TherApeutics in Early ProState Cancer (TAPS02)

• ClinicalTrials.gov Identifier: NCT05191680
• Recruitment Status: Recruiting
• First Posted: January 13, 2022
• Last Update Posted: April 28, 2023
• 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: 402 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The trial will occur in two stages. Following an initial 3-arm Pilot stage, 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 stage.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Targeted Drug Intervention in Men at Risk of Progression on Active Surveillance for Early Prostate Cancer: A Randomised Trial - Therapeutics in Active Prostate Cancer Surveillance (TAPS02).
• Actual Study Start Date: April 24, 2023
• Estimated Primary Completion Date: April 2031
• Estimated Study Completion Date: April 2031

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) [ Time Frame: 12 months after end of treatment ]
   To determine whether there is a reduction in MRI defined tumour volume at 12 months post treatment in at least 50% of the treated cohort in either treatment arm compared to the baseline measurement.
2. Cumulative rate of disease progression (Full Trial) [ Time Frame: 3 years after completion of treatment ]
   To determine whether there is a 50% reduction in cumulative 3-year progression rate to ≥ Grade Group 3 or T3 stage and composite score of ≥ CPG3 disease.

Secondary Outcome Measures :

1. Reported adverse events (Pilot) [ Time Frame: Reported from the point of obtaining informed consent until the safety FU visit (30-45 days post-treatment) ]
   As per NCI-CTCAE v5.0
2. Patient-reported outcomes (Pilot) [ 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. Patient-reported outcomes (Pilot) [ Time Frame: Cumulative until 12 months after end of treatment ]
   Assessed using the EQ-5D-5L questionnaire developed by the EuroQol Group.
4. Reported adverse events (Full Trial) [ Time Frame: Reported from the point of obtaining informed consent until the safety FU visit (30-45 days post-treatment) ]
   As per NCI-CTCAE v5.0
5. 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).
6. 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.
7. Cumulative rate of progression (any progression) (Full Trial) [ Time Frame: 3 years after completion of treatment ]
8. Cumulative rate of progression to radical treatment (for any cause) (Full Trial) [ Time Frame: 3 years after completion of treatment ]

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

To be included in the trial the patient must:

• Have given written informed consent to participate.
• Be aged 18 or over.
• Have an Eastern Cooperative Oncology Group (ECOG) status 0-2.
• Have selected active surveillance as a management option.
• Have an MRI detectable lesion with an M score of ≥ 3 using Likert scale OR PIRADS (version 2.1) reporting criteria. If M score is 3 then lesion size (single or combined) of ≥10mm.
• 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 IMP treatment or for 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 109/L independent of transfusion and/or growth factors within 3 months prior to randomisation.
  • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L within 21 days prior to randomisation.
  • Serum albumin ≥ 3.0 g/dL within 21 days prior to randomisation.
  • Glomerular filtration rate (GFR) ≥ 30 ml/min AND Serum creatinine ≤ 3 times the ULN (calculated by Cockcroft and Gault equation using actual body weight) within 21 days prior to randomisation.
  • Serum potassium ≥3.5 mmol/L within 21 days prior to randomisation.
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤2.5 × ULN AND Serum total bilirubin ≤1.5 × ULN within 21 days prior to randomisation (Note: In patients with confirmed Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, patient may be eligible in consultation with their physician).

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

  • CPG2 (based on Grade Group 2 on histology)
  • CPG1 (based on Grade Group 1 on histology) with PSA high density (PSAd >0.15) and LIKERT or PIRADS 4/5 lesion (individual or combined) of ≥10mm size.
  • CPG1 with PSA high density (PSAd >0.15) and ≥50% biopsy core involvement (number of positive cores/all cores taken) with target biopsies counted as one if LIKERT or PIRADS 3 lesion

EXCLUSION CRITERIA

The presence of any of the following will preclude patient inclusion:

• Contraindications to apalutamide or its excipients.
• Pelvic metalwork interfering with MRI prostate interpretation.
• Any prior or concurrent use of androgen deprivation therapy (ADT) or androgen receptor targeting agents (not including established and continued use of 5-ARIs for urinary symptoms).
• Systemic therapy for prostate cancer.
• No concurrent use of any other ADT.
• Inability for patient to have prostate MRI scan.
• Concurrent involvement in a Clinical Trial of Investigational Medicinal Product (CTIMP); participation in an observational trial/studies is acceptable.
• Seizure or known condition that may pre-dispose to seizure (including but not limited to the following within 1 year prior to randomisation: prior stroke, transient ischemic attack, loss of consciousness, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing oedema or mass effect).
• Medications known to lower the seizure threshold or cause seizures must be discontinued or substituted at least 28 days prior to randomisation.
• Patient 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.
• Medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes such as class IA (e.g., quinidine, disopyramide) or class III (e.g., amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic medicinal products, methadone, moxifloxacin, antipsychotics (e.g. haloperidol), etc. should be carefully evaluated.
• Symptoms suggestive of Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).

Contacts and Locations

Contacts

Contact: Aneta Drozd; 01223256364; cuh.taps02trial@nhs.net

Locations

United Kingdom

Addenbrooke's Hospital; Recruiting

Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ

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: April 28, 2023
• Last Verified: April 2023

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; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases