Evaluate Safety and Efficacy of Daily Oral Angelica Gigas Nakai (AGN)-INM176 in Prostate Patients With Rising Plasma PSA (Phase I/II Trial)
Summary
This Phase I/II open-label trial aims to evaluate the safety and efficacy of the herbal supplement INM176 in patients with a history of prostate cancer or low-risk disease under active surveillance. The study will determine the recommended Phase II dose (RP2D) and assess the efficacy of INM176 in stabilizing or decreasing plasma PSA levels in post-radical prostatectomy (RP) and post-radiation therapy (RT) patients with rising PSA levels.
Detailed description
The study is designed as a Phase I/II open-label trial to assess the safety and preliminary efficacy of the herbal supplement INM176 in intercepting prostate cancer-specific PSA levels. The primary objective of the Phase I stage is to determine the recommended Phase II dose (RP2D) through a 3+3 dose escalation design while evaluating the safety of INM176 during a 4-week cycle for dose-limiting toxicities (DLTs) in patients with a history of prostate cancer or those under active surveillance for low-risk disease. In the Phase II stage, the primary objective is to evaluate the efficacy of INM176 at the RP2D in stabilizing or reducing plasma PSA levels after six cycles of treatment in post-RP and post-RT patients experiencing a rise in PSA. Secondary objectives include pharmacokinetic (PK) evaluations following the first dose (Cycle 1 Day 1) in both Phase I and Phase II subjects, with an additional PK assessment on Cycle 1 Day 28 for Phase I subjects and on Cycle 2 Day 1 for Phase II subjects. Acute and chronic exposure PK parameters (including Cmax and AUC) will be correlated with safety outcomes and prostate-specific antigen (PSA) efficacy measures, when applicable, stratified by CYP2C19 and CYP3A4 metabolizer status. Additional secondary objectives include evaluation of PSA change from baseline at protocol-specified timepoints; immunophenotyping of blood natural killer (NK) cells and other immune cell subsets; assessment of NK functional activity, plasma IL-8, and select cytokines; and measurement of male hormones and hormone-binding proteins. These pharmacodynamic biomarkers will be analyzed in relation to PSA response and PK metrics, with assessments conducted according to Phase I and Phase II study schedules.
Arms & interventions
- DrugINM176
The active ingredient INM176 was prepared using a proprietary technology to extract AGN with ethanol and powderize with cellulose into a finished granular powder product that is 1/5 the weight of the raw herbal root. This product was chosen because its close match with the AGN extracts studied in the TRAMP model in the phytochemical profiles. It will be donated from the manufacturer Nutragen Co., Ltd. Korea.
Outcome measures
Primary
Safety of INM176 after 1, 2, 3,4, 5, and 6 cycles of exposure at RP2D
Safety will be assessed as the combined incidence of adverse events, abnormal safety blood tests, and abnormal ECG readings, expressed as the proportion of participants showing any of these safety concerns following 1, 2, 3, 4, 5, and 6 treatment cycles.
Time frame: 10 months
Efficacy of INM176 by Measuring PSA Level Changes After 6 Cycles of Treatment at the Recommended Phase II Dose (RP2D)
This outcome will assess the efficacy of INM176 by measuring changes in Prostate-Specific Antigen (PSA) levels from baseline to after 6 cycles of treatment at the Recommended Phase II Dose (RP2D). PSA levels will be monitored at baseline and following each treatment cycle, with a primary focus on the change observed after 6 cycles. The degree of PSA reduction will serve as an indicator of INM176's effectiveness in controlling or reducing prostate cancer activity.
Time frame: 10 months
Maximum Tolerated Dose (MTD)
The Maximum Tolerated Dose (MTD) is defined as the highest dose at which ≤1 of 6 participants experiences a dose-limiting toxicity (DLT) during Cycle 1 (28 days). Dose-limiting toxicities will be assessed according to CTCAE version 5.0.
Time frame: 28 days
Recommended Phase II Dose (RP2D)
The Recommended Phase II Dose (RP2D) will be determined based on overall safety and tolerability, observed dose-limiting toxicities, following dose escalation using a standard 3+3 design.
Time frame: 28 days
Dose-Limiting Toxicities (DLTs)
Dose-Limiting Toxicities (DLTs) are defined as adverse events or laboratory abnormalities that are considered to be related to the study treatment and occur during the first treatment cycle (28 days). DLTs will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The occurrence of DLTs will guide dose escalation decisions and help identify the Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D).
Time frame: 28 days
Eligibility criteria
Study locations (1)
Penn State Cancer Institute
Hershey, Pennsylvania, 17033