Ignite Creation Date:
2025-12-24 @ 9:56 PM
Ignite Modification Date:
2026-01-01 @ 10:13 PM
Study NCT ID:
NCT03310632
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-09-25
First Post:
2017-10-01
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Determine Function of Antroquinonol in Combination With SOC in First Line Metastatic Pancreatic Cancer
Sponsor:
Golden Biotechnology Corporation
Organization:
Study Overview
Official Title:
A Phase I/II Study to Determine the MTD and to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Antroquinonol in Combination With SOC in First Line Metastatic Pancreatic Cancer
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Antroquinonol is proposed for the treatment of neoplasms. The proposed clinical trial is a Phase I/II study designed to evaluate antroquinonol in combination with nab-paclitaxel and gemcitabine in first line treatment naïve subjects with Stage IV metastatic pancreatic carcinoma. The first part of study will focus on the treatment of pancreatic cancer with 200 mg TID and 300 mg TID, clinical treatment duration of 4 weeks, to determine the MTD or MFD (based on PK and capsules strength) of antroquinonol in combination with a standard dose regimen of nab-paclitaxel and gemcitabine. The extended Phase II will focus on the efficacy of antroquinonol with SOC. Safety and pharmacokinetic profiles will be studied in the proposed clinical trial.
Detailed Description:
Golden Biotech are planning a Phase I/II study to determine the maximum tolerable dose (MTD) and to evaluate safety/tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of antroquinonol in combination with nab-paclitaxel-gemcitabine in first line metastatic pancreatic cancer.
Phase I
Run-in DDI and dose escalation:
The dose escalation part of the study will be conducted to characterize the safety of antroquinonol in combination with the standard of care (SOC) (nab-paclitaxel + gemcitabine) and to identify the MTD of antroquinonol in patients with metastatic pancreatic cancer. The MTD is the dose level at which \<33% (2/6) of patients experience a DLT. Within the dose escalation part of the study, a total of 6 patients will be enrolled in a run-in DDI portion to assess the effect of antroquinonol (a cytochrome P450 \[CYP\]3A4/CYP2C8 inhibitor) on the PK of paclitaxel (a CYP3A4/CYP2C8 substrate). Patients within this cohort (Cohort 1) will receive treatment as follows:
* Cycle 0 (28-day cycle): nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 (as per SOC) via intravenous (IV) infusion on Days 1, 8, and 15.
* Cycle 1 (28-day cycle): antroquinonol 200 mg administered TID on Days 1 through 28 and nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 via IV infusion on Days 1, 8, and 15.
Intense PK sampling to assess the PK of paclitaxel will be conducted in Cycles 0 and 1. The primary PK endpoints will include Cmax, AUC0-t, and AUCinf. Available bioanalytical data will be assessed in an ongoing manner to assess the effect of antroquinonol on the systemic exposure (Cmax and AUCs) of paclitaxel. Data will be reviewed by the Safety Monitoring Committee (SMC) prior to enrollment of additional patients into the dose-escalation part of the study.
For Cohort 1, the occurrence of DLTs will be assessed from Day 1 to Day 28 of Cycle 1. If ≤1 patient experiences a DLT, dosing in the dose escalation part will proceed. If ≥2 patients experience a DLT, dosing in the dose escalation part of the study will be discontinued. If ≤1 patient in Cohort 1 experiences a DLT then dosing in Cohort 2 of the dose escalation part will proceed as follows: - All Cycles: antroquinonol 300 mg administered TID on Days 1 through 28 and nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 via IV infusion on Days 1, 8, and 15 (ie, 1 cycle = weekly for 3 weeks, then 1 week off) .
Three patients will be enrolled initially into Cohort 2, these patients will be assessed for DLTs within the first 28-day dosing cycle. This cohort will be expanded to 6 total patients if 1 DLT is observed in the first 3 patients within Cohort 2. If ≤1 DLT is observed at the 300 mg dose then the 300 mg dose will be considered the MFD. If \>1 DLT is observed at the 300 mg group then 200 mg will be considered the MTD and/or the SMC will review the available data and determine the MTD/recommended dose (RD).
Patients enrolled into the dose escalation part of the study (Cohorts 1 and 2) will continue to receive treatment with antroquinonol (200 or 300 mg, respectively) in combination with nab-paclitaxel + gemcitabine in 28-day cycles at the discretion of the Investigator without a maximum duration until unacceptable toxicity or progressive disease (PD).
The total number of patients to be entered in the dose escalation part of the study will depend on the emergence of DLTs at each dose level and the total number of dose levels investigated. Up to 12 patients are planned to be treated in the dose-escalation part if no patient needs to be replaced for DLT and safety evaluation.
