Randomised phase 3 trial of enzalutamide in first line androgen deprivation therapy for metastatic prostate cancer: ENZAMET

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

18 Dec 2014 → ongoing

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516137-13-00

EudraCT number

2014-003190-42

ClinicalTrials.gov

NCT02446405

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To determine effects on overall survival (death from any cause)

Secondary objectives 6

1. To determine effects on Prostate specific antigen progression free survival (PCGW2)
2. To determine effects on Clinical progression free survival (imaging, symptoms, signs)
3. To determine effects on Adverse events (CTCAE v4.03)
4. To determine effects on Health related quality of life (EORTC QLQ C-30, PR-25 and EQ-5D-5L)
5. To determine effects on Health outcomes relative to costs (incremental cost effectiveness ratio)
6. To identify biomarkers that are prognostic and/or predictive of response to treatment, safety and resistance to study treatment (associations of biomarkers with clinical outcomes)

Conditions and MedDRA coding

Metastatic Prostate Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male aged 18 or older with metastatic adenocarcinoma of the prostate defined by Documented histopathology or cytopathology of prostate adenocarcinoma from a biopsy of a metastatic site OR Documented histopathology of prostate adenocarcinoma from a TRUS biopsy, radical prostatectomy, or TURP and metastatic disease consistent with prostate cancer. OR Metastatic disease typical of prostate cancer (i.e. involving bone or pelvic lymph nodes or para-aortic lymph nodes) AND a serum concentration of PSA that is rising and >20ng/mL
2. Target or non-target lesions according to RECIST 1.1
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 1.5-2x ULN, they must have a normal conjugated bilirubin). If liver metastases are present ALT must be < 5xULN
5. Adequate renal function: calculated creatinine clearance > 30 ml/min (Cockroft-Gault)
6. ECOG performance status of 0-2. Patients with performance status 2 are only eligible if the decline in performance status is due to metastatic prostate cancer.
7. Study treatment both planned and able to start within 7 days after randomisation.
8. Willing and able to comply with all study requirements, including treatment and required assessments
9. Has completed baseline HRQL questionnaires UNLESS is unable to complete because of limited literacy or vision
10. Signed, written, informed consent

Exclusion criteria 10

1. Prior cytotoxic chemotherapy for prostate cancer, but up to 2 cycles of docetaxel chemotherapy for metastatic disease is permitted.as per section 5.3.2.4 is allowed.
2. Participation in other clinical trials of investigational agents for the treatment of prostate cancer or other diseases.
3. Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components
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 functional capacity class II or greater, Refer to Appendix 6), ongoing arrhythmias of Grade >2 [CTCAE, version 4.03], thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism). Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
5. Life expectancy of less than 12 months.
6. History of another malignancy within 5 years prior to randomisation, except for either non- melanomatous carcinoma of the skin or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta and low grade T1 tumours).
7. 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.
8. 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
9. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception.
10. Prior ADT for prostate cancer (including bilateral orchidectomy), except in the following settings: a. Started less than 12 weeks prior to randomisation AND PSA is stable or falling. The 12 weeks starts from whichever of the following occurs earliest: first dose of oral anti- androgen, LHRHA, or surgical castration. b. In the adjuvant setting, where the completion of adjuvant hormonal therapy was more than 12 months prior to randomisation AND the total duration of hormonal treatment did not exceed 24 months. For depot preparations, hormonal therapy is deemed to have started with the first dose and to have been completed when the next dose would otherwise have been due, e.g. 12 weeks after the last dose of depot goserelin 10.8mg.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (death from any cause)

Secondary endpoints 5

1. Prostate specific antigen progression free survival (PCGW2)
2. Clinical progression free survival (imaging, symptoms, signs)
3. Adverse events (CTCAE v4.03)
4. Health related quality of life (EORTC QLQ C-30, PR-25 and EQ-5D-5L)
5. Health outcomes relative to costs (incremental cost effectiveness ratio)

Investigational products

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

Test 1

Comparator 2

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

Chief Operations Officer

Public contact point

Organisation

Cancer Trials Ireland

Contact name

Chief Operations Officer

Locations

1 EU/EEA country · 7 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 7 files

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

Application history

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