Terbinafine for Biochemically Recurrent Prostate Cancer (TerbinaPro)

TerbinaPro is a phase II drug-repurposing study evaluating oral Terbinafine in patients with biochemical recurrence of prostate cancer after prior local treatment with curative intent. When local salvage strategies have been exhausted, recurrence usually reflects micro-metastatic disease without clearly visible metastases on imaging. Standard therapy with androgen deprivation or androgen-receptor pathway inhibitors can effectively control disease but is associated with substantial side effects and negative impact on quality of life. Terbinafine is a long-licensed, generic antifungal drug that inhibits squalene epoxidase (SQLE), an enzyme that may play a role in prostate cancer progression. Preclinical and limited clinical data suggest potential anti-cancer activity.

Key Inclusion Criteria: * Patients after definitive treatment for localized prostate cancer and exhaustion of standard curative options (i.e. after prostatectomy and adjuvant /salvage radiotherapy; definite radiotherapy, brachytherapy; additional previous Stereotactic Body Radiation Therapy (SBRT) to treat visible oligometastatic disease also allowed as long as confirmed Prostate-specific antigen (PSA) progression is present after SBRT) * Non-castrate levels of testosterone (≥ 5 nmol/l; previous androgen deprivation therapy (ADT) allowed as long as testosterone levels have recovered before study entry) * No evidence of distant metastatic disease on conventional imaging (Computed Tomography (CT) and bone scan) or Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) CT. * Patients with PSMA positive lymph nodes on PSMA PET CT can still be included if the short axis of the largest lymph node is \< 20 mm for lymph nodes below aortic bifurcation or \< 10 mm above the aortic bifurcation. * PSA of ≥1 ng/ml after radical prostatectomy or ≥2 ng/ml above the nadir (with recovered testosterone) after primary radiotherapy; confirmation of rising PSA in at least a second measurement at least 2 weeks apart * Patient declining start of ADT and /or an androgen receptor pathway inhibitor (ARPI) and/or judged as not in need of immediate ADT/ARPI start by treating physician Key Exclusion Criteria: * Pre-existing known chronic or acute liver disease * Known history of systemic lupus erythematosus or any form of lupus (including cutaneous, drug-induced, or lupus nephritis) * Pure neuroendocrine/small-cell histologic variant of prostate cancer