A Phase II Study of Oxaliplatin, Capecitabine, Cetuximab and Radiation in Pre-Operative Therapy of Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 130
- 主要终点
- Pathologic Complete Response Rate
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This phase II trial is studying the side effects and how well giving oxaliplatin, capecitabine, and cetuximab together with radiation therapy followed by surgery works in treating patients with stage II or stage III rectal cancer.
详细描述
OBJECTIVES:
- To assess the pathologic complete response rate for the combination of oxaliplatin, capecitabine, and cetuximab alone and concurrently with external beam radiotherapy for patients with adenocarcinoma of the rectum, stages II and III with wild-type K-ras.
- To estimate the 3-year disease-free survival probability in this patient population when treated with this regimen.
- To assess the frequency and severity of toxicities associated with this regimen in these patients.
- To explore, preliminarily, the association between expression levels of genes involved in the DNA repair, EGFR (epidermal growth factor receptor), angiogenesis, and 5-FU pathway (i.e., k-ras, TS [Thymidylate Synthase], ERCC-1 [excision repair cross complementing-1), TP [Thymidine phosphorylase], DPD [Dihydropyrimidine dehydrogenase], EGFR, VEGF [vascular endothelial growth factor], and IL-8 [interleukin-8]) and pathologic complete response. (Due to advances in methodology, the translational medicine objectives are being reconsidered. Therefore, results for this objective are not reported)
- To explore, preliminarily, the intratumoral gene expression levels of these genes after completion of study treatment.(Due to advances in methodology, the translational medicine objectives are being reconsidered. Therefore, results for this objective are not reported)
- To obtain, preliminarily, data on genomic polymorphisms of these genes for correlation with clinical outcome and toxicity. (Due to advances in methodology, the translational medicine objectives are being reconsidered. Therefore, results for this objective are not reported)
OUTLINE: This is a multicenter study.
- Neoadjuvant therapy (course 1): Patients receive oxaliplatin IV over 2 hours once a week for 5 weeks, oral capecitabine twice daily 5 days a week for 5 weeks, and cetuximab IV over 1-2 hours once a week for 5 weeks.
- Neoadjuvant therapy with concurrent radiotherapy (course 2): Beginning two weeks later, patients receive oxaliplatin IV over 2 hours once a week in weeks 1, 2, 4, and 5. Patients also receive capecitabine and cetuximab as in course 1. Patients also undergo external beam radiotherapy 5 days a week for 5 weeks beginning in week 1.
Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo surgery 3-8 weeks after completion of chemoradiotherapy.
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 —（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
Chemo + Chemo and radiation + Surgery
Chemotherapy Cycle 1 (1 cycle is 35 days):
- Oxaliplatin, 50 mg/m^2, IV, Days 1,8,15,22,29
- Cetuximab, 400 mg/m^2, IV, Day 1
- Cetuximab, 250 mg/m^2, IV, Days 8,15,22,29
- Capecitabine, 1650 mg/m^2/day, PO, Monday-Friday (Day 1-35)
Chemotherapy+ Radiation Cycle 2:
- Oxaliplatin, 50 mg/m^2, IV, Days 50,57,71,78
- Cetuximab, 250 mg/m^2, IV, Days 50,57,64,71,78
- Capecitabine, 1650 mg/m^1, PO, Monday-Friday (Day 50-84)
- Radiation therapy: Planning target value 1: 4500 cGy (centigray) in 25 fractions; Planning target value 2 (stage T3 patients): Boost of 540 cGy in 3 fractions; Planning target value 2 (stage T4 patients): Boost of 900 cGy in 5 fractions.
Therapeutic Surgical procedure: Resection
干预措施: cetuximab (Biological)
Chemo + Chemo and radiation + Surgery
Chemotherapy Cycle 1 (1 cycle is 35 days):
- Oxaliplatin, 50 mg/m^2, IV, Days 1,8,15,22,29
- Cetuximab, 400 mg/m^2, IV, Day 1
- Cetuximab, 250 mg/m^2, IV, Days 8,15,22,29
- Capecitabine, 1650 mg/m^2/day, PO, Monday-Friday (Day 1-35)
Chemotherapy+ Radiation Cycle 2:
- Oxaliplatin, 50 mg/m^2, IV, Days 50,57,71,78
- Cetuximab, 250 mg/m^2, IV, Days 50,57,64,71,78
- Capecitabine, 1650 mg/m^1, PO, Monday-Friday (Day 50-84)
- Radiation therapy: Planning target value 1: 4500 cGy (centigray) in 25 fractions; Planning target value 2 (stage T3 patients): Boost of 540 cGy in 3 fractions; Planning target value 2 (stage T4 patients): Boost of 900 cGy in 5 fractions.
Therapeutic Surgical procedure: Resection
干预措施: capecitabine (Drug)
Chemo + Chemo and radiation + Surgery
Chemotherapy Cycle 1 (1 cycle is 35 days):
- Oxaliplatin, 50 mg/m^2, IV, Days 1,8,15,22,29
- Cetuximab, 400 mg/m^2, IV, Day 1
- Cetuximab, 250 mg/m^2, IV, Days 8,15,22,29
- Capecitabine, 1650 mg/m^2/day, PO, Monday-Friday (Day 1-35)
Chemotherapy+ Radiation Cycle 2:
- Oxaliplatin, 50 mg/m^2, IV, Days 50,57,71,78
- Cetuximab, 250 mg/m^2, IV, Days 50,57,64,71,78
- Capecitabine, 1650 mg/m^1, PO, Monday-Friday (Day 50-84)
- Radiation therapy: Planning target value 1: 4500 cGy (centigray) in 25 fractions; Planning target value 2 (stage T3 patients): Boost of 540 cGy in 3 fractions; Planning target value 2 (stage T4 patients): Boost of 900 cGy in 5 fractions.
Therapeutic Surgical procedure: Resection
干预措施: oxaliplatin (Drug)
Chemo + Chemo and radiation + Surgery
Chemotherapy Cycle 1 (1 cycle is 35 days):
- Oxaliplatin, 50 mg/m^2, IV, Days 1,8,15,22,29
- Cetuximab, 400 mg/m^2, IV, Day 1
- Cetuximab, 250 mg/m^2, IV, Days 8,15,22,29
- Capecitabine, 1650 mg/m^2/day, PO, Monday-Friday (Day 1-35)
Chemotherapy+ Radiation Cycle 2:
- Oxaliplatin, 50 mg/m^2, IV, Days 50,57,71,78
- Cetuximab, 250 mg/m^2, IV, Days 50,57,64,71,78
- Capecitabine, 1650 mg/m^1, PO, Monday-Friday (Day 50-84)
- Radiation therapy: Planning target value 1: 4500 cGy (centigray) in 25 fractions; Planning target value 2 (stage T3 patients): Boost of 540 cGy in 3 fractions; Planning target value 2 (stage T4 patients): Boost of 900 cGy in 5 fractions.
Therapeutic Surgical procedure: Resection
干预措施: therapeutic surgical procedure (Procedure)
Chemo + Chemo and radiation + Surgery
Chemotherapy Cycle 1 (1 cycle is 35 days):
- Oxaliplatin, 50 mg/m^2, IV, Days 1,8,15,22,29
- Cetuximab, 400 mg/m^2, IV, Day 1
- Cetuximab, 250 mg/m^2, IV, Days 8,15,22,29
- Capecitabine, 1650 mg/m^2/day, PO, Monday-Friday (Day 1-35)
Chemotherapy+ Radiation Cycle 2:
- Oxaliplatin, 50 mg/m^2, IV, Days 50,57,71,78
- Cetuximab, 250 mg/m^2, IV, Days 50,57,64,71,78
- Capecitabine, 1650 mg/m^1, PO, Monday-Friday (Day 50-84)
- Radiation therapy: Planning target value 1: 4500 cGy (centigray) in 25 fractions; Planning target value 2 (stage T3 patients): Boost of 540 cGy in 3 fractions; Planning target value 2 (stage T4 patients): Boost of 900 cGy in 5 fractions.
Therapeutic Surgical procedure: Resection
干预措施: radiation therapy (Radiation)
结局指标
主要结局
Pathologic Complete Response Rate
时间窗: 15-20 weeks from registration
Pathologic response is evaluated after the patient has had surgery, and is based on local pathology review of the resected surgical specimen, according to the following: a) Pathologic complete response (pCR): on review of the resected rectal specimen and accompanying lymph nodes, no cancer is recognized by the pathologist; b) Microscopic cancer: gross tumor is not seen by the pathologist but tumor remains in the microscopic analysis of any part of the entire specimen; c) no response: gross cancer is found on pathologic examination of the resected rectal cancer and draining lymph nodes.
次要结局
- Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to This Regimen.(Up to 4 years)
- 3-year Disease-free Survival(3 years)