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

NCT ID: NCT02858206

Last Updated: 2019-07-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2021-11-30

Brief Summary

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

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.

Conditions

Esophageal Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant nimotuzumab

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.

Group Type: EXPERIMENTAL

IMRT simultaneous integrated boost

Intervention Type: RADIATION

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

Nimotuzumab

Intervention Type: DRUG

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

Esophagectomy

Intervention Type: PROCEDURE

Radical esophagectomy 4-6 weeks after neoadjuvant therapy

Neoadjuvant chemotherapy

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.

Group Type: ACTIVE_COMPARATOR

IMRT simultaneous integrated boost

Intervention Type: RADIATION

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

Paclitaxel

Intervention Type: DRUG

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

Nedaplatin

Intervention Type: DRUG

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

Esophagectomy

Intervention Type: PROCEDURE

Radical esophagectomy 4-6 weeks after neoadjuvant therapy

Radical nimotuzumab

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.

Group Type: EXPERIMENTAL

IMRT simultaneous integrated boost

Intervention Type: RADIATION

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

Nimotuzumab

Intervention Type: DRUG

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

Radical chemotherapy

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.

Group Type: ACTIVE_COMPARATOR

IMRT simultaneous integrated boost

Intervention Type: RADIATION

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

Paclitaxel

Intervention Type: DRUG

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

Nedaplatin

Intervention Type: DRUG

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

Interventions

IMRT simultaneous integrated boost

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

Intervention Type: RADIATION

Nimotuzumab

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

Intervention Type: DRUG

Paclitaxel

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

Intervention Type: DRUG

Nedaplatin

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

Intervention Type: DRUG

Esophagectomy

Radical esophagectomy 4-6 weeks after neoadjuvant therapy

Intervention Type: PROCEDURE

Other Intervention Names

Taxol

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hebei Medical University Fourth Hospital

OTHER

Sponsor Role: collaborator

Affiliated Hospital of Hebei University

OTHER

Sponsor Role: collaborator

Beijing Army General Hospital

OTHER_GOV

Sponsor Role: collaborator

Beijing Hospital

OTHER_GOV

Sponsor Role: collaborator

Peking University First Hospital

OTHER

Sponsor Role: collaborator

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: collaborator

Henan Cancer Hospital

OTHER_GOV

Sponsor Role: collaborator

The Affiliated Hospital of Inner Mongolia Medical University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: collaborator

Fujian Cancer Hospital

OTHER_GOV

Sponsor Role: collaborator

Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Zefen Xiao

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Zefen Xiao

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zefen Xiao, MD

Role: CONTACT

xiaozefen@sina.com

8610-87787643

Wei Deng, MD

Role: CONTACT

sherrydw@126.com

+8618813019080

Facility Contacts

Zefen Xiao, MD

Role: primary

xiaozefen@sina.com

8610-87787643

Wei Deng, MD

Role: backup

sherrydw@126.com

+8618813019080

References

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

PMID: 21462364 (View on PubMed)

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Reference Type: RESULT

PMID: 14967459 (View on PubMed)

Ramos-Suzarte M, Lorenzo-Luaces P, Lazo NG, Perez ML, Soriano JL, Gonzalez CE, Hernadez IM, Albuerne YA, Moreno BP, Alvarez ES, Callejo IP, Alert J, Martell JA, Gonzalez YS, Gonzalez YS, Astudillo de la Vega H, Ruiz-Garcia EB, Ramos TC. Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Cancer Biol Ther. 2012 Jun;13(8):600-5. doi: 10.4161/cbt.19849. Epub 2012 Jun 1.

Reference Type: RESULT

PMID: 22555809 (View on PubMed)

Other Identifiers

16-082/1161

Identifier Type: -

Identifier Source: org_study_id