Treatment with darolutamide +/- radiation therapy for patients with a castration resistant cancer and metastases detected by functional imaging

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Feb 2025 → ongoing

Decision date (initial)

2024-05-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bayer AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objective of this study is to assess the efficacy of darolutamide and of a stereotactic dose escalated radiotherapy targeting prostate in combination with ADT and pelvic nodal
radiotherapy in terms of metastasis-free survival (MSF), in patients with localised prostate cancer and high-risk features of relapse (defined as patients having at least 2 high-risk criteria from the NCCN classification) in a 2 by 2-factorial trial.

Secondary objectives 8

1. To assess the efficacy of the treatments in terms of Clinical progression-free survival (cPFS)
2. To assess the efficacy of the treatments in terms of Biochemical progression-free survival
3. To assess the efficacy of the treatments in terms of Time to local relapse
4. To assess the efficacy of the treatments in terms of Overall survival (OS)
5. To assess the efficacy of the treatments in terms of Prostate cancer-specific survival (PCSS)
6. To assess the safety of the treatments in terms of acute toxicity
7. To assess the safety of the treatments in terms of long-term toxicity
8. To determine the impact of treatments on patients’ quality of life

Conditions and MedDRA coding

Patients with localised prostate cancer and high-risk features of relapse (minimum 2 high-risk criteria from National Comprehensive Cancer Network (NCCN) classification)1 and with no detectable metastasis, including no evidence of pelvic lymph node metastasis on next-generation imaging (PSMA PET/CT).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Signed a written informed consent form prior to any trial specific procedures
2. Men, 18 years ≤ Age ≤ 80 years
3. ECOG performance status of 0 or 1
4. No significant co-morbidities that might prevent long-term follow-up
5. Histologically confirmed adenocarcinoma of the prostate
6. Meet at least 2 of the following criteria from NCCN classification
7. Prostate size on MRI < 100 cc
8. Absolute neutrophil count ≥ 1.5 x 10^9/L
9. Platelet count ≥ 100 x 10^9/L
10. Haemoglobin ≥ 90 g/L (in absence of red blood cell transfusion within 4 weeks prior to randomisation)
11. Hepatic function: serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN
12. Creatinine ≤ 2.0 x ULN
13. Sexually active patients must agree to use an effective contraceptive method while on treatment and for 1 week after the final dose of investigational product
14. Patient must be affiliated to a Social Security System or in possession of equivalent private health insurance (according to local regulations for participation in clinical trials)
15. Patient must be willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow- up

Exclusion criteria 22

1. Clinically or radiologically detectable metastasis, including no evidence of pelvic lymph node metastasis on next generation imaging (PSMA PET/CT), nor enlarged pelvic lymph nodes (≥ 1 cm in small diameter) on MRI.
2. Recent history of TURP or prostate enucleation (less than 6 months)
3. Prior treatment for prostate cancer except lymph node dissection (i.e. patients with PN- disease only can be included) or ADT (started more than 6 weeks before randomisation).
4. Patient with other known concurrent severe and/or uncontrolled concurrent medical disease or infection (such as active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease) or co-morbidity, which could compromise participation in the study.
5. Cardiac disease such as uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg; 3 consecutive measures taken 5 minutes apart), stroke, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, coronary/peripheral artery bypass graft, LVEF > grade 2,
6. Uncontrolled diabetes mellitus
7. Current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment)
8. Gastrointestinal disorder or procedure, which expects to interfere significantly with absorption of study treatment. Severe GI disorders precluding pelvic irradiation
9. Known severely impaired lung function (spirometry and DLCO 70% or less of normal and O2 saturation of 88% or less at rest on room air)
10. Other prior malignancies within the last 3 years, except basal cell skin cancer
11. Known hypersensitivity to the study treatment or any of its ingredients
12. Physical or psychological condition or any condition that in the opinion of the investigator would impair the patients' ability to comply with the study procedures
13. Previous treatment for prostate cancer (surgery or radiotherapy) or previous pelvic irradiation that would make prostate/pelvis radiotherapy impossible
14. Concomitant prohibited treatment. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5. A one-week washout period is necessary for patients who are already on these treatments
15. Prior treatment with second generation androgen receptor (AR) inhibitors, other investigational AR inhibitors, or CYP17 enzyme inhibitor
16. Use of oestrogens or 5-α reductase inhibitors or AR inhibitors
17. Acute toxicities of prior treatments and procedures not resolved to grade ≤ 1 or baseline before randomisation.
18. Prior chemotherapy or immunotherapy for prostate cancer.
19. Major surgery within 28 days before randomisation
20. Participation in another therapeutic trial within 30 days prior to inclusion
21. Persons deprived of their liberty or under protective custody or guardianship
22. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Metastasis-free survival (MFS)

Secondary endpoints 8

1. Clinical Progression-Free Survival (cPFS)
2. Biochemical Progression-Free Survival
3. Time to local relapse
4. Overall Survival (OS)
5. Prostate Cancer-Specific Survival (PCSS)
6. Severity of the adverse events and toxicities
7. Long-term toxicity
8. Quality of Life

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Director of Regulatory Affairs,Pharmacovigilance and Quality Insurance

Public contact point

Organisation

Unicancer

Contact name

Director of Regulatory Affairs,Pharmacovigilance and Quality Insurance

Locations

2 EU/EEA countries · 46 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 17 files

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

Application history

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