Therapeutics in Active Prostate Cancer Surveillance (TAPS02)

• ClinicalTrials.gov Identifier: NCT05191680
• Recruitment Status: Not yet recruiting
• First Posted: January 13, 2022
• Last Update Posted: January 13, 2022
• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: University of Cambridge; Janssen-Cilag Ltd.
• Information provided by (Responsible Party): Vincent Gnanapragasam, Cambridge University Hospitals NHS Foundation Trust

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Apalutamide Oral Tablet [Erleada]; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 335 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The trial will occur in 2 phases. Following an initial 3-arm pilot phase, a go-no go decision will be made. If successful, the trial will progress and adapt to become a 2-arm trial in the subsequent phase (one treatment arm from the pilot phase will be dropped).
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Targeted Drug Intervention to Inhibit Cancer Progression in Men on Active Surveillance for Favourable Prognosis Prostate Cancer: A Randomised Trial - Therapeutics in Active Prostate Cancer Surveillance (TAPS02)
• Estimated Study Start Date: July 2022
• Estimated Primary Completion Date: July 2030
• Estimated Study Completion Date: July 2030

Arms and Interventions

Arm	Intervention/treatment
Experimental: Apalutamide 6 months; Participants will receive apalutamide 240 mg (4 x 60 mg tablets) orally once a day for up to 6 months.	Drug: Apalutamide Oral Tablet [Erleada]; Apalutamide is a selective Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR.; Other Name: Erleada
Experimental: Apalutamide 3 months + Placebo 3 months; Participants will receive apalutamide 240mg (4 x 60 mg tablets) orally once a day for up to 3 months followed by placebo to match apalutamide (4 tablets) orally once a day for up to 3 months.	Drug: Apalutamide Oral Tablet [Erleada]; Apalutamide is a selective Androgen Receptor (AR) inhibitor that binds directly to the ligand-binding domain of the AR.; Other Name: Erleada
Placebo Comparator: Placebo 6 months; Participants will receive placebo to match apalutamide (4 tablets) orally once a day for up to 6 months.	Drug: Placebo; Placebo to match apalutamide

Outcome Measures

Primary Outcome Measures :

1. MRI defined tumour volume (Pilot phase) [ Time Frame: 12 months after end of treatment ]
   >50% reduction in tumour volume
2. Cumulative rate of disease progression (Full Trial) [ Time Frame: 3 years after completion of treatment ]
   Progression defined as tumour classification into a Grade Group 3 and/or T3 stage and/or composite score of ≥CPG3 disease (The Cambridge Prognostic Group classification system, CPG1-CPG5)

Secondary Outcome Measures :

1. Reported adverse events (Pilot phase) [ Time Frame: 12 months after end of treatment ]
   as per NCI-CTCAE v5.0
2. Patient-reported outcomes (Pilot phase) [ Time Frame: cumulative until 12 months after end of treatment ]
   Assessed using the European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients questionnaire (EORTC-QLQC30).
3. Reported adverse events (Full Trial) [ Time Frame: 3 years after completion of treatment ]
   as per NCI-CTCAE v5.0
4. Patient-reported outcomes (Full Trial) [ Time Frame: cumulative until 3 years after completion of treatment ]
   Assessed using the European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients questionnaire (EORTC-QLQC30).
5. Cumulative rate of progression to radical treatment (Full Trial) [ Time Frame: 3 years after completion of treatment ]
6. Patient-reported outcomes (Pilot phase) [ Time Frame: cumulative until 12 months after end of treatment ]
   Assessed using the EQ-5D-5L questionnaire developed by the EuroQol Group.
7. Patient-reported outcomes (Full Trial) [ Time Frame: cumulative until 3 years after completion of treatment ]
   Assessed using the EQ-5D-5L questionnaire developed by the EuroQol Group.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Aneta Drozd; 01223256364; aneta.drozd@addenbrookes.nhs.uk

Sponsors and Collaborators

Cambridge University Hospitals NHS Foundation Trust

University of Cambridge

Janssen-Cilag Ltd.

Investigators

• Principal Investigator: Vincent J Gnanapragasam, Prof.; Cambridge University Hospitals NHS Foundation Trust

More Information

• Responsible Party: Vincent Gnanapragasam, Professor of Urology and Honorary Consultant Urologist, Cambridge University Hospitals NHS Foundation Trust
• ClinicalTrials.gov Identifier: NCT05191680
• Other Study ID Numbers: TAPS02; 2021-006106-75 ( EudraCT Number )
• First Posted: January 13, 2022
• Last Update Posted: January 13, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Vincent Gnanapragasam, Cambridge University Hospitals NHS Foundation Trust:

active surveillance; prostate cancer; therapeutics in prostate cancer; apalutamide; short term androgen deprivation therapy; androgen receptor inhibitor

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases