Neoadjuvant Chemotherapy Versus Surgery Alone for Esophageal Squamous Cell Carcinoma

A Phase III, Multicenter Randomized Controlled Study of Neo-adjuvant Chemotherapy Paclitaxel + Cisplatin Versus Surgery Alone for Stage IIA-IIIB Esophageal Squamous Cell Carcinoma

The effect of neo-adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas remains the most controversial part of neo-adjuvant therapy for esophageal carcinomas. One of our objectives is to evaluate whether the neo-adjuvant therapy with cisplatin and paclitaxel followed by right thoracic approach esophagectomy with total 2-field lymph node dissection improves the overall survival of thoracic esophageal cancer patients.

Study Overview

• Status: Completed
• Conditions: Esophageal Neoplasm
• Intervention / Treatment: Drug: cisplatin and paclitaxel

Detailed Description

The effect of Neo-adjuvant chemotherapy on survival of patients with thoracic esophageal squamous cell carcinomas remains the most controversial part of Neo-adjuvant therapy for esophageal carcinomas. Therefore, the optimal management of resectable esophageal squamous cell carcinomas differs widely among different areas based on local randomized controlled trials.

The neo-adjuvant chemotherapy might be a good strategy if sufficient local control is achieved by surgical treatment. This study defined the detail of surgery procedure and the region of lymphadenectomy and adopted cisplatin and paclitaxel as neoadjuvant chemotherapy regimens. We try to evaluate the efficacy and safety of this neo-adjuvant strategy.

• Study Type: Interventional
• Enrollment (Anticipated): 528
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100029
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  • Fujian
    • FuZhou, Fujian, China
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen Uniersity Cancer Center
  • Henan
    • Anyang, Henan, China
      • Anyang Cancer Hospital
    • ZhengZhou, Henan, China, 450008
      • Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Province Tumor Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan Universitay Shanghai Cancer Center
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 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 IIA to IIIB, (7th Union for International Cancer Control, UICC-TNM).
2. Patients must not have received any prior anticancer therapy of esophageal carcinoma.
3. Age ranges from 18 to 75 years.
4. Without operative contraindication.
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, total bilirubin（TBIL）≤1.5N, aspartate aminotransferase (AST)≤2.5N, alanine aminotransferase(ALT)≤2.5N, prothrombin time(PT)≤1.5N, and activated partial thromboplastin time(APTT) is in normal range, endogenous creatinine clearance rate(CRE)≤1.5N.
6. Patients must not have diagnosed with other cancer and must not received any prior anticancer therapy except prostatic cancer with more than 5 years disease-free survival(DFS).
7. expected R0 resection.
8. ECOG 0～2.
9. Signed informed consent document on file. 10.No metastatic lymph node in cervical by color doppler sonography.

Exclusion Criteria:

1. Multiple primary cancer.
2. The subject cannot understand and sign the informed consent form(ICF).
3. Patients with concomitant hemorrhagic disease.
4. Any un expected reason for patients can't get operation.
5. Inability to use gastric conduit after esophagectomy because of a prior surgery.
6. Pregnant or breast feeding.
7. Patients are diagnosed or suspected to be allergic to cisplatin or Paclitaxel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neo-adjuvant chemotherapy group; Neo-adjuvant chemotherapy(cisplatin and paclitaxel): Paclitaxel, 175mg/m2, d1, Cisplatin, 25mg/m2, d2-d4, 3 week, 2 cycles.; Paclitaxel, 87.5mg/m2, d1,d8, Cisplatin, 25mg/m2, d2-d4, 3 week, 2 cycles.; Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles. Surgery: 2-3weeks after Neo-adjuvant chemotherapy; Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality.; Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included).	Drug: cisplatin and paclitaxel; Paclitaxel, 175mg/m2, d1, Cisplatin, 25mg/m2, d2-d4, 3 week, 2 cycles.; Paclitaxel, 87.5mg/m2, d1,d8, Cisplatin, 25mg/m2, d2-d4, 3 week, 2 cycles.; Paclitaxel, 175mg/m2, d1, Cisplatin, 75mg/m2, d1, 3 week, 2 cycles.; Other Names: TP
No Intervention: Surgery alone group; Surgery: 2-3weeks after Neo-adjuvant chemotherapy; Surgeons: the operation shall be performed by senior thoracic surgeons. Try to achieve the consistency of operation quality.; Operation: the thoracic esophagectomy must be through right thoracic cavity. (open and minimally invasive McKeown or Ivor Lewis). Total two-field lymphadenectomy (right and left recurrent laryngeal nerve lymph nodes must be included).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival rate	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival		5 years
Overall survival rate		1 years and 3 years
assessment in perioperation-Removal rate (R0 resection rate)	The R0 resection rate of two groups	perioperative period
assessment in perioperation-Rate of Operative Complication	Complication rate after operation before discharge	perioperative period
assessment in perioperation-Mortality of perioperation	Mortality of perioperation 20 days before operation and 30 days after operation	perioperative period
assessment in perioperation-Days of Hospitalization	Days of Hospitalization after operation	perioperative period
assessment in perioperation-Thoracic Drainage	Thoracic Drainage days	perioperative period
assessment in perioperation-Quantity of bleeding	blood lose during operation	perioperative period
assessment in perioperation-Time of operation	the time from open thoracic cavity to the closure of the thoracic cavity	perioperative period
Quality of life	ECOG, KPS, NRS-2002, EORTC QLQ-ST018, EORTC QLQ-C30	1 years
efficacy of neo-adjuvant chemotherapy--response rate	Criteria:Response Evaluation Criteria in Solid Tumors，RECIST. Pathologic Complete Response Rate. Pathologic Response Rate.	1-4 days before operation
toxicities of neo-adjuvant chemotherapy	According to National Cancer Institute Common Terminology Criteria for Adverse Event,Version 3.0(CTC AE3.0). The complete rate of protocol	from chemotherapy to perioperative period
prognostic factors	prognostic factors for overall survival of both groups	5 years
predictive factors	predictive factors for the efficiency of neo-adjuvant chemotherapy	2 years

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Collaborators: Sun Yat-sen University; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Peking University Cancer Hospital & Institute; Tianjin Medical University Cancer Institute and Hospital; Hunan Province Tumor Hospital
• Investigators: Principal Investigator: Yin Li, MD.&PhD., The Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital)

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): October 1, 2022

Study Registration Dates

• First Submitted: February 26, 2015
• First Submitted That Met QC Criteria: March 23, 2015
• First Posted (Estimate): March 24, 2015

Study Record Updates

• Last Update Posted (Actual): October 5, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin
• Other Study ID Numbers: Henan CH