaxel dose > 6 weeks prior to enrollment
8. Patients with a documented history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes, or taking drugs that are known to prolong the QT