Neoadjuvant Darolutamide and Relugolix Combination Preceding Radical Prostatectomy for High Risk Localized and Locally Advanced Prostate Cancer: A Phase I/Ib Trial
The goal of this clinical trial is to determine the safety and feasibility of a new combination of darolutamide and relugolix as neoadjuvant therapy preceding radical prostatectomy (RP) for high-risk prostate cancer (PCa) in adult males.
• Histologically or cytologically confirmed adenocarcinoma of the prostate
• ECOG performance status 0-1
• Ability to swallow oral medications and comply with study procedures and requirements.
• Males ≥18 years
• Participants must have adequate organ and marrow function as below:
∙ Absolute neutrophil count (ANC) ≥1,500/mm3 or ≥1.5 x 109/L;
‣ Platelets ≥100,000/mm3 or ≥100 x 109/L;
‣ Hemoglobin ≥8 g/dL (may have been transfused).
‣ Estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault equation.
‣ Total serum bilirubin \<1.5 x upper limit of normal (ULN), less than 2.0 x ULN if suspected Gilbert's syndrome;
‣ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 x ULN.
• Must be a candidate for RP
• Clinical stage cT2-4, N0-1
• Mandatory to identify tumor availability (≥10 FFPE slides, 5 µM thickness \& 1 stained H\&E slide OR tumor block)
• High-risk PCa defined as one of the following-
‣ Gleason score (GS) ≥ 4 + 3 with ≥ 6 positive systematic biopsies (SB)
⁃ GS ≥ 4 + 3 with ≥ 3 SB and prostate-specific antigen (PSA) ≥ 20 ng/mL
⁃ GS ≥ 9 in ≥ 1 SB or targeted biopsies (TB) -≥ 2 SB or TB with continuous GS ≥ 8, each with ≥ 80% involvement.