E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prostate cancer, managed by active surveillance - low or intermediate risk according to NICE classification and an MRI score of ≥ 3 for lesion probability using PIRAD version 2 reporting criteria. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with prostate cancer being managed through active surveillance. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to test if short-term use of apalutamide can reduce image defined tumour volumes in men with prostate cancer and a detectable lesion on multi-parametric MRI (mpMRI) who are being managed by Active Surveillance (AS). |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to evaluate the tolerability and side effect profile of men on AS using short-term apalutamide as a therapeutic strategy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Given Informed Consent (IC) to participate - Age 18 or over - ECOG status 0-2 - Diagnosed with prostate cancer - Patient selection of active surveillance as a management option - mpMRI detectable lesion - Prostate cancer on biopsy from a mpMRI defined lesion - Willing to use two high effective forms of contraception throughout their participation in the trial and for three months after their last dose - Normal full blood count and normal renal and liver function tests - At least 6 months since initiation of active surveillance and/or last rebiopsy date. - Low of intermediate risk according to NICE classification - MRI score of ≥ 3 using PIRAD version 2 reporting criteria - Adequate haematological, renal and liver organ function (measured within 14 days prior to planned first trial drug administration) |
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E.4 | Principal exclusion criteria |
- Contraindication to apalutamide or its excipients - Concurrent medication that can lower seizure threshold - Clinically significant change in tumour volume as assessed by mpMRI at the baseline in comparison with the previous standard of care mpMRI prior to enrolment into the trial - Prior localised or systemic therapy for prostate cancer - Prior use of androgen deprivation therapy or androgen receptor targeting agents - Prior systemic therapy for prostate cancer - Patient unable to have prostate 3T mpMRI scan - Presence of any pelvic or hip metalwork - Conditions resulting in the inability to swallow or absorb the trial drug or contrast agents - Poor medical risk due to uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection, or as judged by the investigator. - Patient unsuitable to participate as unlikely to comply with trial procedures, as judged by the investigator - Patient with previous non-related malignancy that have undergone treatment with curative intent or who are ongoing treatment - Participation in any other clinical trials involving an IMP or interventional delivery |
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E.5 End points |
E.5.1 | Primary end point(s) |
Physiological response defined as achieving tumour downsizing as determined by mpMRI or absence of a lesion, 90 days from the start of treatment with the trial drug. mpMRI will include standard T2 weighted imaging, diffusion weighted imaging and dynamic contrast enhancement. The use of mpMRI as a surrogate marker of treatment response in window trials has been reported from our institute. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and on day 90 of IMP administration |
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E.5.2 | Secondary end point(s) |
Tolerability and side effects assessed using patient-reported outcomes measuring urinary and sexual function as well as overall wellbeing using established and standardised questionnaires: (i) European Organisation for research and Treatment of Cancer (EORTC)-QLQ 30 + prostate specific module (PR 25) and (ii) the EuroQol (EQ-5D-5L) questionnaire.
Adverse events (according to NCI-CTCAE v4.03)
Exploratory outcome measure: Patient acceptability measured as percentage of patients recruited from patients consented or approached; reasons for declined participation; reasons for withdrawal.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary & exploratory endpoints will be assessed at all visits during the clinical trial. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of trial will be the date of the last patient’s last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 1 |