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AGN-CognI.Q Acute Dose Safety and Pharmacokinetics Dose-Response in Prostate Cancer Patients

Sponsor
Milton S. Hershey Medical Center (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05375539
Collaborator
(none)
12
Enrollment
1
Arm
12
Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Intervention Model Description:
We will follow the standard 3+3 dose escalation rule. 3 subjects will start at the first dose-level and they will stay at the same dose level as they progress in the trial. At each dose level, the dose of the following visit will be determined when the DLT is evaluated for all 3 subjects. Therefore, there can be some additional administrative wait for the first 2 subjects in the cohort. The dose level of the three subjects will be escalated to the next higher level if 0 subject among the 3 experiences DLT and deescalated to the next lower level if 2 or more subjects experience DLT. If 1 subject of the 3 experiences DLT at the dose level, a new cohort of 3 subjects will be started at this dose level. If 2 or more experience DLT out of the 6 subjects, then dose level will be deescalated to the next lower level. Dose will be escalated to the next higher level if 1 out of 6 experiences DLT. The MTD is defined as the highest dose level at which 1 or 0 experiences DLT out of 6 subjects.We will follow the standard 3+3 dose escalation rule. 3 subjects will start at the first dose-level and they will stay at the same dose level as they progress in the trial. At each dose level, the dose of the following visit will be determined when the DLT is evaluated for all 3 subjects. Therefore, there can be some additional administrative wait for the first 2 subjects in the cohort. The dose level of the three subjects will be escalated to the next higher level if 0 subject among the 3 experiences DLT and deescalated to the next lower level if 2 or more subjects experience DLT. If 1 subject of the 3 experiences DLT at the dose level, a new cohort of 3 subjects will be started at this dose level. If 2 or more experience DLT out of the 6 subjects, then dose level will be deescalated to the next lower level. Dose will be escalated to the next higher level if 1 out of 6 experiences DLT. The MTD is defined as the highest dose level at which 1 or 0 experiences DLT out of 6 subjects.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Angelica Herbal Supplement AGN-CognI.Q Acute Dose Safety and Pharmacokinetics (PK) Dose-Response in Prostate Cancer Patients (PK Dose Trial)
Anticipated Study Start Date :
Sep 1, 2022
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: AGN-CognI.Q

Dose level +1 (800 mg, 4 CognI.Q capsules, take 1-3 h after breakfast) Dose level +2 (1,200 mg, 6 CognI.Q capsules, take 1-3 h after breakfast) Dose level +3 (1,600 mg, 8 CognI.Q capsules, take 1-3 h after breakfast) Dose level +4 (2,000g, 10 CognI.Q capsules, take 1-3 h after breakfast) Dose level +4 (2,000 mg, 10 CognI.Q capsules, take within 15 min of low fat breakfast) Dose level +4 (2,000 mg, 10 CognI.Q capsules, take within 15 min of high fat breakfast)

Drug: AGN-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.
Other Names:
  • INM®176

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Electrocardiography (EKG) QTC Interval [6-8 weeks]

      Cardiac safety measured by EKG QT Interval at baseline, and at 5 hours (+/-60mins) after study drug treatment every study visit (usualy weekly) up to 8 weeks

    2. Safety blood lab tests [6-8 weeks]

      CBC diff for hematological safety and CMP for liver and kidney safety at baseline and 24 +/- 2 h after dose and before the next dose level (the latter also serves as baseline for the next dose).

    3. Clinical safety [10 weeks]

      toxicity will be evaluated using the NCI Common Toxicity Criteria (CTC) version 5.0

    Secondary Outcome Measures

    1. Peak Plasma Concentration (Cmax) [4-6 weeks]

      PK metrics of decursin (D) and its isomer decursinol angelate (DA) and their metabolite decursinol (DOH) will be measured in blood collected at pre-each dose baseline (0 h labs= baseline), 2h (+/- 30 mins), 4h (+/- 30 mins), 6h (+/-30mins) and 24 h (+/-2hrs) to estimate Peak Plasma Concentration (Cmax).

    2. Plasma Concentration versus time curve (AUC) [4-6 weeks]

      PK metrics of decursin (D) and its isomer decursinol angelate (DA) and their metabolite decursinol (DOH) will be measured in blood collected at pre-each dose baseline (0 h labs= baseline), 2h (+/- 30 mins), 4h (+/- 30 mins), 6h (+/-30mins) and 24 h (+/-2hrs) to estimate Area under the Plasma Concentration versus time curve (AUC).

    3. Peak Plasma Concentration (Cmax) [2 weeks]

      The impact of consumption of low-fat food or high fat food within 15 minutes of the highest dose or respective maximally tolerated dose (MTD) AGN-CognI.Q for each patient will be measured in blood collected from pre-each dose baseline (0 h labs= baseline), 2h (+/- 30 mins), 4h (+/- 30 mins), 6h (+/-30mins) and 24 h (+/-2hrs) to estimate Peak Plasma Concentration (Cmax).

    4. Plasma Concentration versus time curve (AUC) [2 weeks]

      The impact of consumption of low-fat food or high fat food within 15 minutes of the highest dose or respective maximally tolerated dose (MTD) AGN-CognI.Q for each patient will be measured in blood collected from pre-each dose baseline (0 h labs= baseline), 2h (+/- 30 mins), 4h (+/- 30 mins), 6h (+/-30mins) and 24 h (+/-2hrs) to estimate Area under the Plasma Concentration versus time curve (AUC).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts 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. Histologically confirmed prostate cancer diagnosis in the past. Subjects with history of neuroendocrine or small cell prostate cancer histology will be excluded.

    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:

      1. total bilirubin within normal institutional limits,
      1. AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal,
      1. Creatinine within 1.5 ULN of institutional limits OR creatinine clearance > 30 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.
      1. Adequate bone marrow function (Hgb ≥ 9.0 g/dL, Platelets ≥ 100 x 109/L, absolute neutrophil count of ≥ 1.5 x 109/L).
    1. 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.
    Exclusion Criteria:

    1. Subjects with metastatic cancer as determined by chest and abdominal CT scan, PET/CT (conventional FDG or prostate specific imaging such as AXUMIN or PSMA directed PET), MRI, bone scan within the past 12 months. Choice of imaging is per physician's discretion.

    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. Subjects currently taking herbal supplements containing AGN extract, including CognI.Q, Decursinol-50, Ache Action, Fast-Acting Joint Formula, EstroG-100/Profemin. However, they could be enrolled after discontinuation and washout for 4 weeks from the last dose.

    6. All vulnerable patient populations.

    7. 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.

    8. Use of androgen deprivation therapy (ADT) or anti-androgen therapy including LHRH agonist, antagonist, GNRH analogs, and antiandrogens.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Milton S. Hershey Medical Center

    Investigators

    • Principal Investigator: Monika Joshi, MD, Penn State Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Junxuan Lu, Professor, Milton S. Hershey Medical Center
    ClinicalTrials.gov Identifier:
    NCT05375539
    Other Study ID Numbers:
    • PSCI-21-173
    First Posted:
    May 16, 2022
    Last Update Posted:
    May 16, 2022
    Last Verified:
    May 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Junxuan Lu, Professor, Milton S. Hershey Medical Center
    Angelica gigas Nakai
    INM 176
    pharmacokinetics
    Additional relevant MeSH terms:
    Prostatic Neoplasms

    Study Results

    No Results Posted as of May 16, 2022