A Phase III Study of Nimotuzumab Plus Concurrent Chemoradiotherapy in Loco-regional Esophageal Squamous Cell Carcinoma
- Conditions
- Prosthesis Survival
- Interventions
- Radiation: radiotherapyDrug: chemoradiotherapy PaclitaxelOther: placeboDrug: chemoradiotherapy Cisplatin
- Registration Number
- NCT02409186
- Lead Sponsor
- Shandong Cancer Hospital and Institute
- Brief Summary
Esophageal cancer is the sixth leading cause of cancer death in 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. Nimotuzumab binds specifically to EGFR on both normal and tumor cells and competitively inhibits the binding of Epidermal Growth Factor (EGF) and other ligands, such as Transforming Growth Factor-α (TGF-α). Preclinical models have suggested synergy between nimotuzumab, paclitaxel, cisplatin and radiation. For our phase II study in locally advanced esophageal squamous cell carcinoma (ESCC), the combination of cetuximab and chemoradiotherapy has demonstrated both response and survival benefits. Myara et al reported that nimotuzumab plus concurrent chemoradiation therapy (CCRT) was safe and provided statistically significant objective response (47.8%) and disease control rate (60.9%) in nonresectable ESCC. With all these, the investigators plan to study phase III trial.
- Detailed Description
The primary endpoint of this study is overall survival, and the primary hypothesis is the experimental arm will improve median survival time (MST) from 18.2 month to 28.5 month. Assuming bilateral ɑ = 0.05, statistical power of 80%.Each group requires a minimum of 59 cases. Consider the 20% loss factor.The total sample size is 200 cases.It is 100 cases in each group.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 200
- Signed written informed consent prior to study entry
- age：18-70 years
- Histopathology confirmed primary esophageal squamous cell carcinoma, meet one of the following criteria (AJCC Staging System，2009，Seventh Edition):Cervical esophageal carcinoma(stage II-III);upper thoracic esophageal cancer or chest esophageal cancer that is unsuitable or refuse surgery (stage II-III)
- The existence of measurable lesions (according to Response Evaluation Criteria in Solid Tumors 1.1)
- Eastern Cooperative Oncology Group（ECOG）Performance status of 0-1
- Possible semi-liquid diet
- If there is a risk of pregnancy, male and female subjects must be effective contraception during treatment
- Normal bone marrow reserve: neutrophil (ANC) count≥1500/mm3,platelet count≥100,000 /mm3, hemoglobin≥5.6mmol/L(9g/dL)
- Normal renal function: serum creatinine≤1.5mg/dl and/or calculated creatinine clearance≥ 60ml/min
- Normal hepatic function: bilirubin level≤1.5×ULN, alanine aminotransferase aspartate transaminase（ASAT）& ALST≤1.5×ULN
- Subjects tumor tissue available for the relevant biomarker detection
- Previous chest radiotherapy, systemic chemotherapy, and major esophageal surgery
- Concurrent chronic systemic immune therapy, targeted therapy, anti-vascular endothelial growth factor（VEGF）therapy or EGFR-pathway targeting therapy not indicated in this study protocol
- Multiple primary carcinomas of the esophagus
- Pregnancy (confirmed by urine β-HCG) or lactation period
- Uncontrolled diabetes, hypertension, and severe cardiac or pulmonary disease
- There are obvious esophageal ulcers, chest and back more than moderate pain, symptoms of esophageal perforation
- Unable to comprehend the study requirements or who are not likely to comply with the study requirements
- Patients with distant metastasis
- Patients with other malignant disease, except for curable non-melanoma skin cancer, cervical carcinoma in situ or malignant disease cure for≥5 years
- Known grade 3 or 4 allergic reaction to any of the study treatment
- Peripheral neuropathy > grade 1
- Participation in another clinical study within the past 30 days
- Significant disease which, in the investigator's opinion, would exclude the patient from the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo plus chemoradiotherapy radiotherapy placebo：400mg/w，d1, week 1-7 Paclitaxel：45 mg/m2, d1, week 1-7 Cisplatin：20 mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7 placebo plus chemoradiotherapy placebo placebo：400mg/w，d1, week 1-7 Paclitaxel：45 mg/m2, d1, week 1-7 Cisplatin：20 mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7 Nimotuzumab plus chemoradiotherapy chemoradiotherapy Paclitaxel Nimotuzumab：400mg/w，d1, week 1-7 Paclitaxel：45mg/m2, d1, week 1-7 Cisplatin：20mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7 Nimotuzumab plus chemoradiotherapy chemoradiotherapy Cisplatin Nimotuzumab：400mg/w，d1, week 1-7 Paclitaxel：45mg/m2, d1, week 1-7 Cisplatin：20mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7 placebo plus chemoradiotherapy chemoradiotherapy Paclitaxel placebo：400mg/w，d1, week 1-7 Paclitaxel：45 mg/m2, d1, week 1-7 Cisplatin：20 mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7 Nimotuzumab plus chemoradiotherapy radiotherapy Nimotuzumab：400mg/w，d1, week 1-7 Paclitaxel：45mg/m2, d1, week 1-7 Cisplatin：20mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7 placebo plus chemoradiotherapy chemoradiotherapy Cisplatin placebo：400mg/w，d1, week 1-7 Paclitaxel：45 mg/m2, d1, week 1-7 Cisplatin：20 mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7 Nimotuzumab plus chemoradiotherapy Nimotuzumab Nimotuzumab：400mg/w，d1, week 1-7 Paclitaxel：45mg/m2, d1, week 1-7 Cisplatin：20mg/m2, d1, week 1-7 Three dimensional conformal RT（3DCRT）/IntensityModulatedRadiationTherapy（IMRT）：1.8 Gy/f/day, T59.4 Gy/33f,week 1-7
- Primary Outcome Measures
Name Time Method Over Survival up to 5 years
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (14)
Affiliated Hospital of Zunyi Medical College
🇨🇳Zunyi, Guizhou, China
Affiliated Hospital of Jiangsu University
🇨🇳Zhenjiang, Jiangsu, China
Shandong Cancer Hospital and Institute
🇨🇳Jinan, Shandong, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, Jiangsu, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Fourth Hospital of Hebei Medical University Tumor
🇨🇳Shijiazhuang, Hebei, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
The First Hospital of Zhejiang Province
🇨🇳Hangzhou, Zhejiang, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Renji Hospital Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Cancer Hospital Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
The Guangxi Zhuang Autonomous Region Cancer Hospita
🇨🇳Nanning, Guangxi, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, Guangdong, China