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

Primary Purpose

Esophageal Squamous Cell Carcinoma

Status

Withdrawn

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Nimotuzumab

Paclitaxel

Cisplatin

Radiation

Surgery

About this trial

This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma focused on measuring Esophageal Squamous Cell Carcinoma, Nimotuzumab, Neoadjuvant treatment

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Beijing Cancer Hospital & Peking University Cancer Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Nimotuzumab with Chemotherapy

Nimotuzumab with radiotherapy

Surgery alone

Arm Description

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.

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.

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

Outcomes

Primary Outcome Measures

Disease-free survival

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

Overall survival

From the date of randomization until the date of death from any cause. An expected average of 3 years.

Pathological complete response of neoadjuvant treatment

From the date of randomization until the date of pathological diagnosis is reported after esophagectomy. An expected average of 4 months.

The R0 resection rate

From the date of randomization to one week after the surgical resection of tumor (esophagectomy). An expected average of 3 months.

Numbers of adverse events and the degree of each adverse events according to the NCI CTCAE 4.0 criteria.

From the date of randomization to 3 months after esophagectomy. An expected average of 6 months.

Full Information

NCT ID

NCT02272699

First Posted

October 11, 2014

Last Updated

March 16, 2021

Sponsor

Peking University

1. Study Identification

Unique Protocol Identification Number

NCT02272699

Brief Title

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

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Withdrawn

Why Stopped

Because there are questions about adjuvant radiotherapy in this study, the clinical trial is under re-design.

Study Start Date

November 2014 (undefined)

Primary Completion Date

December 2020 (Actual)

Study Completion Date

December 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Esophageal Squamous Cell Carcinoma

Keywords

Esophageal Squamous Cell Carcinoma, Nimotuzumab, Neoadjuvant treatment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nimotuzumab with Chemotherapy

Arm Type

Experimental

Arm Description

Arm Title

Nimotuzumab with radiotherapy

Arm Type

Experimental

Arm Description

Arm Title

Surgery alone

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Nimotuzumab

Other Intervention Name(s)

h-R3

Intervention Description

Nimotuzumab 200mg per week for 6 weeks.

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Taxol

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

CDDP

Intervention Description

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

Intervention Type

Radiation

Intervention Name(s)

Radiation

Intervention Description

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

Procedure

Intervention Name(s)

Surgery

Intervention Description

Esophagectomy

Primary Outcome Measure Information:

Title

Disease-free survival

Description

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.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Overall survival

Description

From the date of randomization until the date of death from any cause. An expected average of 3 years.

Time Frame

3 years

Title

Pathological complete response of neoadjuvant treatment

Description

From the date of randomization until the date of pathological diagnosis is reported after esophagectomy. An expected average of 4 months.

Time Frame

4 months

Title

The R0 resection rate

Description

From the date of randomization to one week after the surgical resection of tumor (esophagectomy). An expected average of 3 months.

Time Frame

3 months

Title

Numbers of adverse events and the degree of each adverse events according to the NCI CTCAE 4.0 criteria.

Description

From the date of randomization to 3 months after esophagectomy. An expected average of 6 months.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xiaodong Zhang, M.D.

Organizational Affiliation

Peking University Cancer Hospital & Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Beijing Cancer Hospital & Peking University Cancer Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100142

Country

China

12. IPD Sharing Statement

Learn more about this trial

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

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