An Open-labeled Study to Evaluate Efficacy of Combining Erbitux Plus Concurrent Chemo-radiotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- Number of Participants With Overall Response Rate (RR)
研究概览
简要总结
The purpose of this study is to determine whether the treatment of locally advanced esophageal squamous cell carcinoma (ESCC)with cetuximab in combination with paclitaxel, cisplatin and radiation improve clinical outcomes.
详细描述
Esophageal cancer is the sixth leading cause of cancer death worldwide.
Over the past 2 decades, well-designed clinical trials have documented the clinical benefits of combination of chemotherapy and radiation for localized esophageal cancer, either as primary therapy or in neoadjuvant setting.
Paclitaxel, a radiation sensitizer, has important single-agent activity in esophageal cancer. Paclitaxel-based chemoradiation has been the framework for the recent Radiation Therapy Oncology Group (RTOG) trials of nonoperative management of esophageal cancer.
Accumulating clinical evidence suggests that epidermal growth factor receptor (EGFR) represents a viable target in the treatment of esophageal cancer. EGFR expression is associated with poor prognosis. Cetuximab, a monoclonal antibody, binds specifically to EGFR on both normal and tumor cells and competitively inhibits the binding of EGF and other ligands, such as transforming growth factor (TGF)-α.
Preclinical models have suggested synergy between cetuximab, paclitaxel, cisplatin and radiation. For patients with locally advanced head and neck cancer, the combination of cetuximab and radiation has demonstrated both response and survival benefit.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inpatients or outpatients, ≥ 18 years of age
- •Histologically confirmed primary (non-recurrent) ESCC fulfilling one of the following criteria (AJCC Staging System)
- •cervical esophageal carcinoma, stage Ⅱ-Ⅲ
- •upper thoracic esophageal carcinoma, stage Ⅱ-Ⅲ, or mid-thoracic esophageal carcinoma, stage Ⅱ-Ⅲ,which is medically unfit for surgery, surgery been refused and patient medically able to tolerate chemo-radiation.
- •Evidence of unidimensional measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST).
- •ECOG Performance status of 0-1
- •Effective contraception for both male and female patients if the risk of conception exists
- •Adequate bone marrow reserves: neutrophil (ANC) count ≥ 1500 /mm^3, platelet count ≥ 100,000 /mm^3, hemoglobin ≥ 9 g/dl
- •Adequate renal function: serum creatinine ≤ 1.5 mg/dl and/or calculated creatinine clearance ≥ 60 ml/min
- •Adequate hepatic function: bilirubin level ≤ 1.5 x ULN, ASAT & ALST ≤ 1.5 x ULN
- •Tumor tissue available for KRAS biomarker test
- •Signed written informed consent prior to study entry
排除标准
- •Previous chest radiotherapy, systemic chemotherapy, and major esophageal surgery
- •Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol
- •Multiple primary carcinomas of the esophagus
- •Pregnancy (confirmed by serum or urine β-HCG) or lactation period;
- •Uncontrolled diabetes, hypertension, and severe cardiac or pulmonary disease
- •Unable to comprehend the study requirements or who are not likely to comply with the study parameters;
- •Distant metastasis
- •Second malignancy, except for curable non-melanoma skin cancer, cervical cancer in situ, or malignant disease, free for ≥ 5 years
- •Known grade 3 or 4 allergic reaction to any of the study treatment
研究组 & 干预措施
cetuximab, concurrent chemo-radiotherapy
Cetuximab, injection, loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) Paclitaxel, injection,45 mg/m^2 (Day 1, every week for Weeks 2-8) Cisplatin, injection,20 mg/m^2 (Day 1, every week for Weeks 2-8) radiation therapy, 59.4 Gy, 1.8 Gy/33 fractions,1 fraction daily, Days 1-5 every week for Weeks 2-7, and Days 1-3 for Week 8
干预措施: cetuximab (Erbitux) (Drug)
cetuximab, concurrent chemo-radiotherapy
Cetuximab, injection, loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) Paclitaxel, injection,45 mg/m^2 (Day 1, every week for Weeks 2-8) Cisplatin, injection,20 mg/m^2 (Day 1, every week for Weeks 2-8) radiation therapy, 59.4 Gy, 1.8 Gy/33 fractions,1 fraction daily, Days 1-5 every week for Weeks 2-7, and Days 1-3 for Week 8
干预措施: Paclitaxel (Drug)
cetuximab, concurrent chemo-radiotherapy
Cetuximab, injection, loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) Paclitaxel, injection,45 mg/m^2 (Day 1, every week for Weeks 2-8) Cisplatin, injection,20 mg/m^2 (Day 1, every week for Weeks 2-8) radiation therapy, 59.4 Gy, 1.8 Gy/33 fractions,1 fraction daily, Days 1-5 every week for Weeks 2-7, and Days 1-3 for Week 8
干预措施: Cisplatin (Drug)
cetuximab, concurrent chemo-radiotherapy
Cetuximab, injection, loading dose400 mg/m^2,(Day1 in Week1) followed by 250 mg/m^2(Day1, every week for Weeks 2-8) Paclitaxel, injection,45 mg/m^2 (Day 1, every week for Weeks 2-8) Cisplatin, injection,20 mg/m^2 (Day 1, every week for Weeks 2-8) radiation therapy, 59.4 Gy, 1.8 Gy/33 fractions,1 fraction daily, Days 1-5 every week for Weeks 2-7, and Days 1-3 for Week 8
干预措施: Radiation (Radiation)
结局指标
主要结局
Number of Participants With Overall Response Rate (RR)
时间窗: 1 to 3 month after therapy
The overall response rate was defined as the numbers of patients with a complete response (CR) or partial response (PR). CR was defined as no target lesion at follow-up computed tomography scan and barium swallow examination 3-6 weeks after completion of chemo-radiation. PR was defined at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Number of Participants With Toxicity(Every week during treatment and 1 month after therapy)
- Participants With Overall Survival (OS) at 1 Year(1 year from the date of diagnosis)
- Participants With Overall Survival (OS) at 3 Year(3 year from the date of diagnosis)
- Participants With Progression Free Survival (PFS)(Recurrence or metastasis from the date of diagnosis)
- Number of Participants With K-ras Gene Mutation(07/29/2010-09/30/2010)