Clinical trial NCT02409186: A Phase III Study of Nimotuzumab Plus Concurrent Chemoradiotherapy in Loco-regional Esophageal Squamous Cell Carcinoma
Official title: A Randomized, Controlled, Double-blind Study to Evaluate Efficacy and Survival of Combining Nimotuzumab Plus Concurrent Chemo-radiotherapy in Loco-regional Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Prosthesis Survival
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
First posted: 2015-04-06
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Signed written informed consent prior to study entry
2. age：18-70 years
3. 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)
4. The existence of measurable lesions (according to Response Evaluation Criteria in Solid Tumors 1.1)
5. Eastern Cooperative Oncology Group（ECOG）Performance status of 0-1
6. Possible semi-liquid diet
7. If there is a risk of pregnancy, male and female subjects must be effective contraception during treatment
8. Normal bone marrow reserve: neutrophil (ANC) count≥1500/mm3,platelet count≥100,000 /mm3, hemoglobin≥5.6mmol/L(9g/dL)
9. Normal renal function: serum creatinine≤1.5mg/dl and/or calculated creatinine clearance≥ 60ml/min
10. Normal hepatic function: bilirubin level≤1.5×ULN, alanine aminotransferase aspartate transaminase（ASAT）\& ALST≤1.5×ULN
11. Subjects tumor tissue available for the relevant biomarker detection

Exclusion Criteria:

1. Previous chest radiotherapy, systemic chemotherapy, and major esophageal surgery
2. 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
3. Multiple primary carcinomas of the esophagus
4. Pregnancy (confirmed by urine β-HCG) or lactation period
5. Uncontrolled diabetes, hypertension, and severe cardiac or pulmonary disease
6. There are obvious esophageal ulcers, chest and back more than moderate pain, symptoms of esophageal perforation
7. Unable to comprehend the study requirements or who are not likely to comply with the study requirements
8. Patients with distant metastasis
9. Patients with other malignant disease, except for curable non-melanoma skin cancer, cervical carcinoma in situ or malignant disease cure for≥5 years
10. Known grade 3 or 4 allergic reaction to any of the study treatment
11. Peripheral neuropathy \> grade 1
12. Participation in another clinical study within the past 30 days
13. Significant disease which, in the investigator's opinion, would exclude the patient from the study

Primary outcomes:
measure: Over Survival
timeFrame: up to 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
state: Guangdong
city: Nanning
country: China
facility: The Guangxi Zhuang Autonomous Region Cancer Hospita
state: Guangxi
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical College
state: Guizhou
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University Tumor
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Zhenjiang
country: China
facility: Affiliated Hospital of Jiangsu University
state: Jiangsu
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital and Institute
state: Shandong
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Hangzhou
country: China
facility: The First Hospital of Zhejiang Province
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Shandong Cancer Hospital and Institute
name: Jinming Yu, Ph.D, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Shandong Cancer Hospital and Institute
name: Xue Meng, Ph.D, M.D
role: STUDY_DIRECTOR
References: