A Phase 2 Study of AZD6244 in Advanced or Metastatic Hepatocellular Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 6
- 主要终点
- Number of Participants With Radiographic Objective Response (OR)
研究概览
简要总结
This phase II trial is studying selumetinib to see how well it works in treating patients with locally advanced or metastatic liver cancer. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth.
详细描述
PRIMARY OBJECTIVES:
I. To ascertain the objective response rate (complete response and partial response) in patients with locally advanced or metastatic hepatocellular carcinoma treated with AZD6244 (selumetinib).
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of AZD6244 when administered to patients with hepatocellular carcinoma and mild (Child's A to compensated Child's B) liver dysfunction.
II. To describe the pharmacokinetics (PK) of AZD6244 in this patient population and compare in exploratory fashion to the established PK profile in patients with normal hepatic function.
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
- •Meets 1 of the following criteria:
- •Histologically or cytologically confirmed hepatocellular carcinoma
- •Serum alpha fetoprotein > 1000ng/dL with characteristic imaging findings coupled with the appropriate clinical scenario (i.e., chronic hepatitis and/or cirrhosis)
- •Child's A or B cirrhosis allowed
- •If Child's B cirrhosis is present, the patient may not have significant encephalopathy or ascites that requires paracentesis and must meet laboratory criteria (i.e., well-compensated Child's B)
- •Metastatic disease (including any proven lymph node metastases) or localized disease not amenable to potentially curative transplant/locoregional/surgical therapy as determined by a qualified surgeon or tumor board
- •Measurable disease, defined as at least one unidimensionally measurable ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- •No known brain metastases
- •ECOG performance status ≤ 2
- •Life expectancy > 3 months
- •Leukocytes ≥ 3,000/mm³
- •Absolute neutrophil count ≥ 1,500/mm³
- •Platelets ≥ 75,000/mm³
- •Total bilirubin < 2 times upper limit of normal (ULN)
- •AST/ALT < 5 times ULN
- •Creatinine < 1.5 mg/dL or creatinine clearance ≥ 60 mL/min
- •INR < 1.4
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception before, during, and for 4 weeks after completion of study treatment
- •Willing to undergo protocol-required tumor biopsies (patients must also be able to have any anticoagulation held for an appropriate period of time)
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD6244 or its excipient Captisol®
- •No refractory nausea and vomiting or chronic gastrointestinal diseases (e.g., inflammatory bowel disease) that would preclude adequate absorption
- •No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
- •No active illicit substance or alcohol abuse
- •Able to understand and willing to sign a written informed consent document
- •Recovered from prior therapy
- •At least 4 weeks since prior chemo embolization, radio embolization (90Y microspheres), resection, or radio frequency/cryoablation
- •Must have measurable disease outside the treated area or unequivocal evidence of disease progression within the treated area
- •More than 4 weeks since prior radio therapy or major surgery
- •No prior organ transplantation
- •No prior systemic chemotherapy
- •No prior sorafenib
- •No prior therapeutic antibody or experimental systemic therapy (oral or intravenous)
- •No prior hepatic artery infusion of chemotherapy
- •No prior mitogen-activated protein kinase inhibitor
- •No prior significant bowel resection that would preclude adequate absorption
- •No concurrent fruit or juice of the grapefruit during AZD6244 therapy
- •No concurrent anti retroviral therapy for HIV-positive patients
- •No other concurrent investigational or commercial agents or therapies for this cancer
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor therapy)
Patients receive a single dose of selumetinib on day 1 and undergo blood collection for PK sampling pre-dose (within 30 min of dosing), 15 and 30 minutes and 1, 2, 4, 8, 12, 24 and 48 hours post-dose. Beginning 48 hours after the initial dose and continuing until day 21, patients receive oral selumetinib twice daily. Patients also undergo blood collection for PK sampling on day 15 of course 1. In all subsequent courses, patients receive selumetinib on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: selumetinib (Drug)
Treatment (enzyme inhibitor therapy)
Patients receive a single dose of selumetinib on day 1 and undergo blood collection for PK sampling pre-dose (within 30 min of dosing), 15 and 30 minutes and 1, 2, 4, 8, 12, 24 and 48 hours post-dose. Beginning 48 hours after the initial dose and continuing until day 21, patients receive oral selumetinib twice daily. Patients also undergo blood collection for PK sampling on day 15 of course 1. In all subsequent courses, patients receive selumetinib on days 1-21. Treatment repeats every 21 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
Number of Participants With Radiographic Objective Response (OR)
时间窗: 33 weeks
To ascertain the objective response rate (Complete Response + Partial Response \[CR+PR\]) of patients with the single-agent AZD6244. Our study utilized Response Evaluation Criteria in Solid Tumors (RECIST) to evaluate response. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Median Progression Free Survival (PFS)(33 weeks)
- Median Overall Survival (OS)(33 weeks)