An Exploratory, Phase II Trial to Determine the Association of Lapatinib Induced Fluoropyrimidine Gene Changes With Efficacy Parameters of Lapatinib and Capecitabine in First Line Gastric Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 23
- 主要终点
- Change From Start of Run-in Period in Biomarker Expression Levels at Day 0
研究概览
简要总结
The study will determine if changes in expression of markers involved in the 5-FU pathways are associated with response to treatment with the combination of lapatinib and capecitabine independent of tumor erbB2 status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Has signed inform consent
- •Untreated, newly diagnosed, advanced metastatic or unresectable gastric cancer, including the gastro-esophageal junction
- •Tumor accessible to and patient consent for endoscopic biopsy at study start and after 7 days of single agent Lapatinib
- •Measurable disease according to RECIST criteria
- •Male or female > or = 18 years of age
- •Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram
- •must have adequate organ function as defined by baseline laboratory values
排除标准
- •Gastric carcinoid, sarcomas, or squamous cell cancer
- •Pregnant or lactating females
- •Intractable nausea, vomiting, or gastro intestinal obstruction requiring decompression and drainage with a gastric tube or nasogastric suction.
- •patients who require continuous enteral feeding
- •Malabsorption syndrome or uncontrolled inflammatory GI disease (Crohn's or ulcerative colitis
- •Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure
结局指标
主要结局
Change From Start of Run-in Period in Biomarker Expression Levels at Day 0
时间窗: evaluated at baseline and after 7 days of study treatment
Participants were analyzed for intratumoral expression levels of genes involved in the 5-fluorouracil (FU) pathway and lapatinib-targeted genes. Change in biomarker expression levels was calculated as the levels measured after the lapatinib Run-in Period (Baseline) of the study minus the levels measured at the start of monotherapy (Day -7). EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor. Data are presented as ratios of the normalized gene expression of the target gene to that of beta actin.
Percentage of Participants (Par.) With 5-month Progression-free Survival (PFS)
时间窗: From initial treatment up to 24 weeks (next available assessment after the 5-month assessment for progressive disease)
5-month (mo.) PFS was defined as the percentage of par. who were alive/progression free for 5 months from the time of initial treatment. PFS is defined as the time from the initial treatment until the first observation of disease progression (DP)/death due to any cause; the percentage of par. whose follow-up ended or was ongoing was reported. DP is defined as symptomatic progression or the appearance of \>=1 NL and/or unequivocal progression of existing non-TLs, and a \>=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since treatment started.
Response Rate (Measured as the Percentage of Participants With Response [Complete Response or Partial Response])
时间窗: From Baseline (Day 0) until disease progression or death due to any cause evaluated every 6 or 12 weeks (up to approximately 85 weeks)
Response is defined as documented evidence of complete response (CR) or partial response (PR). The investigator evaluated response based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response is defined as the disappearance of all target lesions (TLs) and non-TLs and the appearance of no new lesions (NLs). Partial response for TLs is defined as \>= a 30% decrease in the sum of the longest diameter (LD) of TLs, taking as a reference the Baseline sum LD. For non-TLs it is defined as the persistence of 1 or more non-TL and no new TLs or non-TLs.
次要结局
- PFS(From Baseline (Day 0) until disease progression or death due to any cause (up to approximately 85 weeks))
- Overall Survival (OS)(From Baseline (Day 0) until death due to any cause evaluated at approximately 12 months (up to approximately 100 weeks))
- Time to Progression (All Deaths Are Treated as Competing Risk)(From Baseline (Day 0) until disease progression or death due to any cause (up to approximately 85 weeks))
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Total Neutrophils at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Platelet Count at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for White Blood Cell (WBC) Count at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Time to Progression (All Deaths Due to Non-PD Are Treated as Competing Risk)(From Baseline (Day 0) until disease progression or death due to any cause (up to approximately 85 weeks))
- Time to Response(Baseline (Day 0) until first documented evidence of response (up to approximately 60 weeks))
- Duration of Response(From date of first documented evidence of response until the date of first documented sign of disease progression or death due to any cause (up to approximately 78 weeks))
- Number of Participants in the Indicated Categories for Best Overall Response (BOR)(From Baseline (Day 0) until disease progression or death due to any cause (up to approximately 85 weeks))
- Number of Participants With Change From Baseline (Measured as Any Grade Increase [AGI], Increase to Grade 3 [ItoG3], and Increase to Grade 4 [ItoG4]) in Toxicity Grades for Albumin at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Alkaline Phosphatase (ALP) at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Aspartate Aminotransferase (AST) at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4 ) in Toxicity Grades for Alanine Aminotransferase (ALT) at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Total Bilirubin at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Calcium at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Creatinine at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Glucose at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Potassium at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Magnesium at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Sodium at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Hemoglobin at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)
- Number of Participants With Change From Baseline (Measured as AGI, ItoG3, and ItoG4) in Toxicity Grades for Lymphocytes at the Indicated Time Points(Baseline (Day 0); Weeks 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, and 84; withdrawal (WD)/study conclusion (up to approximately 87 weeks); and worst-case on-therapy)