Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy for Locally Advanced Esophageal Carcinoma

Study Overview
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Brief Summary
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This phase Ⅰ/Ⅱ trial is designed to explore a higher radiation dose by using IMRT simultaneous integrated boost technique with or without concurrent chemotherapy for locally advanced esophageal carcinoma.

Detailed Description
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Despite the application of IMRT and the studies of concurrent chemoradiation in esophageal carcinoma, which improves 5-year survival rate from 10% to 20%-40% and decrease recurrence rate from 80% to 50%-60%, local recurrence remains to be the most common failure pattern. Therefore, enhancing local control is the key to obtain a better survival. A phase Ⅱ study of radical radiotherapy with IMRT simultaneous integrated boost technique and concurrent chemotherapy for esophageal carcinoma use the same radiation dose as the high dose arm in RTOG 94-05, which reveals an significantly improved median survival time of 23 months and 3-year overall survival rate of 44.4%. This study implies the simultaneous integrated boost technique may be effective to some extent. But the question is how to identify patients who may gain potential benefits, and whether this therapeutic model can be copied in the specific situation in China? Few adverse effects such as perforation, hemorrhage and stenosis was reported, mainly owing to the lack of cases. For widely application of this new technique in the clinic, more studies need to be conducted in the future to obtain sufficient evidence. The current IMRT can simultaneously achieve prophylactic dose (DT 50Gy) and radical dose (DT 60-64Gy) in respective target volume by using inverse intensity-modulated planning system. However, it is still controversial on whether esophageal carcinoma can receive prescription dose more than 2.0Gy each time. That is to say, it is challengeable to find an optimal fraction dose and total dose between tumor and adverse effects. For this reason, the dose escalation trial is to be conducted to explore the clinical value and optimal dose to esophageal carcinoma with different radiosensitivity, and also provide data support for phase Ⅲ clinical trials.

Official Title
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A Phase Ⅰ/Ⅱ Study of Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy in Patients With Locally Advanced Esophageal Carcinoma

Conditions
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Esophageal Neoplasms

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of clinical stage T2-4N0-1M1a 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: 72 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radical 2.14<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 technique 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 in the following 5 weeks after enrollment with radiotherapy at the same time in the absence of disease progression or unacceptable toxicity. | Radiation: IMRT simultaneous integrated boost<br>* To achieve a prophylactic dosage and radical dosage once respectively<br>Drug: Paclitaxel<br>* Paclitaxel from 45 to 60 mg/m2 per week concurrent with radiotherapy for 5weeks<br>* Other names: Taxel;Drug: Nedaplatin<br>* Nedaplatin 25mg/m2 per week concurrent with radiotherapy for 5weeks<br>|
| Experimental: Radical 2.17<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 technique is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.17Gy once respectively. Concurrent chemotherapy:Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week in the following 5 weeks after enrollment with radiotherapy at the same time in the absence of disease progression or unacceptable toxicity. | Radiation: IMRT simultaneous integrated boost<br>* To achieve a prophylactic dosage and radical dosage once respectively<br>Drug: Paclitaxel<br>* Paclitaxel from 45 to 60 mg/m2 per week concurrent with radiotherapy for 5weeks<br>* Other names: Taxel;Drug: Nedaplatin<br>* Nedaplatin 25mg/m2 per week concurrent with radiotherapy for 5weeks<br>|
| Experimental: Radical 2.21<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 technique is used to achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.21Gy once respectively. Concurrent chemotherapy:Patients may receive a dosage range of Paclitaxel from 45 to 60 mg/m2 and Nedaplatin 25mg/m2 per week in the following 5 weeks after enrollment with radiotherapy at the same time in the absence of disease progression or unacceptable toxicity. | Radiation: IMRT simultaneous integrated boost<br>* To achieve a prophylactic dosage and radical dosage once respectively<br>Drug: Paclitaxel<br>* Paclitaxel from 45 to 60 mg/m2 per week concurrent with radiotherapy for 5weeks<br>* Other names: Taxel;Drug: Nedaplatin<br>* Nedaplatin 25mg/m2 per week concurrent with radiotherapy for 5weeks<br>|
| Experimental: Neoadjuvant 2.14<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 technique 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 in the following 4 weeks after enrollment with radiotherapy at the same time 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 once respectively<br>Drug: Paclitaxel<br>* Paclitaxel from 45 to 60 mg/m2 per week concurrent with radiotherapy for 5weeks<br>* Other names: Taxel;Drug: Nedaplatin<br>* Nedaplatin 25mg/m2 per week concurrent with radiotherapy for 5weeks<br>Procedure: Esophagectomy<br>* Radical esophagectomy 4-6 weeks after neoadjuvant therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) |  | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) |  | up to 5 years |