A phase II randomised controlled trial to establish if LEE0011 (ribociclib) is effective in inhibiting the growth of prostate cancer cells.

Phase 2

Completed

• Conditions: Cancer - Prostate; Prostate Cancer

• Registration Number: ACTRN12618000354280
• Lead Sponsor: niversity of Sydney

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-03-08
• Study Completion: 2023-06-20
• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Male
• Target Recruitment: 35

Inclusion Criteria

1. People with localised prostate cancer and at least clinical stage T3a Or Gleason score of between 8 and 10 Or Preoperative PSA greater than or equal to 20 ng/ml AND planned for radical prostatectomy
2. Age 18 yrs or older
3. ECOG performance 0-1
4. Histological confirmation of prostate cancer via a pre-treatment diagnostic transrectal ultrasound (TRUS) biopsy.
5. Adequate bone marrow function with platelets greater than or equal to 100 x 109/L, neutrophils greater than or equal to 1.5 x 109/L and haemoglobin greater than or equal to 90 g/L;
6. Adequate hepatic function with serum total bilirubin less than or equal to 1.5 x upper limit of normal range and ALT/SGPT and SGOT/AST less than or equal to 2.5x upper limit of normal range, serum albumin > 25 g/L, alkaline phosphatase less than or equal to 5x upper limit of normal range, and INR less than or equal to 1.5
7. Adequate renal function (with calculated creatinine clearance >50 ml/min based on the Cockcroft-Gault method, 24hour urine or GFR scan) and serum creatinine less than or equal to 1.5 x Upper Limit of Normal range (ULN);
8. Serum calcium, potassium, phosphate and magnesium within normal range or corrected with supplements
9. Study treatment both planned and able to start within 7 days of enrolment.
10. Willing and able to comply with all study requirements, including treatment and biospecimen collection
11. Signed, written informed consent (main study and biospecimen banking)

Exclusion Criteria

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the effect of LEE011 on tumour cell proliferation (frequency of a 50% reduction in the Ki-67 proliferation index from the pre-treatment prostate biopsy compared to that present in prostate cancer tissue from radical prostatectomy)[ Post treatment]