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Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Antroquinonol will first be conducted by dose escalation(200mg TID and 300mgTID) 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.

At the cohort expansion part of the study, up to an additional 40 patients will be enrolled at the MTD or MFD/RD.

Antroquinonol: 100 mg and corn oil 100 mg encapsulated in a gelatin capsule administered orally. Dose will be selected(200mg TID or 300mg TID with SOC) after phase I, then follow up the best dose for 40 Patients for the efficacy.

Antroquinonol

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.

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:

Six patients will be enrolled in the run-in DDI cohort of the dose-escalation part of the study (ie, Cohort 1) and 3 to 6 patients may be enrolled in Cohort 2. The total number of patients to be entered in the dose-escalation part of this study will depend on the emergence of DLTs at each dose level, but will be up to 12 if no replacement occurs at the 2 predefined dose levels.

Phase II

Cohort expansion:

Up to an additional 40 patients may be enrolled at the MTD or MFD/RD. A power calculation was not employed to determine the sample size of the study, as this is aproof of concept study with a preliminary assessment of anti-tumor activity of antroquinonol in combination with nab-paclitaxel + gemcitabine in metastatic pancreatic cancer patients.

Determine Function of Antroquinonol in Combination With SOC in First Line Metastatic Pancreatic Cancer

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

The MTD is the dose at which \<33% of patients experience a dose limiting toxicity (DLT) within the first 28-day cycle of antroquinonol and nab-paclitaxel

+ gemcitabine combined treatment

measure patient's weight and height and calculated by {\[Height (cm) × Adjusted Body Weight\] × 1/3,600}\^1/2

maximum observed plasma concentration of antroquinonol and paclitaxel

Plasma concentrations of antroquinonol and paclitaxel will be measured and PK parameters calculated where applicable.

blood will be draw and measured. Other emerging antroquinonol biomarkers may be evaluated.

Medical Doctors judged the patient's performance status

Spots Global Cancer Trial Database for hocena

Every month we try and update this database with for hocena cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hocena

Every month we try and update this database with for hocena cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hocena cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.