Trial Title:
Safety and Efficacy of AGN-INM176 in Prostate Patients With Rising PSA
NCT ID:
NCT06600698
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Conditions: Keywords:
Angelica gigas Nakai
INM 176
Pharmacokinetics
Decursin
decursinol
prostate specific antigen (PSA)
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
This is a one-arm, sequential Phase I/II study to evaluate INM176. Phase I uses a 3+3
dose escalation design to find the recommended Phase 2 dose (RP2D) based on dose-limiting
toxicities. Phase II includes two stages: Stage 1 involves 13 subjects to test early
efficacy; if ≥1 responds (PSA decline/stabilization), the study moves to Stage 2. Stage 2
enrolls 14 more subjects (total 27) to assess efficacy. A PSA response rate >5% is
declared if ≥4 subjects show response. Safety and efficacy will be evaluated with
descriptive statistics, linear mixed-effects models, and regression analyses for PK and
biomarkers.
Intervention Type: Drug
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
INM176
Description:
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.
Arm group label:
INM176 Dose Escalation and Tolerability Assessment in phase I and efficacy assessment in phase II
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 pharmacokinetics (PK) analysis on the first and last doses
of Cycle 1, correlating PK metrics to safety and efficacy outcomes, stratified by CYP2C19
and 3A4 metabolizer status. Additional secondary measures involve assessing PSA changes,
immunophenotyping of blood natural killer (NK) cells, NK functional activity, cytokine
levels, and hormone-binding proteins, all analyzed as pharmacodynamic (PD) biomarkers.
These results will inform the design of future large-scale randomized controlled trials
(RCTs) investigating the efficacy of INM176 in delaying or preventing prostate cancer
recurrence.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Phase I 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 aged >=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 they meet one
or more of the below criteria:
4a. Subjects with treated prostate cancer are eligible. 4b. Subjects with localized
prostate cancer in low-risk group who were not on treatment or declined any treatment are
eligible.
4c. Subjects with localized prostate cancer in the favorable intermediate-risk group who
declined any treatment are eligible.
5. Subjects must not be undergoing concurrent radiation therapy or androgen deprivation
therapy (ADT) at the time of enrollment.
6. ECOG performance status 0-2. 7. 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 of ≥ 1.0 x 109/L).
8. Subjects and their partners must agree to use two medically accepted methods of
contraception and must agree to continue use these methods during the trial and
for 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.
9. Subjects taking strong inhibitors or inducers of CYP3A4 or CYP2C19 must be
evaluated for potential drug interactions with the study drug. Essential
medications, such as statins, that cannot be discontinued may be allowed if
deemed safe and appropriate by the investigator, or if an alternative
medication can be substituted.
10. Subjects currently taking herbal supplements containing AGN extract, such as
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.
Phase II 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 aged >=40 years.
4. Histologically confirmed adenocarcinoma of Prostate. Subjects with history of
neuroendocrine or small cell prostate cancer must be excluded.
5. Any T stage, N0-1, M0, any Gleason grade.
6. Subjects with treated prostate cancer, either post-radical prostatectomy (RP) or
post-radiation therapy (RT). Subjects who have local recurrence in the prostate
after treatment but decline further intervention are also eligible.
OR Subjects with localized prostate cancer (no distant or nodal metastases) who have
declined any treatment after discussion with their treating physician.
7. No distant metastases disease confirmed by imaging (CT or MRI and bone scan or
prostate-specific PET scan such as PSMA PET scan or Axumin PET scan).
8. Blood PSA level rising over 2 consecutive tests within the past 6 months, at least
one week apart.
9. Not currently receiving concurrent androgen deprivation therapy, and testosterone
levels should be within a non-castrate range (normal or at least >50 ng/dL).
10. ECOG performance status 0-2.
11. Subjects must have normal liver and kidney function as defined below:
1. total bilirubin within normal institutional limits,
2. AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal (ULN),
3. 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,
4. Adequate bone marrow function (Hgb ≥ 9.0 g/dL, Platelets ≥ 100 x 109/L,
absolute neutrophil count of ≥ 1.0 x 109/L).
12. No evidence of any active secondary malignancy requiring ongoing treatment.
13. 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.
14. Subjects taking strong inhibitors or inducers of CYP3A4 or CYP2C19 must be evaluated
for potential drug interactions with the study drug. Essential medications, such as
statins, that cannot be discontinued may be allowed if deemed safe and appropriate
by the investigator, or if an alternative medication can be substituted.
15. 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 systemic treatments such as chemotherapy, androgen
deprivation therapy (ADT) or anti-androgen therapy including LHRH agonist,
antagonist, GNRH analogs, and antiandrogens, or immunotherapy (checkpoint
inhibitor).
3. Subjects who are receiving any other investigational agents. Participants will be
excluded if they have any uncontrolled intercurrent illness at the discretion of the
treating investigator. This may include, but is not limited to, the following
conditions: ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes mellitus (DM)
with an HbA1C >9, uncontrolled asthma, or psychiatric illness/social situations that
would limit compliance with study requirements.
4. History of New York Heart Association Class III or IV heart failure, history of a
myocardial infarction within 6 months, or any other cardiac-related problem that
would be considered a contraindication for participation in the opinion of the
treating physician.
5. Any active secondary malignancy requiring treatment.
6. Chronic kidney disease with calculated GFR <30 mL/min/1.73 m2 using Cockcroft-Gault
formula, or measured GFR <30 mL/min/1.73 m2 using a 24-hour urine collection. The
hospital's lab measured GFR can be used if a 24-hour collection is not possible.
7. Subjects who are taking Warfarin/coumadin.
Gender:
Male
Gender based:
Yes
Gender description:
Participant eligibility is based on self-representation of gender identity.
Minimum age:
40 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
January 1, 2025
Completion date:
January 1, 2028
Lead sponsor:
Agency:
Milton S. Hershey Medical Center
Agency class:
Other
Source:
Milton S. Hershey Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06600698
