A Phase II Study of Efficacy and Tolerability of GW572016 in Patients With Advanced Hepatocellular and Biliary Carcinomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Proportion of Patients Demonstrating Objective Response (PR+CR) as Defined by RECIST
研究概览
简要总结
Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well lapatinib ditosylate works in treating patients with unresectable liver or biliary tract cancer
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the objective response rate (complete response [CR] + partial response [PR]) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria in each group of patients.
SECONDARY OBJECTIVES:
I. To evaluate the progression free survival at 6 months. II. To evaluate the toxicity profile of this treatment in each group of patients.
III. To evaluate median overall survival, 6 and 12 months survival rates. IV. To assess target-epidermal growth factor receptor (EGFR)/EGFR-P protein expression and the genes that regulate the cell cycle and apoptosis, which are either downstream of or cross-talk with the EGFR signaling pathway, to explore their association with clinical outcome.
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
- •Histologically confirmed diagnosis of 1 of the following:
- •Hepatocellular carcinoma (hepatoma)
- •Child-Pugh classification score ≤ 7
- •Biliary tract carcinoma
- •Surgically unresectable disease
- •Measurable disease
- •At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
- •Fresh tissue or paraffin embedded tissue from tumor blocks available
- •No ampulla of Vater tumors
- •No known brain metastases
- •Performance status - ECOG 0-1
- •Performance status - Karnofsky 60-100%
- •More than 12 weeks
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 75,000/mm^3
- •Bilirubin ≤ 2 times upper limit of normal (ULN)
- •AST and ALT ≤ 3 times ULN
- •Albumin ≥ 2.5 mg/dL
- •INR ≤ 1.5 (for patients not receiving an anticoagulant)
- •Live metastases or stable chronic liver disease allowed
- •No current active hepatic or biliary disease except for Gilbert's syndrome or asymptomatic gallstone
- •Creatinine ≤ 2 mg/dL
- •Ejection fraction normal by echocardiogram or MUGA
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •Able to swallow and retain oral medication
- •No gastrointestinal (GI) tract disease resulting in an inability to take oral medication
- •No malabsorption syndrome
- •No requirement for IV alimentation
- •No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No significant traumatic injury within the past 3 weeks
- •No active or ongoing infection
- •No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib
- •No psychiatric illness or social situation that would preclude study compliance
- •No other uncontrolled illness
- •No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •More than 4 weeks since prior biologic therapy
- •More than 4 weeks since prior immunotherapy
- •See Radiotherapy
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- •No prior cumulative doxorubicin dose > 450 mg/m^2
- •At least 14 days since prior and no concurrent glucocorticoids (e.g., dexamethasone or equivalent [dose > 1.5 mg/day])
- •More than 4 weeks since prior radiotherapy
- •More than 12 weeks since prior radiotherapy with or without a fluoropyrimidine as a radiosensitizer (for patients with biliary carcinoma only)
- •No prior surgical procedure affecting absorption
- •More than 3 weeks since prior major surgery
- •Recovered from all prior therapy
- 另有 48 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral lapatinib ditosylate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: lapatinib ditosylate (Drug)
Arm I
Patients receive oral lapatinib ditosylate once daily 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)
结局指标
主要结局
Proportion of Patients Demonstrating Objective Response (PR+CR) as Defined by RECIST
时间窗: Up to 3 years
PR (Partial Response) definded as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. CR (Complete Response) is defined as the disappearance of all target lesions.
次要结局
- Progression-free Survival(up to 6 months)
- Toxicity Profile Assessed Using NCI CTCAE Version 3.0(Up to 3 years)
- Median Overall Survival(Up to 3 years)
- Overall Survival(up to 12.6 months)
- Target-EGFR/EGFR-P Protein Expression(Up to 3 years)
- Expression Profile and Mutations of Genes Critical for EGFR and ERBB2 Signaling Pathways(Up to 3 years)