Prostate Cancer
Conditions
Keywords
Angelica gigas Nakai, INM 176, pharmacokinetics
Brief summary
This study is to obtain acute dose safety and pharmacokinetics/pharmacodynamics (PK/PD) data in a dose-response trial in prostate cancer patients.
Detailed description
The long-term goal of the study is to conduct human clinical trials to test Angelica gigas Nakai (AGN) root alcoholic extract herbal supplement product (AGN-Cogni.Q, or Cogni.QTM, made with INM®176 proprietary ingredient, Quality of Life Laboratories, Purchase, NY) as a safe and potential efficacious modality for prostate cancer interception akin to secondary prevention to delay hormonal therapy or avoid it entirely after patients have developed recurrent disease following their standard of care (SOC) surgery and radiation curative treatment. The acute dose safety and pharmacokinetics (PK) and pharmacodynamics (PD) information in the target patient population from the current proposed acute PK dose-response trial will inform the optimal design and execution of the longer-term safety and efficacy (phase I/II) trials.
Interventions
DRUGAGN-Cogni.Q
Herbal dietary supplement products containing/based on AGN alcoholic extracts (including CognI.Q; Decursinol-50TM, GWB78®, Ache Action, Fast-Acting Joint Formula, EstroG-100/Profemin) are marketed in the US for memory enhancement, pain relief and for women's post-menopausal symptom management.
Sponsors
Milton S. Hershey Medical Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
After the first subject is enrolled, a 14-day waiting period must occur between each subject before the next subject can be enrolled and dosed. If one subject develops a DLT at any dose level, that subject will cease treatment but will continue safety assessments follow-ups. If a second subject develops a DLT at the same dose level, the trial will be stopped and the dose level below will be the MTD. Any subjects who are at higher dose level at the time of 2nd DLT occurrence, will also stop with no further escalation. All subjects will start at the 800 mg dose (visit 2). Each subject will continue to the next week's dose until a DLT has been reached. However, if 2 DLTs occur at the starting 800 mg dose level, trial will be suspended.
Eligibility
Sex/Gender
MALE
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willingness and ability to give informed consent. 2. Agree to comply with all study procedures and attend all study visits to the best of their ability. 3. Male with age \>=40 years. 4. History of prostate cancer diagnosis. Subjects with history of neuroendocrine or small cell prostate cancer will be excluded. Subjects are eligible if meet one or more of the below criteria: 1. Patients treated forprostate cancer and no detectable disease on imaging and clinical determination are eligible for enrollment, regardless of risk category. 2. Patients in the low-risk and favorable intermediate-risk groups who are not currently receiving any treatment or have declined any treatment. 5. Not on concurrent androgen deprivation therapy. 6. ECOG performance status 0-2. 7. Life expectancy of greater than 12 months. 8. Subjects must have normal liver and kidney function as defined below: * a) total bilirubin within normal institutional limits, * b) AST(SGOT)/ALT(SGPT) \< 2.5 X institutional upper limit of normal, * c) Creatinine within 1.5 ULN of institutional limits OR creatinine clearance \> 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal. * d) Adequate bone marrow function (Hgb ≥ 9.0 g/dL, Platelets ≥ 100 x 109/L, absolute neutrophil count (ANC) of ≥ 1.5 x 109/L), except for subjects with a history of chronic benign neutropenia, where an ANC of ≥ 1.0 x 109/L are eligible. 9. Subjects must agree to use two medically accepted method of contraception and must agree to continue use this method while on the trial and through at least one week after the last dose of study drug. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD) known to have a failure rate of less than 1% per year, or steroidal contraceptive (oral, transdermal, implanted, or injected) in conjunction with a barrier method. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) withdrawal, spermicides only, or lactational amenorrhea are not acceptable methods of contraception. 10. Subjects must stop the CYP3A4 and CYP2C19 strong inhibitors or inducers 2 weeks prior to the start of the study and during the study. 11. Subjects currently taking herbal supplements containing AGN extract, including CognI.Q, Decursinol-50, Ache Action, Fast-Acting Joint Formula, EstroG-100/Profemin must discontinue these or any other supplements containing these products 4 weeks prior to starting study drug.
