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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 14
- 主要终点
- MTD( phase I)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients ≥18 years of age.
- •Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas, measurable according to the RECIST 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
- •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:
- •Established use of oral, injected, or implanted hormonal methods of contraception
- •Placement of an intrauterine device or intrauterine system
- •Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
- •Male sterilization (with the appropriate postvasectomy documentation of the absence of sperm in the ejaculate)
- •True abstinence (when this is in line with the preferred and usual lifestyle of the patient).
- •Patient must be able to provide written informed consent for participation in the study.
- •Life expectancy ≥12 weeks as assessed by the Investigator.
排除标准
- •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.
研究组 & 干预措施
Cohort 1
200mg TID Antroquinonol combination with the standard of care (SOC) (nab-paclitaxel 125 mg/m^2 + gemcitabine 1,000 mg/m^2).
干预措施: Antroquinonol (Drug)
Expansion Cohort
300mg TID Antroquinonol combination with the standard of care (SOC) (nab-paclitaxel 125 mg/m^2 + gemcitabine 1,000 mg/m^2).
干预措施: Antroquinonol (Drug)
Cohort 2
300mg TID Antroquinonol combination with the standard of care (SOC) (nab-paclitaxel 125 mg/m^2 + gemcitabine 1,000 mg/m^2).
干预措施: Antroquinonol (Drug)
结局指标
主要结局
MTD( phase I)
时间窗: 4 weeks
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
tumor assessment in millimeters
时间窗: 6 months
measure tumor size by CT or MRI
次要结局
- Maximum Plasma Concentration(3 weeks)
- Body Surface Area in meter^2(up to 48 weeks)
- Eastern Cooperative Oncology Group (ECOG) status(up to 48 weeks)
- Area Under the Curve(3 weeks)
- CA19-9 level in units per milli-liter(up to 48 weeks)