A Phase I/II Study of S-1 and Oxaliplatin Based Definitive Concurrent Chemoradiotherapy (SOX-CRT-01) for Unresectable Locally Advanced Esophageal Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events
研究概览
简要总结
Patients with esophageal cancer that had locally advanced diseases or with unresectable diseases are being asked to participate in this phase I/II study.
This phase I/II study is being conducted to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and efficacy of IMRT combined with S-1 and Oxaliplatin (SOX) based chemotherapy for unresectable locally advanced esophageal cancer.
详细描述
Esophageal carcinoma (EC) remains difficult to cure with overall 5-year survival rates for locally advanced stages being poor. Definitive concurrent chemoradiotherapy (dCRT) remains the mainstay of treatment for locally advanced and unresectable EC. Oxaliplatin is a new generation platinum with a more preferable toxicity profile compared to cisplatin. Furthermore, S-1 combines 5-Fu prodrug (tegafur) and two modulators of 5-Fu metabolism, gimeracil (CDHP) and oteracil. Basic studies showed that S-1 has superior anti-cancer effects than 5-Fu and enhances the sensitivity of cancer cells to the effects of radiotherapy. Herein, we designed a prospective phase I/II study, which is combined S-1 and oxaliplatin with IMRT for the patients with locally advanced and unresectable esophageal cancer, and evaluated the tolerability and efficacy of this combination.
<Phase I>
Primary Objective:
To establish the safety of combination chemotherapy comprising oxaliplatin (escalating doses: 110, 120, 130 mg/m2, day 1 and day 29), fixed dose of S-1 (80 mg/m2, day1-14 and day 29-42) and IMRT (5040cGy/28fx/5W+) in unresectable locally advanced esophageal cancer.
Secondary Objective:
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
- •Cytopathological confirmed esophageal cancer with unresectable locally advanced diseases;
- •Age of 18-70;
- •ECOG performance status: 0-1;
- •No treatments prior to enrollment;
- •Patients must have measurable or evaluable disease with at least one tumor mass maximum diameter ≥10mm by multi-slice spiral CT or MR scan. Imaging exam must be performed within 15 days from enrollment.
- •Normal marrow function and the blood tests must be collected within 7 days from enrollment with a hemoglobin of ≥90g/L, an white blood cell (WBC) counts of ≥4.0×109/L，a neutrophil count of ≥2.0×109/L, , a platelet count of ≥100×109/L, a total bilirubin (TBil) of ≤1.0 upper normal limitation (UNL), a creatinine (Cr) of ≤ 1.0 UNL, alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL, Alkaline phosphatase (AKP) ≤5.0 UNL. Pulmonary function (FEV1 >1L), and no major electrocardiogram abnormalities.
- •Normal electrocardiogram results and no history of congestive heart failure;
- •Patients must be with good compliance and agree to accept follow-up of disease progression and adverse events;
- •Informed consent signed.
排除标准
- •Prior treatments of chemotherapy or irradiation;
- •Poor bone marrow, liver and kidney functions, which would make chemotherapy intolerable;
- •Contraindication for irradiation: complete obstruction of esophagus, deep esophageal ulcer, fistula to mediastinum, or haematemesis;
- •Participating in other clinical trials;
- •Pregnancy, breast feeding, or not adopting birth control;
- •Clinically significant and uncontrolled major medical conditions including but not limited to: active uncontrolled infection, symptomatic congestive heart failure, Unstable angina pectoris or cardiac arrhythmia, psychiatric illness/ social situation that would limit compliance with study requirements; any medical condition, which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities;
- •Weight loss of 20% or more of normal body weight within 3 months.
- •The subject has had another active malignancy within the past five years except for cervical cancer in site, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin;
研究组 & 干预措施
SOX-based Chemoradiotherapy
IMRT is delivered with a daily fraction of 1.8 Gy to a total dose of 50.4 Gy over 5 weeks. Concurrent Oxaliplatin (3 levels for phase I: 110mg/m², 120 mg/m² and 130 mg/m², d1) and fixed dose of S-1 (80mg/ m², d1-14) are administered concurrently with IMRT, every 4 weeks. The recommended dose of Oxaliplatin are then further evaluated in the Phase II setting.
干预措施: Oxaliplatin (Drug)
SOX-based Chemoradiotherapy
IMRT is delivered with a daily fraction of 1.8 Gy to a total dose of 50.4 Gy over 5 weeks. Concurrent Oxaliplatin (3 levels for phase I: 110mg/m², 120 mg/m² and 130 mg/m², d1) and fixed dose of S-1 (80mg/ m², d1-14) are administered concurrently with IMRT, every 4 weeks. The recommended dose of Oxaliplatin are then further evaluated in the Phase II setting.
干预措施: S-1 capsule (Drug)
SOX-based Chemoradiotherapy
IMRT is delivered with a daily fraction of 1.8 Gy to a total dose of 50.4 Gy over 5 weeks. Concurrent Oxaliplatin (3 levels for phase I: 110mg/m², 120 mg/m² and 130 mg/m², d1) and fixed dose of S-1 (80mg/ m², d1-14) are administered concurrently with IMRT, every 4 weeks. The recommended dose of Oxaliplatin are then further evaluated in the Phase II setting.
干预措施: Intensity modulated radiotherapy (IMRT) (Radiation)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events
时间窗: 1 month
Phase I: toxicities will be assessed based on the common toxicity criteria for adverse events version 4.0 (CTCAE v4.0).
Response rate
时间窗: 1 month
Phase II: Response rate will be done after 4 weeks following the last radiotherapy session as evaluated by RECIST 1.1.
次要结局
- Recommended dose of Oxaliplatin for phase II trial.(1 month)
- Number of Participants with Adverse Events (Phase II).(6 months)
- Progression-free survival time(0-2 years)
- Overall survival time(0-2 years)
研究者
Yongshi Jia
Head of Radiation Oncology
Zhejiang Provincial People's Hospital