Randomised phase 3 trial of enzalutamide in androgen deprivation therapy with radiation therapy for high risk, clinically localised, prostate cancer: ENZARAD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cancer Trials Ireland

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Mar 2015 → 3 Oct 2025

Decision date (initial)

2024-09-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514808-13-00

EudraCT number

2014-003191-23

ClinicalTrials.gov

NCT02446444

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To determine effects on Metastasis-free survival (metastasis or death from any cause, MFS)

Secondary objectives 10

1. To determine effects on Overall survival (death from any cause, OS)
2. To determine effects on Prostate cancer specific survival (death from prostate cancer)
3. To determine effects on PSA progression-free survival (Phoenix criteria, or death from any cause, PSA-PFS)
4. To determine effects on Clinical progression-free survival (imaging, symptoms, signs, initiation of other anti-cancer treatment, or death from any cause, clinical-PFS)
5. To determine effects on Time to subsequent hormonal therapy (restarting ADT)
6. To determine effects on Time to castration-resistant disease (PCWG2 criteria)
7. To determine effects on Safety (adverse events - CTCAE v4.03)
8. To determine effects on Health related quality of life (EORTC QLQC-30 & PR-25, EQ-5D-FL)
9. To determine effects on Health outcomes relative to costs (incremental cost effectiveness ratio)
10. To identify biomarkers that are prognositic and/or predictive of response to treatment, safety and resistance to study treatment (associations of biomarkers with clinical outcomes)

Conditions and MedDRA coding

Localised prostate cancer at high risk of recurrence

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Pathological diagnosis of adenocarcinoma of the prostate, judged to be at high risk for recurrence based on any of the following (in accordance with the ISUP Consensus 2005 (16) see Appendix 3): Gleason score 8-10 OR Gleason score of 4+3 AND clinical T2b-4 AND PSA >20ng/mL OR N1 disease (involvement of lymph nodes at or below the bifurcation of the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or biopsy proven.
2. Age ≥ 18 yrs
3. Adequate bone marrow function: Hb ≥100g/L and WCC ≥ 4.0 x 109/L and platelets ≥100 x 109/L
4. Adequate liver function: ALT < 2 x ULN and bilirubin < 1.5 x ULN, (or if bilirubin is between 1.5 - 2 x ULN, they must have a normal conjugated bilirubin).
5. Adequate renal function: calculated creatinine clearance > 30 mL/min (Cockroft-Gault)
6. ECOG performance status of 0-1
7. Study treatment both planned and able to start within 7 days of randomisation.
8. Willing and able to comply with all study requirements, including treatment, and attending required assessments
9. Has completed the baseline HRQL questionnaires UNLESS is unable to complete because of literacy or limited vision
10. Signed, written, informed consent

Exclusion criteria 16

1. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
2. Involvement of lymph nodes superior to the common iliac bifurcation, and/or outside the pelvis (distant lymph nodes). Lymph node involvement is defined by histopathological confirmation, or by a short axis measurement >10mm on standard imaging (CT or MRI, but not PET).
3. Any contraindication to external beam radiotherapy
4. History of a. seizure or any condition that may predispose to seizure (e.g. prior cortical stroke or significant brain trauma). b. loss of consciousness or transient ischemic attack within 12 months of randomization. c. significant cardiovascular disease within the last 3 months:including myocardial infarction, unstable angina, congestive heart failure (NYHA grade II or greater, see Appendix 4), ongoing arrhythmias of Grade > 2 (NCI CTCAE, version 4.03) , thromboembolic events (e.g. deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
5. Evidence of metastatic disease: minimum imaging required is a CT and/or MRI of the abdomen and pelvis, and a whole body bone scan (WBBS). If equivocal bone scan, follow-up plain films are required to show NO evidence of cancer if not covered by CT/MRI
6. PSA > 100 ng/mL
7. History of another malignancy within 5 years prior to randomisation except for non-melanomatous carcinoma of the skin; or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours).
8. Concurrent illness, including severe infection that might jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety a. HIV-infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant enzalutamide.
9. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;
10. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception.
11. Use of hormonal therapy or androgen deprivation therapy, including enzalutamide, except in the following setting: a. Use of LHRHA (with or without anti-androgens) for less than 30 days prior to randomisation in the trial.
12. Bilateral orchidectomy or radical prostatectomy
13. Prior brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields
14. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.
15. Major surgery within 21 days prior to randomisation
16. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of enzalutamide, including difficulty swallowing tablets

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Metastasis-free survival (metastasis or death from any cause, MFS)

Secondary endpoints 9

1. Overall survival (death from any cause, OS)
2. Prostate cancer specific survival (death from prostate cancer)
3. PSA progression-free survival (Phoenix criteria, or death from any cause, PSA-PFS)
4. Clinical progression-free survival (imaging, symptoms, signs, initiation of other anti-cancer treatment, or death from any cause, clinical-PFS)
5. Time to subsequent hormonal therapy (restarting ADT)
6. Time to castration-resistant disease (PCWG2 criteria)
7. Safety (adverse events - CTCAE v4.03)
8. Health related quality of life (EORTC QLQC-30 & PR-25, EQ-5D-5L)
9. Health outcomes relative to costs (incremental cost effectiveness ration)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cancer Trials Ireland

Sponsor organisation

Cancer Trials Ireland

Address

Rcsi House, 121 Saint Stephen's Green 121 Saint Stephen's Green

City

Dublin 2

Postcode

D02 H903

Country

Ireland

Scientific contact point

Organisation

Cancer Trials Ireland

Contact name

Head of Clinical Operations

Public contact point

Organisation

Cancer Trials Ireland

Contact name

Head of Clinical Operations

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications