An Oxaliplatin-Based Phase II Randomized Study of Induction Chemotherapy Followed by Preoperative Chemoradiotherapy or Preoperative Chemoradiotherapy in Patients With Resectable Esophageal or Gastroesophageal Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- Pathologic Complete Response Rate
研究概览
简要总结
The goal of this clinical research study is to learn if a combination of the investigational drug oxaliplatin with 5-Fluorouracil (5-FU) (given at the same time as radiation therapy) is as effective as a combination of these two drugs given before and during radiation therapy in the treatment of esophageal or gastroesophageal cancers. The safety of these combinations of therapy will also be compared.
Objectives:
Primary objective:
Compare the Pathologic Complete Response rate and % of patients with <50% residual cancer in the resected surgical specimen between Arms A and B.
Secondary objectives:
- Compare 1-year and 3-year survival rates, median survival time, R0 resection rates, safety, and local plus systemic relapse rates between Arms A and B
- Perform exploratory correlative studies on blood, adjacent normal and cancer tissue to assess predictive markers of response and outcome.
- Evaluate the joint effects, including possible interactive effects, of proton-versus-photon therapy and treatment arm on overall survival, R0 resection rates, safety, and local plus systemic relapse rates.
详细描述
Oxaliplatin and 5-FU are chemotherapy drugs that are commonly used to treat certain kinds of cancers. 5-FU is designed to prevent cells from making DNA that is necessary for cell growth. This disrupts the growth of the cancer cells, which causes the cancer cells to start to die. Oxaliplatin is designed to damage DNA that is already formed.
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two groups. Participants in the first group (Arm A) will receive chemotherapy with radiation treatment. Participants in the second group (Arm B) will receive chemotherapy first then chemotherapy with radiation treatment. The chemotherapy that will be used in this study includes 5-FU and oxaliplatin. Arm B is 8 weeks longer than Arm A. Your doctor will discuss with you whether you will receive proton or photon radiation. If you receive proton radiation, it will be given in a building that is about a 5 minute drive from the main MD Anderson radiation clinic.
All participants will have had a routine upper gastrointestinal tract endoscopy and biopsy with endoscopic ultrasound examination before receiving treatment on this study. However, once you start on this study, the upper gastrointestinal tract endoscopy will be repeated before the 2nd cycle of induction chemotherapy Arm B (if needed), before chemoradiation, and before surgery. This procedure involves examination of the esophagus, stomach, and duodenum by a flexible tube. Biopsies will be taken as necessary.
Arm A:
If you are assigned to Arm A, you will receive treatment with 5-FU over 24 hours for 5 days each week for 5 weeks. It will be given as an infusion into a vein using a portable pump. This will start on Day 1 (Monday) and will continue until Day 5 (Friday) of each radiotherapy week for 5 weeks. You will need to carry this pump with you for about 96 hours. The pump is about the size of a personal compact disc player. You will also receive oxaliplatin as an infusion into a vein over 2 hours on Day 1. This will be repeated on Days 8, 15, 22, and 29. During this time you will receive radiation therapy every weekday for 5 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Local regional carcinoma of the thoracic esophagus (squamous cell or adeno) or gastroesophageal junction.
- •Patients with T1N1, and T2-3 with any N (M1a only) will be eligible.
- •Normal liver (serum glutamic-pyruvic transaminase (SGPT) < 56µL, Total Bilirubin <1.5 mg/dL), kidney (Creatinine <1.75 mg/dL), and bone marrow functions (AGN >1,500µL, platelet count >100,000/µL).
- •Performance status 0 or
- •Signed informed consent by the investigator or their designee and patient.
- •Medically fit for surgery.
- •No Celiac (except for the GE junction cancers), supraclavicular, or paraaortic nodal enlargement unless biopsy negative.
- •None of the celiac nodes should be larger than 2 cm
- •Male or Female but both sexes must practice adequate contraception while on therapy
- •>/=18 years but less than 76 years
- •No known allergy to any of the study drugs.
- •No prior therapy for this cancer.
- •No significant cancer (defined as non-melanomatous skin cancers and treated cervical cancers) within the past 5 years
- •New York Heart Association (NYHA) I and II
排除标准
- •Patients with T1N0, T4, or M1b cancer will be excluded
- •Significant comorbid conditions (defined as uncontrolled diabetes, active angina or heart failure, uncontrolled hypertension, or active psychiatric condition that prevents consistent participation and compliance).
