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

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Completed; Phase 2; Phase 1

Conditions: Esophageal Neoplasms

Treatments: Radiation: IMRT simultaneous integrated boost; Procedure: Esophagectomy; Drug: Paclitaxel; Drug: Nedaplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT02429622

14-133/923

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 80 patients

Sex: All

Ages: 18 to 72 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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80 participants in 4 patient groups

Radical 2.14

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Nedaplatin

Radiation: IMRT simultaneous integrated boost

Radical 2.17

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Nedaplatin

Radiation: IMRT simultaneous integrated boost

Radical 2.21

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Nedaplatin

Radiation: IMRT simultaneous integrated boost

Neoadjuvant 2.14

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Nedaplatin

Procedure: Esophagectomy

Radiation: IMRT simultaneous integrated boost