Simultaneous Integrated Boost Radiotherapy and Concurrent Nimotuzumab or Chemotherapy for Esophageal Carcinoma

Study Overview
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Brief Summary
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This prospective, non-randomized phase II study aims to compare radiotherapy and concurrent nimotuzumab with concurrent chemoradiotherapy to obtain a non-inferior pCR rate and pathological lymph node metastases rate in premise of lower toxicities in locally advanced esophageal cancer.

Detailed Description
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In the era of IMRT and concurrent chemoradiotherapy, the 5-year overall survival of esophageal cancer increase from 10% to about 20%-40%, recurrence rate decrease from 80% to 50%-60%, and local recurrence remains to be the most important type of failure. What called for is to enhance local control without increasing toxicity to improve survival. The investigators have found effective and safe regimen of simultaneously integrated boost radiotherapy in previous study, which can achieve high dose in tumor area with avoid of normal tissues. However, a recent prospective study reported that neoadjuvant chemoradiotherapy resulted in much higher toxicities compares to neoadjuvant chemotherapy (46% vs. 15%, p= 0.04). Although chemoradiotherapy reached a higher pCR rate (28% vs. 9%, p=0.002), patients did not differ in survival in two groups. Nimotuzumab is an humanized monoclonal antibody against EGFR. Radiotherapy combines Nimotuzumab reveals synergistic effect in head and neck cancers with lower toxicities as compared to concurrent chemoradiotherapy. Our previous study showed that EGFR expression rate were similar in esophageal cancer and head and neck cancers. Based on above results, the investigators design this study which aims to obtain a non-inferior pCR rate and pathological lymph node metastases rate in premise of lower toxicities.

Official Title
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Prospective, Non-randomised Phase Ⅱ Study of Simultaneous Integrated Boost Radiotherapy and Concurrent Nimotuzumab or Chemotherapy for Locally Advanced Esophageal Carcinoma

Conditions
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Esophageal Neoplasms

Intervention / Treatment
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* Radiation: IMRT simultaneous integrated boost
* Drug: Nimotuzumab
* Drug: Paclitaxel
* Drug: Nedaplatin
* Procedure: Esophagectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of clinical stage T1-4aN0-1M1a untreated squamous esophageal carcinoma KPS≥70 Adequate organ function No known history of drug allergy Exclusion Criteria: Known drug allergy Insufficient hepatorenal function Severe cardiovascular diseases, diabetes with uncontrolled blood sugar, mental disorders, uncontrolled severe infection, active ulceration which need intervention.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant nimotuzumab<br>Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent nimotuzumab: Patients may receive nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity. Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication. | Radiation: IMRT simultaneous integrated boost<br>* To achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively<br>Drug: Nimotuzumab<br>* nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks<br>Procedure: Esophagectomy<br>* Radical esophagectomy 4-6 weeks after neoadjuvant therapy<br>|
| Active Comparator: Neoadjuvant chemotherapy<br>Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 4.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity. Assessment of surgery: Patients eligible for surgery after multiple disciplinary consultation will receive esophagectomy after a 4-6 weeks break after chemoradiation in the absence of any contraindication. | Radiation: IMRT simultaneous integrated boost<br>* To achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively<br>Drug: Paclitaxel<br>* Paclitaxel from 45 to 60 mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks<br>* Other names: Taxol;Drug: Nedaplatin<br>* Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks<br>Procedure: Esophagectomy<br>* Radical esophagectomy 4-6 weeks after neoadjuvant therapy<br>|
| Experimental: Radical nimotuzumab<br>Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent nimotuzumab: Patients may receive nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity. | Radiation: IMRT simultaneous integrated boost<br>* To achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively<br>Drug: Nimotuzumab<br>* nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks<br>|
| Active Comparator: Radical chemotherapy<br>Radiation：Patients undergo radiotherapy once daily 5 days a week for an average of 5.5 weeks in the absence of disease progression or unacceptable toxicity. IMRT simultaneous integrated boost is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively. Concurrent chemotherapy: Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks after enrollment in the absence of disease progression or unacceptable toxicity. | Radiation: IMRT simultaneous integrated boost<br>* To achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively<br>Drug: Paclitaxel<br>* Paclitaxel from 45 to 60 mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks<br>* Other names: Taxol;Drug: Nedaplatin<br>* Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate |  | Up to 1 year | 
| Pathological lymph node metastases rate |  | Up to 1 year | 
| R0 resection rate |  | Up to 1 year | 
| Adverse events |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) |  | Up to 2 years | 
| Overall survival (OS) |  | Up to 2 years | 
| Recurrence rate |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced esophageal cancer, Radiotherapy and nimotuzumab, Concurrent chemoradiotherapy