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

Официальное название

GZ17-6.02 in Advanced Castration-Resistant Prostate Cancer (CRPC) After Progression on Anti-Androgen Therapy

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Investigational 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

Первичные конечные точки

• Radiologic progression-free survival (rPFS) for 6 months or longer [Срок оценки: 6 months and up to 5 years after end of study treatment]

Вторичные конечные точки (6)

• Measure the biochemical response rate of CRPC tumors to GZ17-6.02 [Срок оценки: Up to 5 years following end of study treatment]
• Measure the duration of response of CRPC tumors to GZ17-6.02 [Срок оценки: Up to 5 years following end of study treatment]
• Assess the objective response rate (ORR) in CRPC patients treated with twice daily GZ17-6.02. [Срок оценки: Up to 5 years following end of study treatment]
• Measure the duration of radiographic response in CRPC patients treated with twice daily GZ17-6.02 [Срок оценки: Up to 5 years following end of study treatment]
• Measure overall survival (OS) in CRPC patients treated with twice daily GZ17-6.02 [Срок оценки: Up to 5 years following end of study treatment]
• Determine the safety and tolerability of twice daily treatment with GZ17-6.02 [Срок оценки: Beginning of study treatment through the 30-day follow-up safety assessment up to 5 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Virginia Commonwealth University — Richmond

Идентификаторы

NCT: NCT06636123 · MCC-23-20417 · HM20030070

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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