Study Evaluating the Efficacy and Safety of Darolutamide and Stereotactic Dose Escalated Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse

Launched by UNICANCER · Oct 2, 2024

Keywords

ClinConnect Summary

The PEACE 7 trial is a research study designed to evaluate the effectiveness and safety of two treatments—darolutamide and a type of targeted radiation therapy—combined with hormone therapy for men with localized prostate cancer who are at high risk of recurrence. The main goal is to see how well these treatments help prevent cancer from spreading. Participants in the study will be randomly assigned to one of four groups, where they will receive different combinations of hormone therapy, standard radiation, and the experimental treatments over a period of two years. Regular check-ups will be scheduled to monitor their health and prostate-specific antigen (PSA) levels, which can indicate cancer activity.

To join the study, participants must be men aged 18 to 80 with confirmed prostate cancer that meets certain high-risk criteria, such as having a high Gleason score or elevated PSA levels. They should also be in good overall health, without serious medical conditions that could interfere with the study. Throughout the trial, participants will receive close medical supervision and support, ensuring they understand the treatment process and any potential side effects. This study offers a chance to explore new treatment options that might improve outcomes for men with prostate cancer.

Gender

MALE

Eligibility criteria

• Inclusion Criteria:
• • 1. Signed a written informed consent form prior to any trial specific procedures
• • Note: In case of physical incapacitation, a trusted representative of their choice, which is not the investigator or sponsor, can sign on the behalf of the patients
• • 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:
• • Gleason score ≥8
• • T3 or T4 disease (T3 defined by MRI is acceptable)
• • Prostate-specific antigen ≥20 ng/mL
• • 7. Prostate size on MRI \<100 cc
• • 8. Absolute neutrophil count ≥ 1.5 x 10⁹/L
• • 9. Platelet count ≥100 x 10⁹/L
• • 10. Haemoglobin ≥90 g/L (in absence of red blood cell transfusion within 4 weeks prior to randomization)
• • 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:
• • 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 Note: Patients with infra-centimetric nodal disease (\<1 cm in small diameter) on conventional imaging and equivocal hyperfixation on next generation imaging may be included
• • 2. Recent history of TURP or prostate enucleation (less than 6 months) Note: patients with severe obstructive symptoms (defined as International Prostate Symptom Score (IPSS) ≥20) should be carefully evaluated to rule out the need for TURP/Prostate enucleation
• • 3. Prior treatment for prostate cancer, including prostatectomy, except lymph node dissection (patients with PN- disease only can be accrued) or ADT (started more than 6 weeks before randomization)
• • 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 malignancy 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 randomization
• • 18. Prior chemotherapy or immunotherapy for prostate cancer
• • 19. Major surgery within 28 days before randomization
• • 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