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Gastrointestinal Neoplasms

Digestive System Neoplasms

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Gastrointestinal Diseases

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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

Treatment options Nimotuzumab （400mg plus normal saline 250ml intravenous infusion for not less than 60 minutes. Starting from week 1 of radiotherapy, 1 dose of the same dose each time for a total of 6 doses）combined with chemoradiotherapy (Oral chemotherapy with the tigio regimen is given on days 1 to 2 of radiotherapy, with the drug dose calculated based on body surface area, and the oral tigio course from Monday to Friday is synchronized with radiation therapy) for the treatment of locally advanced elderly esophageal cancer patients, in which the tigio regimen with good clinical tolerability was selected for chemotherapy to evaluate the short-term efficacy and toxic side effects

Nimotuzumab 400mg plus normal saline 250ml intravenous infusion for not less than 60 minutes. Starting from week 1 of radiotherapy, 1 dose of the same dose each time for a total of 6 doses. The use of Taixinsen is not interrupted due to interruption of radiotherapy during the administration until the end of radiotherapy.

Oral chemotherapy with the tigio regimen is given on days 1 to 2 of radiotherapy, with the drug dose calculated based on body surface area, and the oral tigio course from Monday to Friday is synchronized with radiation therapy.

Tigio

Outline the target area layer by layer on the enhanced CT image, PGTV, PTV. The endangered organs are delineated layer by layer on the cross-section, and extended 0.3cm to form a corresponding plan to endanger the organs. The reverse intensity modulated radiotherapy plan was designed on the Monaco treatment plan system, with a prescribing dose of 56Gy/30F for PTV and 60Gy/30F for pGTV, and the target dose distribution and organ exposure dose were evaluated layer by layer on a cross-sectional surface, and combined with dose-to-volume histogram (DVH) evaluation and optimal treatment plan, the maximum dose of radiation in the spinal cord \< 40 Gy and lung V20\<30%. After the treatment plan is confirmed, the dose is verified on the treatment machine, and the treatment plan is executed after it is accurate. govern

Concurrent radiation therapy

Xiaolin GE, PhD

The research subjects of this project are mainly aimed at patients with locally advanced esophageal cancer who cannot be treated surgically, in Taixinsheng 3 months after the end of concurrent chemoradiotherapy, RECIST is pressed as based on physical examination and esophageal barium dialysis or esophageal contrast-enhanced CT Criteria assessed short-term and long-term efficacy separately. By detecting the expression of EGFR in patients with locally advanced esophageal cancer, the relationship between the efficacy of EGFR monoclonal antibody therapy and the long-term prognosis of patients was evaluated. Evaluation of safety, toxicity and side effects during treatment and in the near and long term.

It is expected that 45 patients will be enrolled, and patients who meet the enrollment criteria will undergo esophagoscopy, esophageal barium meal examination, chest contrast-enhanced CT, abdominal ultrasound, electrocardiogram, blood routine, whole body bone scan, liver and kidney function and other examinations before treatment, and esophageal ultrasound if necessary. Patients who received esophageal ultrasound were staged by esophageal ultrasound results, and those without esophageal ultrasound were mainly staged according to the cervical chest and epigastric contrast CT and esophageal barium plates, and clinical staging was performed according to the 2002 AJCC staging standard. After the combination of Taixinsheng and concurrent chemoradiotherapy, adverse reactions and efficacy evaluation were observed. The expected result is that the local control rate of EGFR monoclonal antibody combined with chemoradiotherapy is improved in patients with locally advanced elderly esophageal squamous cell carcinoma, and there is no significant increase in adverse reactions, and serological indicators such as EGFR can be used as prognostic indicators for esophageal malignancy and have certain guiding significance for treatment. EGFR monoclonal antibody can be used in locally advanced elderly esophageal cancer patients who cannot tolerate chemotherapy, with good short-term efficacy and tolerable toxic side effects, which further provides reference value for clinical guidance.

Nimotuzumab Combined With Concurrent Chemoradiotherapy for Locally Advanced Treatment Esophageal Cancer in Old Age

Overall survival was measured from the initiation of chemotherapy to the date of the last follow-up or death.

After treatment, the lesion completely disappears, or all symptoms and signs of the unmeasurable lesion completely disappear, and the lesion completely disappears in X-ray and bone imaging examinations for bone metastasis, lasting for at least 4 weeks

The sum of the maximum diameters of the target lesion decreases by more than 30% and lasts for more than 4 weeks.

At the end of radiotherapy, there is residual tumor or no significant improvement in the lesion, but there are still significant filling defects and worsening of niche or stenosis

The US Toxicity Evaluation Standard (CTC3. O) is divided into O\~4 grades, and the evaluation of acute radiation reactions adopts RTOG/EROTC criteria

Bevacizumab

Angiogenesis Inhibitors

Growth Inhibitors

A non-randomized, non-blinded, prospective, feasibility study.