Phase II
Cohort expansion:
During the cohort expansion part of the study, up to an additional 40 patients will be enrolled at the MTD or MFD/RD. The dose level in the cohort expansion phase will not exceed the MTD, or highest safe dose tested in the dose-escalation phase if MTD is not reached. Patients in the cohort expansion will receive treatment as follows:
\- All Cycles: antroquinonol at the MTD or MFD/RD administered TID on Days 1 through 28 and nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 via IV infusion on Days 1, 8, and 15 (ie, 1 cycle = weekly for 3 weeks, then 1 week off) .
Patients enrolled into the cohort expansion part of the study will continue to receive treatment with antroquinonol at the MTD or MFD/RD in combination with nab-paclitaxel + gemcitabine in 28-day cycles at the discretion of the Investigator without a maximum duration until unacceptable toxicity or PD.
Phase I
Run-in DDI and dose escalation:
The dose escalation part of the study will be conducted to characterize the safety of antroquinonol in combination with the standard of care (SOC) (nab-paclitaxel + gemcitabine) and to identify the MTD of antroquinonol in patients with metastatic pancreatic cancer. The MTD is the dose level at which \<33% (2/6) of patients experience a DLT. Within the dose escalation part of the study, a total of 6 patients will be enrolled in a run-in DDI portion to assess the effect of antroquinonol (a cytochrome P450 \[CYP\]3A4/CYP2C8 inhibitor) on the PK of paclitaxel (a CYP3A4/CYP2C8 substrate). Patients within this cohort (Cohort 1) will receive treatment as follows:
* Cycle 0 (28-day cycle): nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 (as per SOC) via intravenous (IV) infusion on Days 1, 8, and 15.
* Cycle 1 (28-day cycle): antroquinonol 200 mg administered TID on Days 1 through 28 and nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 via IV infusion on Days 1, 8, and 15.
Intense PK sampling to assess the PK of paclitaxel will be conducted in Cycles 0 and 1. The primary PK endpoints will include Cmax, AUC0-t, and AUCinf. Available bioanalytical data will be assessed in an ongoing manner to assess the effect of antroquinonol on the systemic exposure (Cmax and AUCs) of paclitaxel. Data will be reviewed by the Safety Monitoring Committee (SMC) prior to enrollment of additional patients into the dose-escalation part of the study.
For Cohort 1, the occurrence of DLTs will be assessed from Day 1 to Day 28 of Cycle 1. If ≤1 patient experiences a DLT, dosing in the dose escalation part will proceed. If ≥2 patients experience a DLT, dosing in the dose escalation part of the study will be discontinued. If ≤1 patient in Cohort 1 experiences a DLT then dosing in Cohort 2 of the dose escalation part will proceed as follows: - All Cycles: antroquinonol 300 mg administered TID on Days 1 through 28 and nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 via IV infusion on Days 1, 8, and 15 (ie, 1 cycle = weekly for 3 weeks, then 1 week off) .
Three patients will be enrolled initially into Cohort 2, these patients will be assessed for DLTs within the first 28-day dosing cycle. This cohort will be expanded to 6 total patients if 1 DLT is observed in the first 3 patients within Cohort 2. If ≤1 DLT is observed at the 300 mg dose then the 300 mg dose will be considered the MFD. If \>1 DLT is observed at the 300 mg group then 200 mg will be considered the MTD and/or the SMC will review the available data and determine the MTD/recommended dose (RD).
Patients enrolled into the dose escalation part of the study (Cohorts 1 and 2) will continue to receive treatment with antroquinonol (200 or 300 mg, respectively) in combination with nab-paclitaxel + gemcitabine in 28-day cycles at the discretion of the Investigator without a maximum duration until unacceptable toxicity or progressive disease (PD).
The total number of patients to be entered in the dose escalation part of the study will depend on the emergence of DLTs at each dose level and the total number of dose levels investigated. Up to 12 patients are planned to be treated in the dose-escalation part if no patient needs to be replaced for DLT and safety evaluation.
Phase II
Cohort expansion:
During the cohort expansion part of the study, up to an additional 40 patients will be enrolled at the MTD or MFD/RD. The dose level in the cohort expansion phase will not exceed the MTD, or highest safe dose tested in the dose-escalation phase if MTD is not reached. Patients in the cohort expansion will receive treatment as follows:
\- All Cycles: antroquinonol at the MTD or MFD/RD administered TID on Days 1 through 28 and nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 via IV infusion on Days 1, 8, and 15 (ie, 1 cycle = weekly for 3 weeks, then 1 week off) .
Patients enrolled into the cohort expansion part of the study will continue to receive treatment with antroquinonol at the MTD or MFD/RD in combination with nab-paclitaxel + gemcitabine in 28-day cycles at the discretion of the Investigator without a maximum duration until unacceptable toxicity or PD.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: