LEEP: This phase II trial is trying to determine the effectiveness of a targeted cancer drug (ribociclib) at slowing down the growth of prostate cancer cellsA Randomised controlled Phase II trial of the pharmacodynamic effects of CDK4/6 inhibitor LEE011 (ribociclib) in high-risk, localised prostate cancer

Exclusion

1. Major surgery less than or equal to 2 weeks prior to enrolment or who have not recovered from side effects of such therapy. Transrectal ultrasound (TRUS) biopsy is not considered major surgery in this study.
2. Known hypersensitivity to the study drug or its excipients
3. Diarrhoea greater than or equal to CTCAE grade 2
4. Impaired cardiac function, including any one of the following:
a) History (or family history) of long QT syndrome
b) Ribociclib should be avoided in patients who already have or who are at significant risk of developing QTc prolongation. This includes patients with:
• long QT syndrome
• Mean QTcF greater than or equal to 450 msec on baseline ECG
• uncontrolled or significant cardiac disease including recent myocardial infarction,
• congestive heart failure, unstable angina and bradyarrhythmias
• electrolyte abnormalities
• clinically significant ECG abnormalities at clinical discretion

c) History of clinically manifested ischemic heart disease less than or equal to 6 months prior to study start
d) History of heart failure or left ventricular (LV) dysfunction (LVEF less than or equal to 50%)
e) Other clinically significant heart disease (e.g. uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
f) Clinically significant resting bradycardia (< 50 beats per minute)
g) Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be discontinued or switched to an alternative drug prior to commencing start of treatment.
h) Obligate use of a cardiac pacemaker
5. Patients who have received prior antineoplastic therapy for advanced disease.
6. Prior treatment with an CDK4/6 inhibitor
7. Patients who are currently receiving treatment with strong CYP3A4 inhibitors and cannot be discontinued or switched to an alternative drug prior to commencing start of treatment.
8. Patients receiving chronic or high dose corticosteroids therapy (Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed)
9. Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. Testing for these is not mandatory unless clinically indicated.
10. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.