GZ17-6.02 in Advanced CRPC After Progression on Anti-Androgen Therapy

Phase 1

Not yet recruiting

• Conditions: Castration-resistant Prostate Cancer
• Interventions: Drug: Investigational Agent Administration

• Registration Number: NCT06636123
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

The purpose of this clinical trial is to determine if GZ17-6.02 delays progression of castration-resistant prostate cancer.

Detailed Description

This single-arm phase Ib study will assess whether GZ17-6.02, a combination of curcumin, harmine, and isovanillin, delays radiographic progression of castration-resistant prostate cancer among men previously treated with androgen deprivation therapy and an androgen receptor pathway inhibitor. All participants in the study will receive GZ17-6.02. The study will also assess the safety and tolerability of GZ17-6.02 and explore patient-reported outcomes.

Study Timeline

• Study First Submitted: 2024-10-08
• Study First Submitted QC: 2024-10-08
• Study First Posted: 2024-10-10
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-06
• Last Update Posted: 2024-12-09
• Study Start: 2024-12-30
• Primary Completion: 2027-04-30
• Study Completion: 2031-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 30

Inclusion Criteria

• Patients diagnosed with prostate cancer and treated with androgen deprivation therapy (ADT) and at least one androgen receptor pathway inhibitor (ARPI) (eg, 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 ADT and ARPI treatment described
• 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 RECIST v1.1 on chest/abdomen/pelvis 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), 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/mm3.
• Platelets ≥100,000 cells/mm3.
• 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
• Ability to understand and the willingness to sign a written informed consent document

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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, 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.

• Active untreated hepatitis B or C" and "Known liver cirrhosis of any cause, active nonalcoholic steatohepatitis, or nonalcoholic fatty liver disease. Note: no additional testing necessary to confirm

• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Investigational Agent Administration	Investigational Agent Administration	GZ17-6.02: 375mg twice daily

Primary Outcome Measures

Name	Time	Method
Radiologic progression-free survival (rPFS) for 6 months or longer	6 months and up to 5 years after end of study treatment	Number of participants with rPFS for 6 months or longer

Secondary Outcome Measures

Name	Time	Method
Measure the biochemical response rate of CRPC tumors to GZ17-6.02	Up to 5 years following end of study treatment	Biochemical response measured by percentage of patients with any reduction in PSA, reduction in PSA by at least 30% (PSA30), and reduction in PSA by at least 50% (PSA50).
Measure the duration of response of CRPC tumors to GZ17-6.02	Up to 5 years following end of study treatment	Duration of tumor response, measured by time to increase in PSA.
Assess the objective response rate (ORR) in CRPC patients treated with twice daily GZ17-6.02.	Up to 5 years following end of study treatment	Best objective response (complete response, partial response, or stable disease ≥4 months) in patients with measurable disease by RECIST 1.1.
Measure the duration of radiographic response in CRPC patients treated with twice daily GZ17-6.02	Up to 5 years following end of study treatment	Duration of radiographic response
Measure overall survival (OS) in CRPC patients treated with twice daily GZ17-6.02	Up to 5 years following end of study treatment	Overall patient survival, defined as date of diagnosis to date of death
Determine the safety and tolerability of twice daily treatment with GZ17-6.02	Beginning of study treatment through the 30-day follow-up safety assessment up to 5 years	Incidence of adverse events using Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Trial Locations

Locations (1)

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States