Therapeutics in Active Prostate Cancer Surveillance (TAPS02)

• Status: Not yet recruiting
• Trial end date: 2030-07-01
• Target enrollment: 0
• Participant gender: Male

Summary

This is a phase 3, randomised, multicentre, double-blind, placebo-controlled trial investigating the use of short term androgen deprivation therapy in the form of apalutamide (Erleada) in men on active surveillance for prostate cancer.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: Janssen-Cilag Ltd.; University of Cambridge

Criteria

Inclusion Criteria:

• signed informed consent.

• have an Eastern Cooperative Oncology Group (ECOG) status 0-2.

• have selected active surveillance as a management option.

• have an mpMRI (multi parametric Magnetic Resonance Imaging) detectable lesion with an M score of ≥ 3 using Likert scale OR PIRADS (Prostate Imaging Reporting and Data System (PIRADS) version 2.1) reporting criteria.

• have prostate cancer from a combination of image guided targeted + systematic biopsies and MRI lesion and biopsy are concordant for a prostate cancer diagnosis.

• not anticipated to require bladder outlet surgery during drug treatment or up to 12 months of Follow Up.

Meet all of the following clinical laboratory assessment criteria:

• haemoglobin ≥ 9.0 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomisation.

• platelet count ≥ 100 x 10^9/L independent of transfusion and/or growth factors within 3 months prior to randomisation.

• absolute neutrophil count (ANC) ≥ 1350/µL.

• serum albumin ≥ 3.0 g/dL.

• glomerular filtration rate (GFR) ≥ 30ml/min AND Serum creatinine ≤ 2 times the ULN concurrent with creatinine clearance ≥ 50mL/min (calculated by Cockcroft and Gault equation).

• serum potassium ≥3.5 mmol/L.

• aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <2.5 × ULN AND Serum total bilirubin ≤1.5 × ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible).

• have prostate cancer with any one or more of the following:

• Cambridge Prognostic Group 2 (Favourable intermediate risk prostate cancer by AUA criteria) OR CPG1 (AUA Low risk) with PSA high density (PSAd>0.15).

• have a LIKERT or PIRADS 4/5 lesion (individual or combined) of ≥10mm and be at least CPG1 (no PSAd limit).

Exclusion Criteria:

• Contraindications to apalutamide or its excipients.

• Pelvic metalwork interfering with MRI prostate interpretation.

• Any prior use of androgen deprivation therapy or androgen receptor targeting agents (not including 5-alpha reductase inhibitors).

• Any prior systemic therapy for prostate cancer.

• Inability for patient to have prostate mpMRI scan.

• Concurrent CTIMP involvement; participation in an observational study/ studies is acceptable.

• Seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to randomisation, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing oedema or mass effect).

• Participant has history/is at risk of falls/fracture.

• Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomisation. Cardiovascular risk factors should be optimised i.e. hypertension, diabetes, dyslipidaemia.

• Uncontrolled hypertension (SBP ≥ 160 mmHg or DBP≥90 mmHg). Patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment.

• Gastrointestinal disorder affecting absorption.

• Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry.

• Medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes.

• Strong inhibitors of CYP2C8.

• Strong inhibitors of CYP3A4.