Clinical trial NCT04513418: Effects of Preoperative Enteral Immunonutrition for Esophageal Cancer Patients Given Neoadjuvant Chemoradiotherapy
Official title: Effects of Preoperative Enteral Immunonutrition for Esophageal Cancer Patients Given Neoadjuvant Chemoradiotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Esophageal Neoplasms
Keywords: Esophageal Neoplasms
Neoadjuvant Therapy
Enteral Nutrition
Nutrition Therapy
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Chest Hospital
name: Shanghai Zhongshan Hospital
name: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
name: Ningbo Medical Center Lihuili Hospital
name: Zhejiang Cancer Hospital
First posted: 2020-08-14
Enrollment: 244
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: SUPPORTIVE_CARE

Brief summary: This randomized controlled trial will evaluate the effects of preoperative enteral immunonutrition in esophageal cancer patients undergoing neoadjuvant therapy. The purpose of this study is to determine whether preoperative immune-modulating diet before surgery can improve the rate of complications and other perioperative outcomes.

Detailed description: Esophageal cancer ranks the fourth in mortality and the sixth in incidence among cancers in China according to the latest report of cancer epidemiology. Although the development of neoadjuvant therapy and radical esophagectomy have improved the prognosis of esophageal cancer patients, dysphagia and digestive tract reconstruction can cause malnutrition and infection-related complications. Postoperative enteral and parenteral nutrition have proved to be effective in improving outcomes after esophagectomy. However, whether to provide a preoperative nutritional support for patients with resectable esophageal cancer remains controversial.

This prospective randomized controlled trial will evaluate the effects of preoperative enteral immunonutrition in esophageal cancer patients undergoing neoadjuvant therapy. The purpose of this study is to determine whether preoperative immune-modulating diet before surgery can improve the rate of complications and other perioperative outcomes.

The sample size is estimated with the hypothesis that preoperative immunonutrition during the neoadjuvant therapy can reduce postoperative nutrition and immune-related complications after esophagectomy. According to the previously published articles, the required sample size of interventional and control arm (ratio=2:1) was calculated as 137 cases and 69 cases to detect the reduction in related complications from 50% to 30% based on a bilateral significance level (α) of 0.05 and a power of test (1-β) of 0.80. Considering an estimated drop rate of 15%, the minimum sample size of this study is 244 patients, 162 cases in the interventional group and 82 in the control group. After signing the informed consent, every eligible participant will be randomized into either group based on a computer-generated random number. Blinding will not be applied to patients and surgeons due to the difficulty in clinical practice but outcomes assessor will be masked.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed esophageal cancer
* Staging as cT2N0M0 with high-risk lesions (lymphovascular invasion, ≥3cm, poorly differentiated) / cT1b-2N+M0 / cT3-4aN0-3M0 with the need of neoadjuvant therapy before radical esophagectomy
* Tolerance with oral intake (at least fluid diet)
* Eastern Cooperative Oncology Group (ECOG) performance status ≤2
* Body Mass Index (BMI) ≥ 18.5 kg/m2 before recruitment
* Patient's approval and written informed consent

Exclusion Criteria:

* Expected survival time less than 6 months
* Complete dysphagia
* Pregnant or breast-feeding women
* Unable to obey the interventions because of any reasons
* Serious co-morbidities (cardiac, pulmonary, liver, kidney, brain, hematologic, endocrine and other diseases) in patients who cannot tolerate neoadjuvant therapy and/or surgery
* History of previous thoracic or abdominal surgery
* History of other malignant tumor (previous or current)
* Patients with primary small cell carcinoma of the esophagus

Primary outcomes:
measure: Rate of postoperative nutrition and immune-related complications
timeFrame: Up to 30 days after surgery
Secondary outcomes:
measure: Completion rate of neoadjuvant therapy and esophagectomy
timeFrame: 2-3 months before surgery
measure: Adverse events during neoadjuvant chemoradiotherapy
timeFrame: 2-3 months before surgery
measure: Pathological complete response rate (pCR)
timeFrame: 2-3 months before surgery
measure: Blood loss
timeFrame: At operation day
measure: Duration of surgery
timeFrame: At operation day
measure: Rate of surgery-related complications
timeFrame: At operation day
measure: Length of hospital stay
timeFrame: Postoperative in-hospital stay
measure: Hospitalization costs
timeFrame: Postoperative in-hospital stay
measure: 30-day and 90-day mortality
timeFrame: Up to 90 days after surgery
measure: Weight loss
timeFrame: From neoadjuvant chemoradiotherapy to 6 months after surgery
measure: Change in PG-SGA score after surgery
timeFrame: From neoadjuvant chemoradiotherapy to 6 months after surgery
measure: Change in biochemical indicators after surgery
timeFrame: From neoadjuvant chemoradiotherapy to 6 months after surgery
measure: Score of EORTC QLQ-C30 and OES-18 scale
timeFrame: 1-year, 3-year, and 5-year after surgery
measure: Long-term survival
timeFrame: 1-year, 3-year, and 5-year after surgery
Other outcomes:
measure: Minimal residual disease (MRD)
timeFrame: Before and after neoadjuvant chemoradiotherapy, 7-14 days after surgery
measure: Microbiomics analysis
timeFrame: 1 week before neoadjuvant chemoradiotherapy, 2-3 days before surgery
measure: Metabolomic analysis
timeFrame: 1 week before neoadjuvant chemoradiotherapy, 2-3 days before surgery
Locations:
city: Shanghai
country: China
facility: Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital Affiliated to Fudan University
state: Shanghai
city: Hangzhou
country: China
facility: Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Hospital
state: Zhejiang
Study officials:
affiliation: Ruijin Hospital
name: Hecheng Li, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cao Y, Han D, Yang S, Shi Y, Zhao S, Jin Q, Li J, Li C, Zhang Y, Shen W, He J, Wang M, Ji G, Li Z, He Y, Chen Q, Wei W, Chen C, Gong X, Wang J, Tan L, Wang H, Li H. Effects of pre-operative enteral immunonutrition for esophageal cancer patients treated with neoadjuvant chemoradiotherapy: protocol for a multicenter randomized controlled trial (point trial, pre-operative immunonutrition therapy). BMC Cancer. 2022 Jun 13;22(1):650. doi: 10.1186/s12885-022-09721-y.