GZ17-6.02 for the Treatment of Patients with Progressive, Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• Adults (age ≥ 18 years) diagnosed with metastatic prostate cancer and treated with androgen deprivation therapy (ADT) and at least one androgen receptor pathway inhibitor (ARPI) (e.g., abiraterone, enzalutamide, apalutamide or darolutamide). Previous prostate specific membrane antigen (PSMA)-targeted therapy or cytotoxic chemotherapy is allowed but not required
• Androgen levels ≤ 50 ng/dL (≤ 1.73 nmol/L)
• Disease progression following treatment
• Prostate specific antigen (PSA) progression over 2 assessments, defined as rising PSA values from 2 consecutive assessments with an interval of at least 7 days between assessments. PSA levels prior to study enrollment are considered and appropriate for inclusion
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 on chest/abdomen/pelvis computed tomography (CT) or evaluable disease observed on bone scan
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Appropriate hepatic function defined by a total bilirubin (TBL) ≤ 1.5 × the upper limit of normal (ULN) at screening
• Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) ≤ 3 × ULN at screening
• Appropriate kidney function defined by calculated or actual creatinine clearance ≥ 30 mL/min
• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3
• Platelets ≥ 100,000 cells/mm^3
• Serum hemoglobin level ≥ 9 g/dL
• Agree to not donate blood or sperm during the study and for 90 days after the last dose of study treatment
• Patients with sexual partners of childbearing potential must agree to use highly effective methods of contraception throughout the study. Highly effective methods include the following: * Subdermal contraceptive implants * Intrauterine devices (IUDs) * Bilateral tubal occlusion * Vasectomy * Sexual abstinence * Two lower efficacy methods can also be combined to be considered highly effective (i.e., birth control pills and condoms) Patients should continue to use highly effective methods of contraception for 6 months after study treatment ends. Childbearing potential excludes: * Age > 50 years and naturally amenorrhoeic for > 1 year OR * previous hysterectomy or bilateral salpingo-oophorectomy
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Any investigational agent: * Within 4 weeks OR * Within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, before initiating study treatment
• Low PSA (≤ 10 ng/mL) at initial presentation (before ADT or at symptomatic progression in the castrate setting) plus high volume (≥ 20) bone metastases
• Simultaneous enrollment in any other cancer treatment interventional clinical trial
• Active untreated hepatitis B or C
• Known liver cirrhosis of any cause, active nonalcoholic steatohepatitis, or nonalcoholic fatty liver disease Note: no additional testing necessary to confirm
• Active, uncontrolled diarrhea leading to dehydration or electrolyte disturbances not controlled with oral repletion
• Grade ≥ 3 uncontrolled infection
• Major surgery (in the opinion of the treating investigator) ≤ 3 weeks before initiating study treatment
• Not having fully recovered to a grade of 1 or lower from any surgery-related adverse effects within the 3 weeks preceding the start of the study treatment
• Small cell, anaplastic, or neuroendocrine component
• Known active brain metastasis
• Known active leptomeningeal disease
• Planned ongoing treatment with other drugs thought to potentially have adverse interactions with either of the medications included in the study treatment must be discontinued ≥ 2 weeks prior to initiating study treatment unless otherwise noted: * Monoamine oxidase inhibitors (MAOI) use; must discontinue use 10 days prior to initiating study therapy. * Strong or moderate CYP1A2, CYP3A4 and CYP2C19 inhibitors. * Rucaparib, Olaparib and Talazoparib, due to their common findings of liver enzyme elevation
• Inability to swallow medication
• Known hypersensitivity to GZ17-6.02 components (curcumin, harmine, and isovanillin) or excipients
• Known or suspected malabsorption condition or obstruction
• Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient’s risk or limit the patient’s adherence with study requirements