Castration-resistant Prostate Cancer
Conditions
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.
Interventions
DRUGInvestigational Agent Administration
GZ17-6.02 will be taken orally with a high-fat meal at a fixed dose of 375 mg twice daily each day of a 28-day cycle, continuing until progression or intolerable toxicity
Sponsors
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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 ≥8 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
CONTACTMassey IIT Research Operations
PRINCIPAL_INVESTIGATORJohn Melson, MD
Virginia Commonwealth University
Outcome results
None listed