- •More than grade 1 neuropathy
- •Unable to comprehend the requirements of the study or comply with it.
研究组 & 干预措施
Arm A: Chemo with Radiation Treatment
For 5 weeks, Chemo of 5-FU 250 mg/m^2 intravenous (IV) over 24 hours for 5 days weekly with Oxaliplatin 40 mg/m^2 IV daily over 2 hours, and Radiation treatment every weekday; then surgery.
干预措施: 5-Fluorouracil (Drug)
Arm A: Chemo with Radiation Treatment
For 5 weeks, Chemo of 5-FU 250 mg/m^2 intravenous (IV) over 24 hours for 5 days weekly with Oxaliplatin 40 mg/m^2 IV daily over 2 hours, and Radiation treatment every weekday; then surgery.
干预措施: Oxaliplatin (Drug)
Arm A: Chemo with Radiation Treatment
For 5 weeks, Chemo of 5-FU 250 mg/m^2 intravenous (IV) over 24 hours for 5 days weekly with Oxaliplatin 40 mg/m^2 IV daily over 2 hours, and Radiation treatment every weekday; then surgery.
干预措施: Radiation Therapy (Radiation)
Arm A: Chemo with Radiation Treatment
For 5 weeks, Chemo of 5-FU 250 mg/m^2 intravenous (IV) over 24 hours for 5 days weekly with Oxaliplatin 40 mg/m^2 IV daily over 2 hours, and Radiation treatment every weekday; then surgery.
干预措施: Surgery (Procedure)
Arm B: Pre-Op Chemo + Chemo with Radiation Treatment
Pre-Operative Chemo 5-FU 2.2 mg/m^2 IV continuous infusion over 48 hours start on day 1 and 15, and Oxaliplatin 100 mg/m^2 IV on day 1 and 15; followed by Surgery + Chemo with Radiation Therapy (same as Arm A)
干预措施: 5-Fluorouracil (Drug)
Arm B: Pre-Op Chemo + Chemo with Radiation Treatment
Pre-Operative Chemo 5-FU 2.2 mg/m^2 IV continuous infusion over 48 hours start on day 1 and 15, and Oxaliplatin 100 mg/m^2 IV on day 1 and 15; followed by Surgery + Chemo with Radiation Therapy (same as Arm A)
干预措施: Oxaliplatin (Drug)
Arm B: Pre-Op Chemo + Chemo with Radiation Treatment
Pre-Operative Chemo 5-FU 2.2 mg/m^2 IV continuous infusion over 48 hours start on day 1 and 15, and Oxaliplatin 100 mg/m^2 IV on day 1 and 15; followed by Surgery + Chemo with Radiation Therapy (same as Arm A)
干预措施: Radiation Therapy (Radiation)
Arm B: Pre-Op Chemo + Chemo with Radiation Treatment
Pre-Operative Chemo 5-FU 2.2 mg/m^2 IV continuous infusion over 48 hours start on day 1 and 15, and Oxaliplatin 100 mg/m^2 IV on day 1 and 15; followed by Surgery + Chemo with Radiation Therapy (same as Arm A)
干预措施: Surgery (Procedure)
结局指标
主要结局
Pathologic Complete Response Rate
时间窗: Surgery post chemotherapy (approximately 10-11 weeks)
Pathologic Complete Response rate: percentage of participants with response reported as Pathologic complete response (pathCR) following surgery. Once surgery performed, response to therapy judged in surgical specimen with three possible categories reported: 1) Pathologic complete response (no residual cancer in the specimen); 2) \<50% of residual cells in the surgical specimen; or 3) \>50% of cells in the surgical specimen. Upon recovery from chemoradiation (Chemo), surgery follows approximately 5-6 weeks later with response assessment. Arm A schedule consists of 6 weeks of Chemo +XRT, followed by 5-6 weeks of rest, followed by surgery. Arm B schedule consist of 8 weeks of Chemo, followed by 6 weeks of Chemo +XRT, followed by 5-6 weeks of rest, followed by surgery. In particular, Arm B is 8 weeks longer than Arm A.
次要结局
未报告次要终点