Combined Phase I/II Study of Epirubicin (Pharmorubicin®), Carboplatin (Paraplatin®) and Capecitabine (Xeloda®) (ECC) in the Treatment of Unresectable Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Cancer With Pharmacogenetic Correlates
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- recommended phase II dose
研究概览
简要总结
Although declining in incidence, gastric/gastroesophageal cancer is still a commonly diagnosed malignancy in Canada. Patients who have undergone surgical resection for early disease have a high rate of local recurrence and distant spread. More than 50% of patients present with either locally advanced or metastatic disease. Patients with advanced disease have an extremely poor prognosis, with average survival times ranging from 3 - 9 months. Development of new therapeutic approaches for locally advanced or metastatic gastric/gastroesophageal cancer, is clearly needed.
Despite its proven efficacy, ECF (epirubicin, cisplatin, and infusional 5-fluorouracil [5-FU]) has not been widely adopted in North America and is likely due to the technical difficulties and inconvenience associated with infusional chemotherapy. This study will substitute the oral chemotherapy drug capecitabine for infusional 5-FU in addition to substituting intravenous cisplatin with carboplatin (ECC - epirubicin, carboplatin and capecitabine). It is hoped that these substitutions will not only reduce the typical ECF related adverse effects but also allow for a more convenient administration of outpatient chemotherapy. It is also hoped that the genetic correlates of this study may also identify specific populations that preferentially benefit from ECC treatment.
详细描述
Background Information:
Capecitabine is an orally administered systemic prodrug of 5'-deoxy-5-fluorouridine which is converted to 5-fluorouracil. Capecitabine is readily absorbed from the gastrointestinal tract and then hydrolyzed in the liver. Capecitabine has been studied in the treatment of gastric/gastroesophageal cancer in addition to a wide variety of other malignancies (e.g. GI, breast).
Objectives
Phase I:
Primary Objective:
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced cancer
- •Gastric or esophageal cancer
- •Adequate organ function and bone marrow reserve
- •In general, patients must be 18 years or older
- •Life expectancy of > 12 weeks
- •World Health Organization (WHO) performance status 0-2
- •Left ventricular ejection fraction (LVEF) by multiple gated acquisition (MUGA) > 50%
- •Adequate organ function: hematological (ANC > 1.5 x 10^9/L; platelets > 100 x 10^9/L); hepatic (bilirubin < 1.5 x upper limit of normal [ULN]; AST/ALT < 3 x ULN); renal (calculated creatinine clearance > 60 ml/min).
- •Negative pregnancy test for females with child-bearing potential
- •Prior radiotherapy allowed but must be delivered to < 25% of bone marrow; must be completed > 4 weeks before study entry; and patients must have recovered from all side effects of the radiotherapy. Radiation must not be delivered to the sole response indicator lesion, unless there is documented evidence of disease progression in that site after completion of radiation.
- •Patients must be able to reliably tolerate and comply with oral/feeding tube administered medications (patients are considered eligible if the investigator deems that there is no malabsorption syndrome and no gastrointestinal [GI] obstruction that would impair the delivery of orally administered chemotherapy).
- •If patient has had prior anthracycline, cumulative dose must be < 300mg/m2 of doxorubicin or its equivalent.
排除标准
- •Abnormal organ function or active infection
- •Patients currently enrolled in another clinical trial involving active cancer treatment.
- •Treatment with doxorubicin > 300mg/m2 or its equivalent.
- •Serious medical conditions including myocardial infarction within 6 months prior to entry; unstable angina; active cardiomyopathy; unstable ventricular arrhythmia; congestive heart failure; uncontrolled hypertension; uncontrolled psychotic disorders; serious active infections; uncontrolled diabetes or any other medical condition that might be aggravated by study treatment.
- •Pre-existing neuropathy > grade 1
- •History of seizures or patients receiving anti-epileptic prophylaxis
- •Active and or progressive brain or leptomeningeal metastasis
- •Pregnant or lactating women
- •Patients with evidence or recent history of drug or alcohol abuse
- •Prior treatment with capecitabine or infusional 5-FU
- •Known hypersensitivity to carboplatin
- •5-FU, anthracyclines or known dihydropyrimidine dehydrogenase (DPD) deficiency.
- •Patients that lack physical integrity of the gastrointestinal (GI) tract leading to intestinal obstruction.
- •Patients taking warfarin (Coumadin) or other coumarin derivatives.
- •Presence of any mentally incapacitating psychological condition.
结局指标
主要结局
recommended phase II dose
次要结局
- preliminary study of efficacy