Exclusion criteria
1. Subjects with distant metastatic cancer. Node positive prostate cancer patients are allowed after completion of treatment. 2. Subjects who are receiving chemotherapy, or oral TKI, or immunotherapy (checkpoint inhibitor). 3. Subjects who are receiving any other investigational agents. 4. Uncontrolled intercurrent illness that would limit compliance with study requirements. 5. All vulnerable patient populations. 6. History of New York Heart Association Class III or IV heart failure, history of a myocardial infarction within 6 months, any uncontrolled cardiac arrhythmia, or any other cardiac related problem that would be considered a contraindication for participation in the opinion of the treating physician. 7. Use of androgen deprivation therapy (ADT) or anti-androgen therapy including LHRH agonist, antagonist, GNRH analogs, and antiandrogens. 8. Subjects who are taking Warfarin/Coumadin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Safety Via Electrocardiography (EKG) | Baseline (pre-dose) and 5 hours post-dose on each dosing day and at 24 hours (Up to 5 weeks). | Evaluation of cardiac rhythm and repolarization using 12-lead EKG to identify any treatment-emergent abnormalities. Unit of Measure: Number of participants with treatment-emergent EKG abnormalities. |
| Safety Blood Laboratory Tests | 24 hours post-dose and prior to each subsequent dose level (Up to 5 weeks). | Evaluation of hematological and metabolic safety via Complete Blood Count (CBC) with differential, Comprehensive Metabolic Panel (CMP), and coagulation tests (INR, PT, PTT) to identify any treatment-emergent abnormalities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Peak Plasma Concentration (Cmax) of D, DA, and DOH | 0 to 24 hours post-dose for each dosing visit (Up to 5 weeks) | To determine the Cmax for decursin (D), decursinol angelate (DA), and their metabolite decursinol (DOH) following a single dose. Peak concentration is estimated from blood samples collected at 0, 2, 3, 4, 5, 6, 7, and 24 hours post-dose. |
| Plasma Concentration Versus Time Curve (AUC) | 0 to 24 hours post-dose for each dosing visit (Up to 5 weeks) | Area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24h) for decursin (D), decursinol angelate (DA), and their metabolite decursinol (DOH). AUC is calculated using the trapezoidal rule from blood samples collected at 0, 2, 3, 4, 5, 6, 7, and 24 hours post-dose. |
| Change From Baseline in NK, CD4+ T, and CD8+ T Cell Percentages at 24 Hours. | Baseline (0 hours) and Day 2 (24 hours post-dose). | The percentage of specific immune cell populations (NK cells, CD4+ T cells, and CD8+ T cells) within the total lymphocyte pool was measured using flow cytometric quantitation. Change is evaluated by comparing blood samples taken at Baseline (0h) to Day 2 (24 hours ± 2 hours) following administration of each AGN-CognI.Q dose. |
| Body Temperature Measurements From Baseline Through 24 Hours Post-dose | Baseline (0 hours) and 24 hours post-dose. | Body temperature was recorded to monitor safety and physiological response. Measurements were taken via tympanic thermometer at baseline (0 hours) and at 2, 3, 4, 5, 6, 7 and 24 hours (±2 hours) following the administration of each AGN-CognI.Q dose. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug to 4 weeks (± 7 days) following the last dose. | Evaluation of clinical safety and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMonika Joshi, MD
Penn State Cancer Institute
Participant flow
Pre-assignment details
This was a sequential within-subject dose-escalation study. Twelve participants received the 800 mg dose. Two participants discontinued after this period due to adverse events and did not proceed to higher doses. Ten participants continued to the 1200 mg and 1600 mg doses. Five participants enrolled during the escalation stage proceeded to the 2000 mg dose.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 66.7 years STANDARD_DEVIATION 6.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 10 | 0 / 10 | 0 / 5 |
| other Total, other adverse events | 3 / 12 | 4 / 10 | 2 / 10 | 2 / 5 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 | 0 / 10 | 0 / 5 |
Outcome results
None listed