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

March 16, 2021 updated by: Xiaodong Zhang, Peking University

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100142
        • Beijing Cancer Hospital & Peking University Cancer Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Procedure: Surgery
Esophagectomy
Drug: Nimotuzumab
Nimotuzumab 200mg per week for 6 weeks.
Other Names:
  • h-R3
Drug: Paclitaxel
Paclitaxel 175mg per square metre on day 1, repeated every 3 weeks for 2 cycles.
Other Names:
  • Taxol
Drug: Cisplatin
Cisplatin 30mg per square metre on day 1 and day 2, repeated every 3 weeks for 2 cycles.
Other Names:
  • CDDP
Experimental: 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.
Drug: Nimotuzumab
Nimotuzumab 200mg per week for 6 weeks.
Other Names:
  • h-R3
Radiation: Radiation
IMRT of primary tumor and local lymph nodes with 95% PTV of 41.4 Gy/23f. Nimotuzumab 200mg per week for 6 weeks.
Active Comparator: 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.
Procedure: Surgery
Esophagectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival
Time Frame: 2 years
From the date of randomization until the date of first documented relapse of disease or date of death from any cause, whichever came first. An expected average of 2 years.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 3 years
From the date of randomization until the date of death from any cause. An expected average of 3 years.
3 years
Pathological complete response of neoadjuvant treatment
Time Frame: 4 months
From the date of randomization until the date of pathological diagnosis is reported after esophagectomy. An expected average of 4 months.
4 months
The R0 resection rate
Time Frame: 3 months
From the date of randomization to one week after the surgical resection of tumor (esophagectomy). An expected average of 3 months.
3 months
Numbers of adverse events and the degree of each adverse events according to the NCI CTCAE 4.0 criteria.
Time Frame: 6 months
From the date of randomization to 3 months after esophagectomy. An expected average of 6 months.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University

Investigators

  • Principal Investigator: Xiaodong Zhang, M.D., Peking University Cancer Hospital & Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

December 1, 2020

Study Completion (Actual)

December 1, 2020

Study Registration Dates

First Submitted

October 11, 2014

First Submitted That Met QC Criteria

October 21, 2014

First Posted (Estimate)

October 23, 2014

Study Record Updates

Last Update Posted (Actual)

March 18, 2021

Last Update Submitted That Met QC Criteria

March 16, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ESCC002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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