Fractionated Docetaxel and Radium 223 in Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the prostate
• Documented metastatic castration resistant disease with PSA progression, radiographic progression, or both, despite medical or surgical castration
• Two or more bone metastases detected on skeletal scintigraphy
• Eligible for docetaxel chemotherapy
• ECOG Performance Status 0-2
• Adequate organ function:
• Hemoglobin > 10 g/dL
• Absolute Neutrophil Count ≥ 1,500 K/mL
• Platelet count ≥ 150,000 x 10^9/L
• Total bilirubin ≤ 1.5x upper limit of normal range, excluding Gilbert syndrome
• Serum AST ≤ 1.5 x upper limit of normal range
• Serum ALT ≤ 1.5 x upper limit of normal range
• Estimated glomerular filtration rate (GFR) > 30mL/min
• Ongoing castration (androgen deprivation therapy or prior orchiectomy)
• Male subjects with female sexual partners of childbearing potential must agree to use at least one highly effective methods of birth control.
• Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures.
• Age ≥ 18 years

Exclusion Criteria

• Prior radionuclide therapy for CRPC
• Prior docetaxel for CRPC. (Permitted if given for castration sensitive disease > 6 months prior).
• Antiandrogen therapy within 4 weeks of enrollment. However, patients with primary failure of secondary anti-androgen therapy OR symptomatic progression, objective progression and/or biochemical evidence of rising PSA less than 4 weeks after discontinuation of anti-androgen therapy will not have anti-androgen withdrawal responses and will not be excluded.
• Preexisting peripheral neuropathy grade 2 or higher.
• Other serious medical condition as judged by the investigator.
• Active second malignancy that requires therapy.
• Known brain or leptomeningeal metastases
• Concurrent enrollment in any other investigational anticancer therapy
• Treatment with any myelosuppressive agent within 30 days of enrollment
• Presence of bulky visceral metastases, defined as any of the following:
• ≥ 4 lung lesions (at least 1cm each in size in the longest diameter) or pulmonary lymphangitic metastasis
• Liver metastases with sum of lesion diameters totaling ≥ 5cm
• Evidence of neuroendocrine or small cell differentiation on prior biopsy
• History of severe hypersensitivity reactions to docetaxel or to drugs formulated with polysorbate 80