Clinical trial NCT06636123: GZ17-6.02 in Advanced CRPC After Progression on Anti-Androgen Therapy
Official title: GZ17-6.02 in Advanced Castration-Resistant Prostate Cancer (CRPC) After Progression on Anti-Androgen Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Castration-resistant Prostate Cancer
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2024-10-10
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Radiologic progression-free survival (rPFS) for 6 months or longer
timeFrame: 6 months and up to 5 years after end of study treatment
Secondary outcomes:
measure: Measure the biochemical response rate of CRPC tumors to GZ17-6.02
timeFrame: Up to 5 years following end of study treatment
measure: Measure the duration of response of CRPC tumors to GZ17-6.02
timeFrame: Up to 5 years following end of study treatment
measure: Assess the objective response rate (ORR) in CRPC patients treated with twice daily GZ17-6.02.
timeFrame: Up to 5 years following end of study treatment
measure: Measure the duration of radiographic response in CRPC patients treated with twice daily GZ17-6.02
timeFrame: Up to 5 years following end of study treatment
measure: Measure overall survival (OS) in CRPC patients treated with twice daily GZ17-6.02
timeFrame: Up to 5 years following end of study treatment
measure: Determine the safety and tolerability of twice daily treatment with GZ17-6.02
timeFrame: Beginning of study treatment through the 30-day follow-up safety assessment up to 5 years
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: John Melson, MD
role: PRINCIPAL_INVESTIGATOR
References: