Phase II Study in Operable Adenocarcinoma of the Esophagus to Measure Response Rate and Toxicity of Preoperative Combined Modality Paclitaxel (Taxol®, Bristol-Myers Squibb), Cisplatin (Platinol®, Abbott Laboratories), ZD1839 (IRESSA®) and Radiotherapy Followed by Postoperative ZD1839
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Pathologic Complete Response Rate to the Neoadjuvant Regimen
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving gefitinib after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well giving paclitaxel, cisplatin, gefitinib, and radiation therapy followed by surgery and gefitinib works in treating patients with locally advanced cancer of the esophagus or gastroesophageal junction that can be removed by surgery.
详细描述
OBJECTIVES:
Primary
- Determine the pathologic complete response rate in patients with resectable, locally advanced adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant paclitaxel, cisplatin, gefitinib, and radiotherapy followed by surgery and adjuvant gefitinib.
Secondary
- Determine the survival of patients treated with this regimen.
- Determine the safety and tolerability of this regimen in these patients.
- Determine time to disease progression in patients treated with this regimen.
- Determine the plasma pharmacokinetics of unbound gefitinib in these patients.
- Conduct exploratory studies to determine if EGFR pathway component expression and activation correlates with response to therapy and survival of these patients.
- Determine if treatment with gefitinib alters the EGFR pathway in these patients.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenocarcinoma of the esophagus or gastroesophageal junction meeting the following criteria:
- •Newly diagnosed disease
- •Surgically resectable tumor
- •Primary esophageal tumor < 20 cm below the incisors
- •Tumor extending ≤ 2 cm into the cardia
- •Stage T2-3, N0-1, M0-1a tumor, as determined by imaging studies and biopsy
- •Documentation by endoscopic ultrasound, endoscopy, and CT scan of the chest and abdomen required
- •Any lesion suspicious for metastasis must be biopsied
- •M1a disease (i.e., celiac nodal metastasis) is allowed if other eligibility criteria are met
- •T4 disease (i.e., involvement of the pleura, pericardium, or diaphragm) allowed provided it is considered resectable
- •No CNS metastasis
- •ECOG performance status 0-1
- •Granulocyte count > 1,000/mm³
- •Platelet count > 75,000/mm³
- •Creatinine clearance > 60 mL/min
- •Total bilirubin < 1.5 mg/dL
- •No concurrent illness likely to preclude protocol therapy or surgical resection
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after completion of study therapy Exclusion Criteria
- •Known severe hypersensitivity to gefitinib or any of its excipients
- •Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
- •Evidence of other significant clinical disorder or laboratory finding that would preclude study participation
- •Evidence of clinically active interstitial lung disease
- •Chronic, stable radiographic changes that are asymptomatic are eligible
- •Prior or concurrent malignancy except basal cell or squamous cell skin cancer, cervical cancer, or any other curatively treated malignancy from which the patient has been disease-free and has a survival prognosis of > 5 years
- •Preexisting peripheral neuropathy > grade 1
- •Incomplete healing from prior oncologic or other major surgery
- •Prior chemotherapy, radiotherapy, or surgery for this cancer
- •More than 30 days since prior nonapproved or investigational drugs
- •Concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or Hypericum perforatum (St. John's wort)
- •Concurrent oral retinoids
排除标准
- 未提供
研究组 & 干预措施
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
干预措施: cisplatin (Drug)
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
干预措施: gefitinib (Drug)
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
干预措施: paclitaxel (Drug)
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
干预措施: adjuvant therapy (Procedure)
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy
Paclitaxel, Cisplatin, ZD1839 and Radiotherapy Followed by Postoperative ZD1839
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Pathologic Complete Response Rate to the Neoadjuvant Regimen
时间窗: 5 years
Study closed due to early stopping rule. Patient data was not analyzed. No additional information is available to report
次要结局
- Safety and Tolerability of This Regimen(5 years)
- Time to Progression(5 years)
- Correlation Between EGFR Pathway Component Expression and Activation With Pathologic Complete Response and Survival(5 years)
- Toxicity as Assessed by NCI CTC v2.0(5 years)
- Survival(5 years)