A Phase I Open Label Study Investigating the Combination of KD018 and Sorafenib (Nexavar) in Patients With Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Recommended phase II dose, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
研究概览
简要总结
This phase I trial studies the side effects and best dose of Chinese herbal formulation PHY906 when given together with sorafenib tosylate in treating patients with advanced liver cancer. Biological therapies, such as Chinese herbal formulation PHY906, may interfere with the growth of tumor cells and slow the growth of tumors. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib tosylate may also stop the growth of liver cancer by blocking blood flow to the tumor. Giving Chinese herbal formulation PHY906 together with sorafenib tosylate may work better in treating advanced liver cancer.
详细描述
PRIMARY OBJECTIVES:
I. To characterize the safety and tolerability of KD018 (Chinese herbal formulation PHY906) in combination with daily sorafenib (sorafenib tosylate) and to determine the maximum tolerated dose (MTD) of the combination of KD018 plus sorafenib to bring forward into phase 2.
SECONDARY OBJECTIVES:
I. To describe the efficacy of the combination of KD018 plus sorafenib at the explored dose-levels in terms of best overall response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
II. To assess the safety and tolerability of the combination of KD018 plus sorafenib as measured by the rate and severity of adverse events (AEs).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Ability to take oral drugs
- •Diagnosis of advanced hepatocellular carcinoma (HCC) according to the American Association for the Study of Liver Diseases (AASLD) guidelines
- •HCC stage B or C according to the Barcelona Clinic Liver Cancer (BCLC)
- •Previous or current use of sorafenib allowed
- •Measurable disease according to RECIST, i.e. at least one measurable lesion; this lesion should not have been previously treated with local therapy; a treated lesion may be used where these lesions are the only lesions available for evaluation and have shown definite progression since their last local treatment; local therapy must have been completed at least four weeks prior to baseline evaluation
- •Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Cirrhotic status of current Child-Pugh class A and B with no encephalopathy and no ascites (ascites controlled by diuretics is also excluded in this study); Child-Pugh status should be calculated based on clinical findings and laboratory results during the screening period
- •For patients with positive HBV-deoxyribonucleic acid (DNA) and/or positive of hepatitis B surface antigen (HBsAg) results, they must be treated with anti-virals, as prophylaxis at least 1-2 weeks prior to receiving study drug, cycle 1, day 1
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- •Platelets >= 75000 x 10^6/L
- •Hemoglobin (Hgb) >= 9 g/dL
- •Alanine aminotransferase (ALT) =< 5 x upper limit of normal (ULN)
- •Serum creatinine =< 1.5 x ULN
- •Ability to understand and willingness to sign a written informed consent and to be able to follow the visit schedule
- •Life expectancy of approximately 6 months
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; should a woman become pregnant, or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- •All subjects must have the ability to understand and the willingness to sign a written informed consent
- •Previous or current use of sorafenib and previous use of tamoxifen is allowed as previous systemic therapy
排除标准
- •Patients currently receiving any anti-cancer therapy, except sorafenib, or who have received any local anti-cancer therapy =< 4 weeks prior to baseline computed tomography (CT)/magnetic resonance imaging (MRI) scan, prior to cycle 1 treatment
- •Active bleeding during the last 30 days prior to cycle 1 treatment including variceal bleeding (esophageal varices should be treated according to standard practice e.g. ligation/banding and procedure completed 30 days prior to cycle 1 treatment)
- •Patients with a known hypersensitivity to KD018 or known hypersensitivity to sorafenib or contraindications to sorafenib based on the local sorafenib label
- •Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
- •Any severe and/or uncontrolled medical conditions including:
- •Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to cycle 1 treatment, serious uncontrolled cardiac arrhythmia, uncontrolled hypertension
- •Previous transient ischemic attack (TIA), cerebral vascular accident (CVA), symptomatic posterior vitreous detachment (PVD) within last 6 months of cycle 1 treatment
- •Congenital long QT syndrome
- •Patients with active alcohol intake
- •Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy, in the opinion of the investigator, except chronic HBV or HCV
- •Impairment of gastrointestinal function or who have gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
- •Patients receiving chronic treatment with corticosteroids (except for intermittent topical or local injection or aldosterone) or another immunosuppressive agent
- •Patients treated with drugs known to be strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A (CYP3A) unless the drugs are medically necessary and no substitutes are available
- •Patients who have undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from surgery
- •Patients who have received an investigative drug or therapy within the last 30 days prior to cycle 1 treatment
- •Pregnant and/or breastfeeding women
研究组 & 干预措施
Treatment (Chinese herbal formulation PHY906 and sorafenib)
Patients receive Chinese herbal formulation PHY906 PO BID on days 1-4, 8-11, 15-18, 21-24 and sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Chinese herbal formulation PHY906 (Dietary Supplement)
Treatment (Chinese herbal formulation PHY906 and sorafenib)
Patients receive Chinese herbal formulation PHY906 PO BID on days 1-4, 8-11, 15-18, 21-24 and sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: sorafenib tosylate (Drug)
Treatment (Chinese herbal formulation PHY906 and sorafenib)
Patients receive Chinese herbal formulation PHY906 PO BID on days 1-4, 8-11, 15-18, 21-24 and sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (Chinese herbal formulation PHY906 and sorafenib)
Patients receive Chinese herbal formulation PHY906 PO BID on days 1-4, 8-11, 15-18, 21-24 and sorafenib tosylate PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Recommended phase II dose, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4
时间窗: 28 days
次要结局
- Dose adjustment rate(Up to 6 years)
- Tumor response in terms of best overall response, assessed using RECIST(Up to 6 years)
- Serious adverse events as determined by NCI CTCAE version 4(Up to 4 weeks after completion of study treatment)
- Adverse events as determined by NCI CTCAE version 4(Up to 4 weeks after completion of study treatment)
- Sorafenib tosylate concentration after co-administration with Chinese herbal formulation PHY906(Baseline; 1 hour post-dose; 2 hours post-dose)
- Discontinuation rate(Up to 6 years)