Neoadjuvant Treatment of Nimotuzumab With Chemotherapy or Radiotherapy in Resectable Esophageal Squamous Cell Carcinoma

NCT ID: NCT02272699

Last Updated: 2021-03-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2020-12-31

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.

Conditions

Esophageal Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nimotuzumab with Chemotherapy

Patients will receive neoadjuvant chemotherapy of paclitaxel and cisplatin with concurrent nimotuzumab.

Paclitaxel 175mg per square metre on day 1 and cisplatin 30mg per square metre on day 1 and day 2 every 3 weeks for 2 cycles. Nimotuzumab 200mg per week for 6 weeks.

After neoadjuvant treatment, patients will be evaluated by a multidisciplinary teams (MDTs) and esophagectomy will be given for patients with resectable disease.

Group Type: EXPERIMENTAL

Nimotuzumab

Intervention Type: DRUG

Nimotuzumab 200mg per week for 6 weeks.

Paclitaxel

Intervention Type: DRUG

Paclitaxel 175mg per square metre on day 1, repeated every 3 weeks for 2 cycles.

Cisplatin

Intervention Type: DRUG

Cisplatin 30mg per square metre on day 1 and day 2, repeated every 3 weeks for 2 cycles.

Surgery

Intervention Type: PROCEDURE

Esophagectomy

Nimotuzumab with radiotherapy

Patients will receive neoadjuvant radiotherapy with concurrent nimotuzumab. Intensity-modulated radiation therapy(IMRT) of primary tumor and local lymph nodes with 95% planning target volume (PTV) of 41.4 Gy/23f. Nimotuzumab 200mg per week for 6 weeks.

After neoadjuvant treatment, patients will be evaluated by a multidisciplinary teams (MDTs) and esophagectomy will be given for patients with resectable disease.

Group Type: EXPERIMENTAL

Nimotuzumab

Intervention Type: DRUG

Nimotuzumab 200mg per week for 6 weeks.

Radiation

Intervention Type: RADIATION

IMRT of primary tumor and local lymph nodes with 95% PTV of 41.4 Gy/23f. Nimotuzumab 200mg per week for 6 weeks.

Surgery alone

Patients in this group will be given esophagectomy without any neoadjuvant treatment. Adjuvant radiotherapy is permit for patients with positive lymph nodes metastasis.

Group Type: ACTIVE_COMPARATOR

Surgery

Intervention Type: PROCEDURE

Esophagectomy

Interventions

Nimotuzumab

Nimotuzumab 200mg per week for 6 weeks.

Intervention Type: DRUG

Paclitaxel

Paclitaxel 175mg per square metre on day 1, repeated every 3 weeks for 2 cycles.

Intervention Type: DRUG

Cisplatin

Cisplatin 30mg per square metre on day 1 and day 2, repeated every 3 weeks for 2 cycles.

Intervention Type: DRUG

Radiation

IMRT of primary tumor and local lymph nodes with 95% PTV of 41.4 Gy/23f. Nimotuzumab 200mg per week for 6 weeks.

Intervention Type: RADIATION

Surgery

Esophagectomy

Intervention Type: PROCEDURE

Other Intervention Names

h-R3; Taxol; CDDP

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University

OTHER

Sponsor Role: lead

Responsible Party

Xiaodong Zhang

Dean of the VIP-II Gastrointestinal Oncology Division of Medical Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiaodong Zhang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Peking University Cancer Hospital & Institute

Locations

Beijing Cancer Hospital & Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

ESCC002

Identifier Type: -

Identifier Source: org_study_id