A Phase I/II Study of Taxotere, Oxaliplatin, and 5- Fluorouracil
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil (Phase I)
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as docetaxel, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of docetaxel when given with oxaliplatin and fluorouracil and to see how well they work in treating patients with metastatic or unresectable stomach cancer, gastroesophageal junction cancer, or other solid tumor.
详细描述
OBJECTIVES:
Primary
- To establish the maximum tolerated dose of docetaxel when administered with oxaliplatin and fluorouracil in patients with metastatic or unresectable solid tumors. (Phase I)
- To determine the response rate in patients with metastatic or unresectable adenocarcinoma of the stomach or gastroesophageal junction treated with this regimen. (Phase II)
Secondary
- To determine the dose limiting toxicity of this regimen in these patients.
- To evaluate the frequency of CYP3A4, CYP3A5, and MDR polymorphisms and their impact on toxicity of docetaxel.
- To evaluate the frequency of XRCC1 and ERCC2 polymorphisms and their impact on the toxicity of oxaliplatin.
- To evaluate the frequency of DPD and TSER polymorphisms and their impact on the toxicity of fluorouracil.
- To characterize the toxicity profile of this regimen in these patients.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1a
Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: docetaxel (Drug)
Cohort 1a
Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: fluorouracil (Drug)
Cohort 1a
Docetaxel 25 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: oxaliplatin (Drug)
Cohort 2a
Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: docetaxel (Drug)
Cohort 2a
Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: fluorouracil (Drug)
Cohort 2a
Docetaxel 30 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: oxaliplatin (Drug)
Cohort 3a
Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: docetaxel (Drug)
Cohort 3a
Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: fluorouracil (Drug)
Cohort 3a
Docetaxel 40 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: oxaliplatin (Drug)
Cohort 4a
Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: docetaxel (Drug)
Cohort 4a
Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: fluorouracil (Drug)
Cohort 4a
Docetaxel 50 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: oxaliplatin (Drug)
Cohort 5a
Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: docetaxel (Drug)
Cohort 5a
Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: fluorouracil (Drug)
Cohort 5a
Docetaxel 60 mg/m2 + oxaliplatin 85 mg/m2 + 5-Fluorouracil 2.4 gm/m2
干预措施: oxaliplatin (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil (Phase I)
时间窗: After completion of 1 cycle of therapy (1 cycle = 14 days)
The MTD will be determined using a 3+3 dose escalating design. There will be 5 dose cohorts: Cohort 1a 25mg/m2 Cohort 2a 30mg/m2 Cohort 3a 40 mg/m2 Cohort 4a 50 mg/m2 Cohort 5a 60 mg/m2 3 patients will be enrolled at dose of 25mg/m2 docetaxel. If no dose limiting toxicities (DLTs) are seen then dose will be escalated to next cohort and 3 patients will be treated at that dose level. If a DLT is seen at any dose, then 3 more patients will be enrolled at that dose level. If 1 patient out of 6, experience a DLT then MTD will be determined to be at this dose level. If 2 or more DLTs are seen in first 3 patients at that dose, then MTD will be one dose lower to the level where the DLTs were experienced. Dose of docetaxel will be escalated by use of cohorts until the MTD for phase II is determined. DLTs were defined using the National Cancer Institute Common Toxicity Criteria Version 3.0
Response Rate in Patients With Adenocarcinoma of the Stomach or Gastroesophageal Junction (Phase II)
时间窗: After 4 cycles of therapy (1 cycle = 14 days)
Overall Response Rate (ORR) is defined as Complete Response (CR) plus Partial Response (PR) and will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan. Complete Response (CR) - Disappearance of all target lesions. Partial Response (PR), \>=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum. Stable Disease, neither sufficient shrinkage to qualify for Partial disease nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD while on study. Progressive Disease - \<=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
次要结局
- Frequency of CYP3A4, CYP3A5, and MDR Polymorphisms and Their Impact on Docetaxel Toxicity(Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle)
- Toxicity Profile(Day 1 of each cycle of therapy with 1 cycle =14 days until disease progression for up to a maximum of 34 cycles and 30 days after last treatment)
- Dose-limiting Toxicity of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil(After 1 cycle of therapy (1 cycle = 14 days))
- Frequency of XRCC1 and ERCC2 Polymorphisms and Their Impact on Oxaliplatin Toxicity(Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle)
- Frequency of DPD and TSER Polymorphisms and Their Impact on Fluorouracil Toxicity(Blood sample cycle 1 day 1 and toxicity on day 1 of each cycle)