A clinical research study to investigate whether the addition of a new medication (darolutamide) to standard treatment is better for improving the outcomes for men with localised prostate cancer compared to standard treatment.
- Conditions
- Clinically localised prostate cancer defined as very high risk, or with very high risk features.MedDRA version: 20.0Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004818-34-IE
- Lead Sponsor
- Cancer Trials Ireland
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 1100
1. Men aged 18 years and older, with pathological diagnosis of adenocarcinoma of the prostate.
2. EITHER planned for primary RT and judged to be at very high risk for recurrence based on any of the following:
- Grade Group 5, OR
- Grade Group 4 AND one or more of the following: clinical T2b-4 OR MRI with seminal vesicle invasion OR extracapsular extension OR PSA* > 20ng/mL, OR
- Pelvic nodal involvement (involvement of lymph nodes (LNs) at or below the bifurcation of the aorta into the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if = 10mm)
OR
Post-radical prostatectomy = 365 days prior to randomisation and planned for RT with PSA = 0.1 ng/mL that has risen or remained stable (within = 0.05 ng/mL) since a previous level at least 1 week earlier, judged to be at very high risk for recurrence based on any of the following:
- Grade Group 5, OR
- Grade Group 4 AND pT3a or higher, OR
- Pelvic nodal involvement (involvement of LNs at or below the bifurcation of the aorta into the common iliac arteries) defined radiologically as greater than 10mm on short axis using standard CT or MRI, or pathologically confirmed (PSMA PET alone is not considered enough if = 10mm)
* Screening PSA levels are those measured within 240 days prior to randomisation.
3. Adequate bone marrow function: Haemoglobin = 100g/L, white cell count (WCC) = 4.0x10^9/L, absolute neutrophil count (ANC) = 1.5x10^9/L and platelets > 100 x 10^9/L
4. Adequate liver function: alanine aminotransferase (ALT) < 2 x upper limit of normal (ULN) and total bilirubin < 1.5 x ULN, (or if total 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. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
7. Study treatment both planned and able to start within 7 days after randomisation
8. Willing to complete health-related quality of life (HRQL) questionnaires UNLESS is unable to complete because of literacy or limited vision
9. Willing and able to comply with all study requirements, including standard of care treatment such as EBRT, timing and/or nature of required assessments
10. Signed, written informed consent
Additional:
Conventional imaging must be used to confirm eligibility and disease progression, PSMA PET alone is not considered enough.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40
11. Prostate cancer with predominant non-adenocarcinoma features(sarcomatoid/spindle cell/neuroendocrine small cell/squamous cell components/other non-adenocarcinoma)
12. Involvement of LNs by conventional CT imaging superior to the common iliac artery bifurcation,and/or outside the pelvis(distant LNs).LN involvement is defined by histopathological confirmation,or by a short axis measurement > 10mm on standard imaging(CT or MRI,but not PET).
13. Evidence of metastatic disease. Minimum imaging requirements to exclude metastatic disease are defined in the trial protocol.
• If endocrine therapy (ET)had not started,imaging must be within 60 days prior to randomisation.
• If ET has been started,radiographic imaging (CT/MRI/CXR)must have been performed no more than 60 days prior to starting ET&no more than 30 days after starting ET &prior to randomisation. Refer to protocol for further detail.
14. PSA >100 ng/mL at any time.
15. Any prior use of new generation potent AR inhibition(abiraterone,enzalutamide,apalutamide,darolutamide or similar agents).
16. Prior endocrine therapy for prostate cancer except for the following,which are allowed:
• (i)LHRHA and/or(ii)a first-generation nonsteroidal antiandrogen(NSAA)are allowed if commenced no more than 90 days before randomisation.If an NSAA has been used,it must be stopped before starting study treatment with darolutamide/placebo; and
• Prior use of 5-alpha reductase inhibitor is allowed&if used,it must be stopped before starting study treatment with darolutamide/placebo.
17. Bilateral orchidectomy
18. Prior pelvic brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields that would preclude the required RT
19. History of
• Loss of consciousness or transient ischemic attack or stroke within 6 months prior to randomisation,or
• Significant cardiovascular disease within 6 months prior to randomisation:including myocardial infarction,unstable angina,congestive heart failure(NYHA grade II or greater),ongoing arrhythmias of Grade >2(CTCAE v5.0),thromboembolic events,coronary artery bypass graft.Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
20. Known gastrointestinal disease/procedure that could interfere with the oral absorption or tolerance of darolutamide,including difficulty swallowing tablets
21. History of another malignancy within 5 years prior to randomisation except for those malignancies treated with curative intent with a predicted risk of relapse of less than 10% including but not limited to non-melanoma carcinoma of the skin;or adequately treated,non-muscle-invasive urothelial carcinoma of the bladder(i.e.Tis, Ta &low grade T1 tumours).
All such cases with a history of malignancy within the last 5 years are to be discussed with study team before randomisation. Melanoma in-situ&other adequately treated in-situ neoplasms are not considered malignancies for the purposes of eligibility assessment.
22. Concurrent illness,including severe infection that might jeopardise the ability of the participant to undergo the procedures outlined in the protocol with reasonable safety(HIV infection is not an exclusion criterion if it is controlled with anti-retroviral drugs that are unaffected by concomitant darolutamide)
23. Presence of any psychological,familial,sociological or geographical condition potentially hampering compliance with the study protocol &follow-up schedule,including alcohol dependence or drug abuse
24. Pa
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method