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

NCT03310632 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GHPanc-1-001
• Study Type: interventional
• Target: 52
• Locations: 3 countries
• Sites: 9

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.

Conditions

Pancreatic Neoplasm

Keywords

Antroquinonol; Hocena; metastatic pancreatic cancer

Outcome Measures

Primary Outcomes (2)

• MTD( phase I)

  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

  4 weeks

• tumor assessment in millimeters

  measure tumor size by CT or MRI

  6 months

Secondary Outcomes (5)

• Body Surface Area in meter^2

  up to 48 weeks

• Maximum Plasma Concentration

  3 weeks

• Area Under the Curve

  3 weeks

• CA19-9 level in units per milli-liter

  up to 48 weeks

• Eastern Cooperative Oncology Group (ECOG) status

  up to 48 weeks

Study Arms (1)

Antroquinonol with SOC

EXPERIMENTAL

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.

Drug: Antroquinonol

Interventions

Antroquinonol DRUG

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.

Also known as: Hocena

Antroquinonol with SOC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients ≥18 years of age.
• Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas, measurable according to the RECIST 1.1.
• Diagnosed with metastatic disease within 6 weeks before enrollment.
• 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).
• 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.
• ECOG performance status of 0 or 1.
• For women of childbearing potential, a negative serum pregnancy test result at Screening.
• 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:

You may not qualify if:

• Islet-cell neoplasms or locally advanced disease.
• Chemo-, hormone-, or immunotherapy or investigational drug at Screening or prior to enrollment.
• 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.
• 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 \[test performed within the past 12 months prior to the date of first administration of study drug\]).
• Patients with any serious active infection (ie, requiring an IV antibiotic, antifungal, or antiviral agent).
• Patients with known human immunodeficiency virus, active hepatitis B, or active hepatitis C.
• 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.
• Known or suspected substance abuse or alcohol abuse.
• 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.
• 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.
• Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not employing an effective method of contraception.
• Any known hypersensitivity to any component of nab-paclitaxel, gemcitabine, or antroquinonol.

Sponsors & Collaborators

• Golden Biotechnology Corporation: lead
• Covance: collaborator

Study Sites (9)

Florida Hospital Tampa

Tampa, Florida, 33613, United States

Location

CTCA Southeastern Regional Medical Center

Newnan, Georgia, 30265, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Cancer Treatment Centers of America - Eastern Regional Medical Center

Philadelphia, Pennsylvania, 19124, United States

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Severance Hospital

Seoul, 3722, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

antroquinonol

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 1, 2017
• First Posted: October 16, 2017
• Study Start: December 1, 2017
• Primary Completion: November 1, 2023
• Study Completion: December 31, 2024
• Last Updated: September 25, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3); TW (2); US (4)