Clinical Trials /

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

NCT03310632

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Determine Function of Antroquinonol in Combination With SOC in First Line Metastatic Pancreatic Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: GHPanc-1-001
  • NCT ID: NCT03310632

Conditions

  • Pancreatic Neoplasm

Interventions

DrugSynonymsArms
AntroquinonolHocenaAntroquinonol with SOC

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Antroquinonol with SOCExperimentalAntroquinonol 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

Eligibility Criteria

        Inclusion Criteria:

          1. Male and female patients ≥18 years of age.

          2. Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas,
             measurable according to the RECIST 1.1.

          3. Diagnosed with metastatic disease within 6 weeks before enrollment.

          4. Treatment-naïve patients with metastatic pancreatic adenocarcinoma who have received
             no previous systemic therapy (except adjuvant or neoadjuvant therapy if progression
             occurred >6 months from last treatment or surgery, respectively, and no prior
             nab-paclitaxel).

          5. Adequate hematologic, hepatic, and renal function, including:

               -  Hemoglobin ≥9 g/dL

               -  Absolute neutrophil count ≥1500/mm3

               -  Platelet count ≥100 000/mm3

               -  Total bilirubin ≤1.25 × upper limit of normal (ULN)

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN;
                  for patients with hepatic metastases, ALT and AST ≤5 × ULN

               -  Albumin ≥3 mg/dL

               -  Serum creatinine ≤1.5 mg/dL or calculated creatinine clearance ≥50 mL/min as
                  determined by the Cockcroft-Gault equation.

          6. ECOG performance status of 0 or 1.

          7. For women of childbearing potential, a negative serum pregnancy test result at
             Screening.

          8. Willing to use 2 medically accepted and effective methods of contraception from the
             list below during the study (both men and women as appropriate) and for 3 months after
             the last dose of study drug:

               1. Established use of oral, injected, or implanted hormonal methods of contraception

               2. Placement of an intrauterine device or intrauterine system

               3. Barrier methods of contraception: condom or occlusive cap (diaphragm or
                  cervical/vault caps) with spermicidal foam/gel/film/cream/suppository

               4. Male sterilization (with the appropriate postvasectomy documentation of the
                  absence of sperm in the ejaculate)

               5. True abstinence (when this is in line with the preferred and usual lifestyle of
                  the patient).

          9. Patient must be able to provide written informed consent for participation in the
             study.

         10. Life expectancy ≥12 weeks as assessed by the Investigator.

        Exclusion Criteria:

          1. Islet-cell neoplasms or locally advanced disease.

          2. Chemo-, hormone-, or immunotherapy or investigational drug at Screening or prior to
             enrollment.

          3. Treatment with any drug(s) known to be a strong inhibitor or inducer of
             CYP2C19,CYP3A4, CYP2C8, and CYP2E1 within 14 days of the date of first administration
             of study drug and during study treatment.

          4. Other malignancies diagnosed within the past 5 years (other than curatively treated
             cervical cancer in situ, nonmelanoma skin cancer, superficial bladder tumors Ta
             [noninvasive tumor] and TIS [carcinoma in situ], or nonmetastatic prostate cancer
             Stage 1 to 2, which has been previously treated with surgery or radiation therapy, and
             serum prostate-specific antigen is within normal limits [test performed within the
             past 12 months prior to the date of first administration of study drug]).

          5. Patients with any serious active infection (ie, requiring an IV antibiotic,
             antifungal, or antiviral agent).

          6. Patients with known human immunodeficiency virus, active hepatitis B, or active
             hepatitis C.

          7. Patients who have any other life-threatening illness or organ system dysfunction,
             which in the opinion of the Investigator, would either compromise patient safety or
             interfere with the evaluation of the safety of the study drug.

          8. Known or suspected substance abuse or alcohol abuse.

          9. Uncontrolled intercurrent illness, including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
             angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric
             illness/social situations that would limit compliance with study requirement,
             substantially increase risk of incurring AEs from study treatment, or compromise the
             ability of the patient to give written informed consent.

         10. Inability to swallow oral medications or a recent acute gastrointestinal disorder with
             diarrhea, (eg, Crohn's disease), malabsorption, or CTCAE Grade >2 diarrhea of any
             etiology at baseline.

         11. Female patients who are pregnant or breastfeeding, or male or female patients of
             reproductive potential who are not employing an effective method of contraception.

         12. Any known hypersensitivity to any component of nab-paclitaxel, gemcitabine, or
             antroquinonol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MTD
Time Frame:4 weeks
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:tumor assessment in millimeters
Time Frame:up to 48 weeks
Safety Issue:
Description:measure tumor size by CT or MRI
Measure:Body Surface Area in meter^2
Time Frame:up to 48 weeks
Safety Issue:
Description:measure patient's weight and height and calculated by {[Height (cm) × Adjusted Body Weight] × 1/3,600}^1/2
Measure:Maximum Plasma Concentration
Time Frame:3 weeks
Safety Issue:
Description:maximum observed plasma concentration of antroquinonol and paclitaxel
Measure:Area Under the Curve
Time Frame:3 weeks
Safety Issue:
Description:Plasma concentrations of antroquinonol and paclitaxel will be measured and PK parameters calculated where applicable.
Measure:CA19-9 level in units per milli-liter
Time Frame:up to 48 weeks
Safety Issue:
Description:blood will be draw and measured. Other emerging antroquinonol biomarkers may be evaluated.
Measure:Eastern Cooperative Oncology Group (ECOG) status
Time Frame:up to 48 weeks
Safety Issue:
Description:Medical Doctors judged the patient's performance status

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Golden Biotechnology Corporation

Trial Keywords

  • Antroquinonol
  • Hocena
  • metastatic pancreatic cancer

Last Updated

July 20, 2020