Clinical trial NCT03001596: Comparison Between NCRT and NCT Followed by MIE for Treatment of Locally Advanced Resectable ESCC
Official title: Neoadjuvant Chemoradiotherapy VS. Neoadjuvant Chemotherapy Followed by Minimally Invasive Esophagectomy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma（cT3-4aN0-1M0):A Multi-center Prospective Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Esophageal Squamous Cell Carcinoma Stage cT3-4aN0-1M0
Keywords: Neoadjuvant Chemoradiotherapy
Neoadjuvant Chemotherapy
Minimally Invasive Esophagectomy
Esophageal Squamous Cell Carcinoma（cT3-4aN0-1M0）
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Fujian Medical University Union Hospital
name: Tianjin Medical University Cancer Institute and Hospital
name: Ruijin Hospital
name: Shanghai Chest Hospital
name: First Affiliated Hospital of Chongqing Medical University
name: Changzhi Medical College
name: First Affiliated Hospital of Wenzhou Medical University
name: Wuhan Union Hospital, China
name: Peking University Cancer Hospital and Institute
First posted: 2016-12-23
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the outcomes of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy on patients with locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0).

Detailed description: It is a prospective randomized phase III clinical trial sponsored by Shanghai Zhongshan Hospital with other eight hospitals in China participating in. 264 patients with locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0) are recruited and randomly assigned into the neoadjuvant chemoradiotherapy group (NCRT group) and the neoadjuvant chemotherapy group (NCT group) according to the proportion of 1:1.The safety,efficacy of protocols and prognosis of patients are compared between the two regimens.

Eligibility criteria: Inclusion Criteria:

1. Histologically-confirmed squamous cell carcinoma of the esophagus;
2. Tumors of the esophagus are located in the thoracic cavity;
3. Pre-treatment stage as cT3-4aN0-1M0 (AJCC/UICC 7th Edition) (In case of stage cT4a, curative resectability has to be explicitly verified by the local surgical investigator prior to randomization).
4. Age is between 18 years and 75 years,
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
6. Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction \> 50 %.
7. Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests.
8. Adequate bone marrow function (White Blood Cells \>4x10\^9 /L; Neutrophil \>2.0×10\^9 /L; Hemoglobin \> 90 g/L; platelets\>100x10\^9 /L);
9. Adequate liver function (Total bilirubin \<1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) \<1.5x ULN);
10. Adequate renal function (Glomerular filtration rate (CCr) \>60 ml/min; serum creatinine (SCr) ≤120 µmol/L)；
11. The patient has provided written informed consent and is able to understand and comply with the study;

Exclusion Criteria:

1. Patients with non-squamous cell carcinoma histology;
2. Patients with advanced inoperable or metastatic esophageal cancer;
3. Pre-treatment stage as cT1-2N0-1M0 (AJCC/UICC 7th Edition);
4. Pre-treatment stage as cN2-3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 7th Edition);
5. Patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator.
6. Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder;
7. Pregnant or lactating women and fertile women who will not be using contraception during the trial;
8. Allergy to any drugs;
9. Participation in another intervention clinical trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent;
10. Expected lack of compliance with the protocol.

Primary outcomes:
measure: Overall survival(OS)
timeFrame: Up to the date of death of any causes since the date of randomization, up to 36 months
Secondary outcomes:
measure: Progression-free survival(PFS)
timeFrame: Up to the date of disease recurrence since the date of randomization, up to 36 months
measure: Pathological response rate(pCR)
timeFrame: Up to the date of pathological reports obtained since the date of randomization, up to 12 months
measure: R0 resection rate
timeFrame: Up to the date of pathological reports obtained since the date of randomization, up to 12 months
measure: Positive lymph nodes' number
timeFrame: Up to the date of pathological reports obtained since the date of randomization, up to 12 months
measure: Treatment related complications
timeFrame: Up to 1 month after surgery since the data of randomization, up to 13 months
measure: Quality of life(QOL)
timeFrame: Up to the end of follow-up since the data of surgery, up to 36 months
measure: Recurrence-free survival (RFS)
timeFrame: Up to the date of disease recurrence since the date of surgery, up to 36 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Lijie Tan, MD
role: STUDY_DIRECTOR
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