Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Nimotuzumab

Albumin-Bound Paclitaxel

Nedaplatin

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

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：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：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：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.

To achieve a prophylactic dosage and radical dosage of 1.8Gy and 2.14Gy once respectively

IMRT simultaneous integrated boost

nimotuzumab 400mg per week which start from 1 week before radiotherapy and in the following 4 weeks

Paclitaxel from 45 to 60 mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks

Nedaplatin 25mg/m2 per week which start from 1 week before radiotherapy and in the following 4 weeks

Radical esophagectomy 4-6 weeks after neoadjuvant therapy

Esophagectomy

Zefen Xiao, MD

Wei Deng, MD

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.

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.

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

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

Hebei Medical University Fourth Hospital

Affiliated Hospital of Hebei University

Beijing Army General Hospital

Beijing Hospital

Peking University First Hospital

Tianjin Medical University Cancer Institute and Hospital

Henan Cancer Hospital

The Affiliated Hospital of Inner Mongolia Medical University

The First Affiliated Hospital with Nanjing Medical University

Fujian Cancer Hospital

Chinese Academy of Medical Sciences

Professor

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：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：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：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.

To achieve a prophylactic dosage and radical dosage once respectively

Paclitaxel from 45 to 60 mg/m2 per week concurrent with radiotherapy for 5weeks

Nedaplatin 25mg/m2 per week concurrent with radiotherapy for 5weeks

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Simultaneous Integrated Boost Radiotherapy and Concurrent Nimotuzumab or Chemotherapy for Esophageal Carcinoma	NCT02858206	Esophageal Neop...	IMRT simultaneo... Nimotuzumab Paclitaxel Nedaplatin Esophagectomy	18 Years - 69 Years	ChineseAMS
Simultaneous Integrated Boost Radiotherapy and Concurrent Nimotuzumab or Chemotherapy for Esophageal Carcinoma	NCT02858206	Esophageal Neop...	IMRT simultaneo... Nimotuzumab Paclitaxel Nedaplatin Esophagectomy	18 Years - 69 Years	ChineseAMS
Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy for Locally Advanced Esophageal Carcinoma	NCT02429622	Esophageal Neop...	IMRT simultaneo... Paclitaxel Nedaplatin Esophagectomy	18 Years - 72 Years	ChineseAMS
Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy for Locally Advanced Esophageal Carcinoma	NCT02429622	Esophageal Neop...	IMRT simultaneo... Paclitaxel Nedaplatin Esophagectomy	18 Years - 72 Years	ChineseAMS
Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy for Locally Advanced Esophageal Carcinoma	NCT02429622	Esophageal Neop...	IMRT simultaneo... Paclitaxel Nedaplatin Esophagectomy	18 Years - 72 Years	ChineseAMS

Spots Global Cancer Trial Database for imrt simultaneous integrated boost