LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in mCRPC

Inclusion Criteria

• Histologically confirmed prostate cancer. Small cell/neuroendocrine differentiated allowed but not required for study participation.
• Progressive metastatic prostate cancer (as defined below in Item #5) despite castrate levels of testosterone ( 450 msec
• Bradycardia (heart rate 100 bpm at rest)
• P-R interval > 220msec,
• QRS interval >109 msec
• Documented cardiomyopathy
• Systolic blood pressure >160 mmHg or 1.5 x ULN with concomitant alkaline phosphatase > 2.5 x ULN
• Patient receiving any of the following medications within 7 days of day 1 of study treatment.
• Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
• That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
• That have a known risk to prolong the QT interval or induce Torsades de Pointes.
• Herbal preparations/medications
• Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study drug at a dose greater than the equivalent of 10 mg prednisone/day, or who have not fully recovered from the side effects of such treatment
• The following uses of corticosteroids are permitted: short duration (<5 days) of systemic corticosteroids; any duration of topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular).
• Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, direct thrombin inhibitors, low molecular weight heparin (LMWH) or fondaparinux is allowed.
• Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer
• Major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).
• Patient who has received radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia), and/or in whom ≥25% of the bone marrow was irradiated.
• Patient has a known history of HIV infection (testing not required)
• Patient has not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAE version 4.03 to less than or equal to Grade 1 (Exception to this criterion: patients with grade 1 taxane-induced neuropathy, any grade of alopecia, amenorrhea or other toxicities not considered a safety risk for the patient as per investigator's discretion, are allowed to enter the study).
• Patients with chronic liver disease with a Child-Pugh score B or C.
• Patients with serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy.
• Patients with severe psychiatric illness/social situations that would limit compliance with study requirements in the judgment of study investigator.
• History of bleeding diathesis. Patients receiving anti-coagulation must be able safely interrupt treatment for tumor biopsy (Phase 2 only)
• Patient has a history of non-compliance to medical regimen or inability to grant consent