Study of Neo-adjuvant Chemoradiotherapy Followed by Minimally Invasive Esophagectomy for Squamous Cell Esophageal Cancer (NACRFMIE)

A Single Institution Prospective Randomized Controlled Clinical Trial of Neo-adjuvant Chemoradiotherapy Followed by Mckeown Minimally Invasive Esophagectomy (MIE) Versus Mckeown MIE for Locally Advanced Squamous Cell Esophageal Carcinoma

The primary objective is to compare neo-adjuvant chemoradiotherapy followed by Mckeown Minimally Invasive Esophagectomy (MIE) Versus Mckeown MIE, pure radical chemoradiotherapy in terms of the overall survival time (OS) in patients with Stage IIB or III squamous cell esophageal carcinoma.

Study Overview

• Status: Unknown
• Conditions: Squamous Cell Esophageal Carcinoma
• Intervention / Treatment: Procedure: Neo-adjuvant Chemoradiotherapy followed by Mckeown MIE; Drug: Cisplatin; Device: Mckeown MIE

Detailed Description

Esophageal cancer is one of the most difficult malignancies to cure. Surgical resection remains the primary treatment for localized esophageal cancer. It increases the chances of cure and alleviates the symptoms of dysphagia compared with nonoperative methods. Advances in surgical techniques and equipments have made minimally invasive esophagectomy (MIE) more popular and wider application since 1990s. During the past two decades, MIE has progressively been accepted as an alternative treatment for esophageal cancer around the world. The prognosis has some improvement on account of these significant advances in surgical techniques and perioperative management, But the prognosis of patients with locally advanced esophageal cancer remains rather poor. As a result of surgery alone, the 5-year survival rate of about 25% has not changed significantly in several decades.

Preoperative chemoradiotherapy followed by surgery seems to hopefully improve the survival of EC. Nevertheless, the results of different studies were inconsistent. Recently, the CROSS trial has demonstrated that preoperative chemoradiotherapy can significantly increased the overall survival of patients with EC compared with surgery alone. It should be noticed that only 84 cases(23%) of ESCC were enrolled in this trial with potential minimal follow-up of 2 years, which may be not perfect to evaluate the effect of this combined therapy for this tumor type.

Based on our preliminary study, we have demonstrated the validity and safety of vinorelbine and cisplatin-based neoadjuvant chemoradiotherapy. Then we are to carry out a clinical trial to investigate the effect of this multidisciplinary therapy, by comparing neo-adjuvant chemoradiotherapy followed by Mckeown MIE versus Mckeown MIE, pure radical chemoradiotherapy in terms of the overall survival time (OS) in patients with Stage IIB or III squamous cell esophageal carcinoma.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cheng chu Zhu, professor; Phone Number: 86-576-85199876; Email: zhucc669266@163.com
• Study Contact Backup: Name: min Kong, master; Phone Number: 86-576-85199101; Email: kongm@enzemed.com

Study Locations

• China
  • Zhejiang
    • Linhai, Zhejiang, China, 317000
      • Recruiting
      • Thaizhou Hospital
      • Contact: Cheng chu Zhu, professor; Phone Number: +86-576-85199876; Email: zhucc669266@163.com
      • Principal Investigator: Bao fu Chen, professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologic diagnosis of squamous cell thoracic esophageal carcinoma of Stage IIB or III, which is potentially resectable.
2. Patients must not have received any prior anticancer therapy.
3. More than 6 months of expected survival.
4. Age ranges from 18 to 70 years.
5. Absolute white blood cells count ≥4.0×109/L, neutrophil ≥1.5×109/L, platelets ≥100.0×109/L, hemoglobin ≥90g/L, and normal functions of liver and kidney.
6. Karnofsky performance status (KPS) of 90 or more.
7. Signed informed consent document on file.

Exclusion Criteria:

1. Patients are diagnosed or suspected to be allergic to cisplatin or vinorelbine.
2. Patients with concomitant hemorrhagic disease.
3. Pregnant or breast feeding.
4. Inability to use gastric conduit after esophagectomy because of a prior surgery.
5. Patients with concomitant peripheral neuropathy, whose CTC status is 2 or even more.
6. Have a prior malignancy other than esophageal carcinoma, carcinoma in situ of the cervix, nonmelanoma skin cancer or cured early stage of prostate cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: experimental group; Neo-adjuvant Chemoradiotherapy followed by Mckeown MIE	Procedure: Neo-adjuvant Chemoradiotherapy followed by Mckeown MIE; Neo-adjuvant Chemoradiotherapy followed by Mckeown MIE
ACTIVE_COMPARATOR: Radical Chemoradiotherapy; only Radical Chemoradiotherapy	Drug: Cisplatin; only Radical Chemoradiotherapy; Other Names: vinorelbine
ACTIVE_COMPARATOR: Mckeown MIE; only Mckeown MIE	Device: Mckeown MIE; only Mckeown MIE using thoracoscopy and laparoscopy; Other Names: Laparoscopy; Thoracoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival rate	1 years
Disease free survival	5years
Overall survival rate	3years
Overall survival rate	5years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the opportunity of MIE after neo-adjuvant chemoradiotherapy	Criteria:Response Evaluation Criteria in Solid Tumors，RECIST	4 weeks after completion of radiotherapy
Side effects of neo-adjuvant chemoradiotherapy	Evaluate the toxicities of neo-adjuvant chemoradiotherapy,according to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 3.0	2 weeks after completion of radiotherapy
Duration of surgery	The time between the start of surgery until the end of surgery	Intraoperative
Quantity of bleeding	The amount of bleeding during surgery	Intraoperative
number of lymph nodes retrieved	The total number of lymph nodes obtained including cervix area, mediastinum area , abdominal area	Intraoperative
Days of postoperative stay	Participants will be followed for the duration of hospital stay after surgery, an expected average of 12 days	The duration of hospital stay after surgery, an expected average of 12 days
Rate of Operative Complication		30 days after surgery
Mortality of perioperation		30 days after surgery

Collaborators and Investigators

• Sponsor: Chengchu Zhu
• Collaborators: Sun Yat-sen University; Fudan University
• Investigators: Study Chair: Cheng chu Zhu, professor, Taizhou Hospital; Study Director: Bao fu Chen, professor, Taizhou Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (ANTICIPATED): June 1, 2015
• Study Completion (ANTICIPATED): July 1, 2019

Study Registration Dates

• First Submitted: June 28, 2014
• First Submitted That Met QC Criteria: July 9, 2014
• First Posted (ESTIMATE): July 11, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): July 11, 2014
• Last Update Submitted That Met QC Criteria: July 9, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: laparoscopy; thoracoscopy; minimally invasive esophagectomy; Squamous Cell Esophageal Carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Carcinoma; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Cisplatin; Vinorelbine
• Other Study ID Numbers: BZhang; 2011C13039-2 (OTHER_GRANT: Zhejiang Provincial Science and Technology Major Projects)