* IV-administration of 4.5 mg of the fluorescent tracer bevacizumab-800CW to a total of 5 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
* Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.

A non-randomized, non-blinded, prospective, feasibility study.

* IV-administration of 10 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
* Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.

A non-randomized, non-blinded, prospective, feasibility study.

* IV-administration of 25 mg of the fluorescent tracer bevacizumab-800CW to a total of 3 patients with locally advanced esophageal cancer. The optimal dose will be expanded to include 30 patients.
* Molecular fluorescence endoscopy: 2-3 days after administration, molecular fluorescence endoscopy will be performed with additional measurements of fluorescence signals.

Intravenous administration of 4.5, 10 or 25 mg of Bevacizumab-IRDye800CW prior to the endoscopic procedure

Bevacizumab-IRDye800CW

A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working channel of the standard clinical endoscope. Fluorescence imaging will be performed prior to and post the chemoradiotherapy.

Molecular Fluorescence Endoscopy platform

W. B. Nagengast, MD, PhD, PharmD

G. M. van Dam, MD, PhD

For locally advanced esophageal cancer (EC), neoadjuvant chemoradiotherapy (nCRT) for 5 weeks followed by esophagectomy and lymphadenectomy, if necessary, is standard of care. It is reported that the pathological complete response (pCR) rate after nCRT ranges from 16% to 43%, with a median of 26.5%. According to current clinical guidelines, patients who achieved pCR still go for surgery even though those patients who achieved pCR may not benefit from surgery. Besides, about 50% of EC patients may have post-operative complications including pneumonia, anastomotic leakage, recurrent laryngeal nerve paralysis, which lead to low health-related quality of life (HQoL).

The golden standard to test the pathological response is by pathological assessment of the surgical specimen and thus after surgery. Theoretically, if pCR after nCRT can be predicted accurately before surgery by advanced imaging techniques, patients could have a wait-and-see. The wait-and-see procedure includes regular follow-up and salvage surgery if recurrence is present. Therefore, molecular fluorescence endoscopy (FME) using near-infrared fluorescence (NIRF) tracer bevacizumab-800CW targeting vascular endothelial growth factor combined with high-definition white light (HD-WL) endoscopy is expected to be a promising technique to monitor pCR and fill the gap.

Fluorescence Endoscopy of Esophageal Carcinoma

Fluorescence Molecular Endoscopy of Locally Advanced Esophageal Carcinoma Using Bevacizumab-800CW to Evaluate Dose Response After Neoadjuvant Chemoradiotherapy: a Single-center Feasibility Study.

To determine the sensitivity of the marker bevacizumab-800CW in discriminating between tumorous and non-tumorous tissue prior to and post neoadjuvant chemoradiotherapy, to identify patients who benefit from the chemoradiotherapy.

Monitoring vital signs (blood pressure, heart frequency and temperature) and/or (serious) adverse events that are related to the administration of bevacizumab-800CW

Correlate the H/E images to the fluorescent images made with multiple ex vivo imaging modalities.

Multi-diameter single-fiber reflectance with single-fiber fluorescence (MDSFR/SFF) spectroscopy can measure the fluorescence signal quantitatively, both in vivo and ex vivo.

CLE is a confocal laser endomicroscopy system which enables in vivo microscopic images of the tissue

Imaging of the distribution of bevacizumab-800CW with a fluorescence microscoop.

Both the images and specific measurements are used to calculate the fluorescence intensity (TBR \& intrinsic fluorescence) and a difference between the before and after intensity is calculated.

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
Nimotuzumab Combined With Concurrent Chemoradiotherapy for Locally Advanced Treatment Esophageal Cancer in Old Age	NCT06048913	Esophageal Carc...	Nimotuzumab Tigio Concurrent radi...	70 Years -	The First Affiliated Hospital with Nanjing Medical University
Fluorescence Endoscopy of Esophageal Carcinoma	NCT03558724	Esophageal Canc...	Bevacizumab-IRD... Molecular Fluor...	18 Years -	University Medical Center Groningen
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
Fluorescence Endoscopy of Esophageal Carcinoma	NCT03558724	Esophageal Canc...	Bevacizumab-IRD... Molecular Fluor...	18 Years -	University Medical Center Groningen
Nimotuzumab Combined With Concurrent Chemoradiotherapy for Locally Advanced Treatment Esophageal Cancer in Old Age	NCT06048913	Esophageal Carc...	Nimotuzumab Tigio Concurrent radi...	70 Years -	The First Affiliated Hospital with Nanjing Medical University

Spots Global Cancer Trial Database for locally advanced esophageal cancer