Therapeutics in Active Prostate Cancer Surveillance (TAPS02)

Sponsor

Cambridge University Hospitals NHS Foundation Trust (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05191680

Collaborator

University of Cambridge (Other), Janssen-Cilag Ltd. (Industry)

335

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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

Anticipated 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).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)

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2030

Anticipated Study Completion Date :

Jul 1, 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 Names: 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 Names: 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

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 Names:

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 Names:

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

MRI defined tumour volume (Pilot phase) [12 months after end of treatment]
>50% reduction in tumour volume
Cumulative rate of disease progression (Full Trial) [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

Reported adverse events (Pilot phase) [12 months after end of treatment]
as per NCI-CTCAE v5.0
Patient-reported outcomes (Pilot phase) [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).
Reported adverse events (Full Trial) [3 years after completion of treatment]
as per NCI-CTCAE v5.0
Patient-reported outcomes (Full Trial) [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).
Cumulative rate of progression to radical treatment (Full Trial) [3 years after completion of treatment]
Patient-reported outcomes (Pilot phase) [cumulative until 12 months after end of treatment]
Assessed using the EQ-5D-5L questionnaire developed by the EuroQol Group.
Patient-reported outcomes (Full Trial) [cumulative until 3 years after completion of treatment]
Assessed using the EQ-5D-5L questionnaire developed by the EuroQol Group.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Locations

No locations specified.

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

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

First Posted:

Jan 13, 2022

Last Update Posted:

Jan 13, 2022

Last Verified:

Jan 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Vincent Gnanapragasam, Professor of Urology and Honorary Consultant Urologist, 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

Study Results

No Results Posted as of Jan 13, 2022