Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

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

Covance

Golden Biotechnology Corporation

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Pleural Effusion

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression, unacceptable toxicity, non compliance or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever comes first.

Howard Cheng, Ph.D.

This is a single arm, open label, Phase II study in KRAS-positive and KRAS-negative patients with stage IV (including pleural effusion) non squamous NSCLC who have failed two lines of anti-cancer therapy. A maximum of 60 evaluable patients with NSCLC will receive antroquinonol, of which 30 patients will be KRAS-positive and 30 patients KRAS-negative. An evaluable patient will have received at least one dose of antroquinonol and have a valid baseline tumor assessment. Enrollment will continue until the target number of evaluable patients has been enrolled.

1. Progression free survival rate at 12 weeks, defined as the proportion of patients alive and progression free at Week 12. Patients will be progression free if they have no tumor assessments of progressive disease (defined according to RECIST guidelines, version 1.1) at any point from the start of treatment to Week 12.
2. Objective response rate (ORR), defined as the proportion of patients whose best overall response is either CR or PR according to RECIST version 1.1. The best overall response is the best response recorded during the first 12 week treatment cycle.
3. Disease control rate (DCR), defined as the proportion of patients with a documented CR, PR and SD during the first 12 week treatment cycle according to RECIST version 1.1.
4. Duration of overall tumor response (DR), defined as the interval between the date of the first observation of tumor response (CR or PR) and the date of disease progression or death.
5. Progression free survival defined as the time from randomization to objective tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first.
6. Overall survival (OS) defined as the time from randomization to death from any cause.
7. Time to progression (TTP) defined as the time from randomization to objective tumor progression by RECIST version 1.1.

Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC

A Single-Arm, Open-Label, Phase II Trial Evaluating the Efficacy, Safety and Pharmacokinetics of Antroquinonol in Patients With Stage IV (Including Pleural Effusion) Non Squamous NSCLC Who Have Failed Two Lines of Anti-Cancer Therapy

Defined as the proportion of patients whose best overall response is either CR or PR according to RECIST version 1.1. The best overall response is the best response recorded during the first 12 week treatment cycle.

the time from the date of first administration of study drug to death from any cause

Tumor response will be assessed at 6 week intervals during the first treatment cycle using the RECIST criteria, version 1.1. Each patient will be assigned one of the following categories: 1) complete response (CR), 2) partial response (PR), 3) stable disease (SD), or 4) progressive disease (PD). Patients who died from any cause or discontinued the study for any reason without a post screening or Week 12 tumor assessment will be considered as failing to respond to treatment.

PK sampling will be performed on Days 0 and 28 in all patients enrolled in Stage 1.PK endpoints will be derived for intensively sampled PK profiles by non compartmental methods and include: Cmax: peak concentration;Ctrough: trough plasma concentration.

the proportion of patients with a documented CR, PR and SD during the first 12 week treatment cycle according to RECIST version 1.1.

PK sampling will be performed on Days 0 and 28 in all patients enrolled in Stage 1.PK endpoints will be derived for intensively sampled PK profiles by T½: terminal half life

ICON Clinical Research

Patients were followed for AEs from the date of informed consent until resolution or stabilization, alternative treatment for NSCLC was started 6 months after last dose of study drug, or loss to follow-up, whichever occurred first. In the event of serious or study drug-related toxicities, the patient was followed until resolution or stabilization. Safety follow up data was collected by telephone contact every 3 months after the EOS visit.

Antroquinonol (Hocena)

Fresh or archival biopsy tissue to determine KRAS is not mutant. Patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression.

K-Ras Negative

Fresh or archival biopsy tissue to determine KRAS is mutant. Patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression.

K- Ras Mutant

Total

Age, Categorical

Sex: Female, Male

Asian

Black or African American

White

Race/Ethnicity, Customized

United States

Taiwan

Region of Enrollment

Fully active

Restricted in physically strenuous activity

Capable of all selfcare more than 50% work

ECOG performance status

Howard Cheng

200mg TID for treating KRAS negative patients 12 weeks

Progression-free Survival Rate/KRAS Negative Group

Progression-free Survival Rate/KRAS Mutant Group

Defined as the proportion of patients alive and progression free at Week 12.

Progression Free Survival Rate

Antroquinonol Day 28

There were 22 patients with reported concentration data who were eligible for the PK population.

Cmax

Patient without any chemotherapy before join Study

Non- Prior Chemotherapies

Patient join with One line failed prior chemotherapies

One Line Failed Prior Chemotherapies

Patients join with two lines failed prior chemotherapies

Two Lines Failed Prior Chemotherapies

patient failed more than two line chemotherapies before join.

More Than Two Lines Failed Prior Chemotherapies

Disease Control Rate (DCR)

T½: the Time Required for a Quantity to Reduce to Half Its Initial Value

patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression, unacceptable toxicity, non compliance or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever comes first.

Antroquinonol: patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression, unacceptable toxicity, non compliance or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever comes first.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Determine Function of Antroquinonol in Combination With SOC in First Line Metastatic Pancreatic Cancer	NCT03310632	Pancreatic Neop...	Antroquinonol	18 Years -	Golden Biotechnology Corporation
Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC	NCT02047344	Non-small Cell ...	Antroquinonol	18 Years -	Golden Biotechnology Corporation
Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC	NCT02047344	Non-small Cell ...	Antroquinonol	18 Years -	Golden Biotechnology Corporation

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