Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02272699
Recruitment Status : Suspended (Because there are questions about adjuvant radiotherapy in this study, the clinical trial is under re-design.)
First Posted : October 23, 2014
Last Update Posted : April 7, 2017
Sponsor:
Information provided by (Responsible Party):
Xiaodong Zhang, Peking University

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.


Condition or disease Intervention/treatment Phase
Esophageal Squamous Cell Carcinoma Drug: Nimotuzumab Drug: Paclitaxel Drug: Cisplatin Radiation: Radiation Procedure: Surgery Phase 2 Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 195 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Treatment of Nimotuzumab With Chemotherapy or Radiotherapy Versus Surgery Alone in Resectable Esophageal Squamous Cell Carcinoma
Study Start Date : November 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


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.

Drug: Nimotuzumab
Nimotuzumab 200mg per week for 6 weeks.
Other Name: h-R3

Drug: Paclitaxel
Paclitaxel 175mg per square metre on day 1, repeated every 3 weeks for 2 cycles.
Other Name: Taxol

Drug: Cisplatin
Cisplatin 30mg per square metre on day 1 and day 2, repeated every 3 weeks for 2 cycles.
Other Name: CDDP

Procedure: Surgery
Esophagectomy

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 Name: 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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02272699


Locations
Layout table for location information
China, Beijing
Beijing Cancer Hospital & Peking University Cancer Hospital
Beijing, Beijing, China, 100142
Sponsors and Collaborators
Peking University
Investigators
Layout table for investigator information
Principal Investigator: Xiaodong Zhang, M.D. Beijing Cancer Hospital

Layout table for additonal information
Responsible Party: Xiaodong Zhang, Dean of the VIP-II Gastrointestinal Oncology Division of Medical Department, Peking University
ClinicalTrials.gov Identifier: NCT02272699    
Other Study ID Numbers: ESCC002
First Posted: October 23, 2014    Key Record Dates
Last Update Posted: April 7, 2017
Last Verified: April 2017
Keywords provided by Xiaodong Zhang, Peking University:
Esophageal Squamous Cell Carcinoma
Nimotuzumab
Neoadjuvant treatment
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Nimotuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological