| | Requirement |
| 1 | Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features |
| 2 | Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy (i.e., surgical or medical castration) |
| 3 | Patients who have not had a bilateral orchiectomy must have a plan to maintain effective GnRH-analogue therapy for the duration of the trial |
| 4 | Serum testosterone level < / = 1.73 nmol/l (50 ng/dl) at the screening visit |
| 5 | Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks |
| 6 | Progressive disease at study entry - defined as one or more of the following three criteria that occurred while the patient was on androgen deprivation therapy: [a] PSA progression defined by a minimum of two rising PSA levels with an interval of = / > 1 week between each determination. Patients who received an anti-androgen must have progression after withdrawal (= / > 4 weeks since last flutamide or = / > 6 weeks since last bicalutamide or nilutamide). The PSA value at the screening visit should be = / > 2 µg/l (2 ng/ml); [b] Soft tissue disease progression defined by RECIST 1.1; [c] Bone disease progression defined by PCWG2 with two or more new lesions on bone scan |
| 7 | Metastatic disease documented by bone lesions on bone scan or by measurable soft tissue disease by CT/MRI. Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible |
| 8 | Asymptomatic or mildly symptomatic from prostate cancer |
| 9 | ECOG performance status 0–1 |
| 10 | Estimated life expectancy of = / > 6 months |
| 11 | AGC = / > 1.5; platelets = / > 100,000; Hgb = / > 9.0 (NOTE: Patients may not have received any growth factors within 7 days or blood transfusions within 28 days of the hematologic lab values obtained at the screening visit) |
| 12 | Total bilirubin, SGOT or SGPT < / = 2.5 x uln at screening; albumin = / > 3.0 at screening |
| 13 | Creatinine < / = 2.0 at screening |
| 14 | Able to swallow the study drug and comply with study requirements |
| 15 | Signed an approved study-specific informed consent and HIPAA |
| 1 | Prior cytotoxic chemotherapy for prostate cancer |
| 2 | Severe concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment |
| 3 | Known or suspected brain metastasis or active leptomeningeal disease |
| 4 | History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer |
| 5 | History of seizure or any condition that may predispose to seizure. Also, history of loss of consciousness or TIA within 12 months of enrollment |
| 6 | Clinically significant cardiovascular disease including: [a] MI within 6 months; [b] uncontrolled angina within 3 months; [c] CHF NYHA class 3 or 4, or patients with history of CHF NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within 3 months results in a LVEF = / > 45%; [d] History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes); [e] History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place; [f] Hypotension as indicated by systolic BP < 86 mmHg at the screening visit; [g] Bradycardia as indicated by a heart rate of <50 beats/min on the screening ECG; [h] Uncontrolled HTN as indicated by systolic BP >170 mmHg or diastolic BP >105 mmHg at the screening visit. |
| 7 | GI disorder affecting absorption (e.g., gastrectomy, active PUD within last 3 months |
| 8 | Major surgery within 4 weeks of enrollment |
| 9 | Use of opiate analgesics for pain from prostate cancer within 4 weeks of enrollment |
| 10 | RT for treatment of the primary tumor within 3 weeks of enrollment |
| 11 | RT or radionuclide therapy for treatment of metastasis |
| 12 | Treatment with flutamide within 4 weeks of enrollment |
| 13 | Treatment with bicalutamide or nilutamide within 6 weeks of enrollment |
| 14 | Treatment with 5-alpha reductase inhibitors (finasteride, dutasteride), estrogens, cytproterone within 4 weeks of enrollment |
| 15 | Treatment with systemic biologic therapy for prostate cancer (other than approved bone targeted agents and GnRH-analogue therapy) or other agents with anti-tumor activity within 4 weeks of enrollment |
| 16 | History of prostate cancer progression on ketoconazole |
| 17 | Prior use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683, TAK-448) or blocks the androgen receptor (e.g., BMS 641988) |
| 18 | Participation in a previous clinical trial of MDV3100 |
| 19 | Use of an investigational agent within 4 weeks of enrollment |
| 20 | Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of enrollment |
| 21 | Any condition or reason that, in the opinion of the investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data |
