Clinical trial NCT02272699: Neoadjuvant Treatment of Nimotuzumab With Chemotherapy or Radiotherapy in Resectable Esophageal Squamous Cell Carcinoma
Official title: Neoadjuvant Treatment of Nimotuzumab With Chemotherapy or Radiotherapy Versus Surgery Alone in Resectable Esophageal Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
PHASE3
Conditions: Esophageal Squamous Cell Carcinoma
Keywords: Esophageal Squamous Cell Carcinoma
Nimotuzumab
Neoadjuvant treatment
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2014-10-23
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Esophageal cancer is one of common malignant tumors in China and esophageal squamous cell carcinoma (ESCC) is the dominant pathological type, accounting for more than 95% of all cases. One of our phase Ⅱ study introduced a combination treatment of an anti epithelial growth factor receptor (EGFR) agent, nimotuzumab, with paclitaxel and cisplatin as first-line treatment in unresectable or metastatic ESCC. The results showed that the overall response rate was 51.8% (29/56) and disease control rate was 92.9% (52/56). As a median follow-up of 24 months, the median progression-free survival for patients with metastatic disease and local advanced disease were 8.2 months and more than 23 months respectively. The overall survival for patients with metastatic disease was 13.9 months. It implied that as first-line chemotherapy, an addition of nimotuzumab to chemotherapy was a more active treatment option compared to other regimens published in previous studies. Investigations by Liang, J. and Ling, Y. also suggested that nimotuzumab in combining with radiotherapy or chemotherapy also showed anti-tumor activities and limited toxicities.

Therefore, we initiated this phase Ⅱ to Ⅲ clinical trial in which combining neoadjuvant treatments of nimotuzumab with chemotherapy or nimotuzumab with radiotherapy are compared with surgery alone for resectable stage Ⅱa to Ⅲ middle and lower thoracic esophageal squamous cell carcinoma patients. We hope to explore if these neoadjuvant combination treatments could bring survival benefit for ESCC patients.


Eligibility criteria: Inclusion Criteria:

* Patients must give written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors.
* Weight loss must be less than 10% in last 6 months.
* With an expected life expectancy of ≥ 12 months
* With a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale
* Patients must have histologically confirmed esophageal squamous cell carcinoma without prior treatments including surgery, chemotherapy, radiotherapy, and targeting treatment.
* With resectable disease of primary tumor in middle or lower thoracic esophagus and clinical stage Ⅱa-Ⅲ.
* With measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
* Without serious system dysfunction and could tolerate chemotherapy or radiotherapy.
* Patients must have normal marrow function with a hemoglobin (HGB) 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 ≤1.5 upper normal limitation (UNL), a creatinine (Cr) of ≤ 1.5 UNL, alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL.
* Patients must have normal electrocardiogram results and no history of congestive heart failure.
* Women of childbearing age should voluntarily take contraceptive measures.
* Without drug addition
* Patients must be with good compliance and agree to accept follow-up of disease progression and adverse events.

Exclusion Criteria:

* Allergic to known drug
* Patients who have received prior treatment including chemotherapy, radiotherapy and surgery.
* With unresectable disease including any T4b or M1 disease.
* Without measurable or evaluable disease.
* With history of other tumors except for those of cervical carcinoma in situ or skin basal cell carcinoma who had been completely treated and without relapse in last 5 years.
* With serious diseases such as congestive heart failure, uncontrolled myocardial infarction and arrhythmia, liver failure and renal failure.
* With neurological or psychiatric abnormalities that affect cognitive.
* Pregnant or lactated women (premenopausal women must give urine pregnancy test before enrollment)

Primary outcomes:
measure: Disease-free survival
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years
measure: Pathological complete response of neoadjuvant treatment
timeFrame: 4 months
measure: The R0 resection rate
timeFrame: 3 months
measure: Numbers of adverse events and the degree of each adverse events according to the NCI CTCAE 4.0 criteria.
timeFrame: 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital & Peking University Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Xiaodong Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: