Goal-directed Enteral Nutritional Perioperative Management (GENTLEMAN)

Goal-directed Enteral Nutritional Therapy for Malnourished Esophageal Cancer Patients During Perioperative Management

This clinical trial aims to determine whether perioperative goal-directed nutritional therapy can prevent postoperative pulmonary and other major complications in malnourished esophageal squamous cell cancer patients. Its main question is whether individualized nutritional therapy can improve short-term surgical outcomes and long-term prognosis. Researchers will compare goal-directed and conventional nutritional therapy to identify differences in morbidities and survival.

Study Overview

• Status: Recruiting
• Conditions: Esophagus Cancer
• Intervention / Treatment: Dietary supplement: Goal-directed EN therapy; Dietary supplement: Conventional EN therapy

Detailed Description

Severe malnutrition is a significant risk factor for postoperative complications in esophageal cancer patients. Early oral nutritional supplementation after surgery can prevent weight loss and improve quality of life. The EFFORT trial showed that individual-based enteral nutrition support reduced complications, extended 1-year survival, and improved quality of life. This study aims to assess the safety and effectiveness of individualized perioperative nutrition support guided by daily energy targets in esophageal cancer patients at nutritional risk. It also seeks to determine if supplementing immunonutrition can effectively reduce postoperative complications. This study was conducted as a multicenter, open-label, randomized, controlled phase 3 trial. The experiment group was administered goal-directed enteral nutritional therapy, while the control group received conventional enteral nutritional therapy. The study observed the participants' major pulmonary and other complications within 90 days post-surgery and nutritional status, disease-free survival (DFS), and overall survival (OS) in both groups.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaozheng Kang, M.D.; Phone Number: +86 13910052790; Email: kangxz@cicams.ac.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Yin Li, M.D.; Phone Number: +86 (010) 87788052; Email: liyin@cicams.ac.cn
  • Chongqing
    • Chongqing, Chongqing, China
      • Recruiting
      • Daping Hospital, Third Affiliated Hospital of Third Military Medical University
      • Contact: Wei Guo, M.D.
  • Fujian
    • Fuzhou, Fujian, China
      • Recruiting
      • Fujian Cancer Hospital
      • Contact: Shuoyan Liu, M.D.
  • Henan
    • Anyang, Henan, China
      • Recruiting
      • Anyang Cancer Hospital
      • Contact: Anlin Hao, M.D.
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Yan Zheng, M.D.
    • Zhengzhou, Henan, China
      • Recruiting
      • First Affiliated Hospital of Zhengzhou University
      • Contact: Xiangnan Li, M.D.
  • Jiangsu
    • Huai'an, Jiangsu, China
      • Recruiting
      • Huai'an first people's hospital
      • Contact: Jianqiang Zhao, M.D.
    • Nanjing, Jiangsu, China
      • Recruiting
      • Jiangsu Provincial People's Hospital
      • Contact: Jinhua Luo, M.D.
    • Nanjing, Jiangsu, China
      • Recruiting
      • Jiangsu Cancer Hospital
      • Contact: Feng Jiang, M.D.
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Lin Li, M.D.
    • Jinan, Shandong, China
      • Recruiting
      • Shandong Provincial Hospital
      • Contact: Lin Zhang, M.D.
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Zhongshan Hospital Affiliated to Fudan University
      • Contact: Lijie Tan, M.D.
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Chest Hospital
      • Contact: Zhigang Li, M.D.
  • Shanxi
    • Changzhi, Shanxi, China
      • Recruiting
      • Changzhi People's Hospital
      • Contact: Changhong Lian, M.D.
    • Taiyuan, Shanxi, China
      • Recruiting
      • Shanxi Cancer Hospital, Chinese Academy of Medical Sciences
      • Contact: Jianhong Lian, M.D.
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Medical University Cancer Institute & Hospital
      • Contact: Peng Tang, M.D.
  • Yunnan
    • Kunming, Yunnan, China
      • Recruiting
      • Yunnan Cancer Hospital
      • Contact: Guangqiang Zhao, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18-80 years old;
2. ECOG PS 0~1;
3. NRS 2002 score ≥3;
4. Malnutrition diagnosed according to the GLIM criteria;
5. Histopathologically confirmed as esophageal squamous cell carcinoma;
6. Primary tumors located in thoracic esophagus;
7. Resectable locally advanced disease with clinical stage II to IVA (8th edition UICC/AJCC) evaluated by a multidisciplinary team;
8. Neoadjuvant therapy will be administered, which may entail preoperative chemo-radiotherapy, chemotherapy only, or a combination of immunotherapy such as anti-PD-1/PD-L1;
9. Informed consent for random assignment and completion of the protocol.

Exclusion Criteria:

1. NRS 2002 score < 3;
2. Upfront surgery without neoadjuvant treatment;
3. Any comorbidity interferes with the digestion and absorption of ORAL IMPACT®;
4. Receiving any other nutritional support during the study;
5. Unable to consume nutrition orally or receive it through tube feeding before surgery;
6. History of other malignancies in the past 5 years, except successfully treated basal-cell skin carcinoma and cervical tumors in situ;
7. Severe abnormalities of liver and kidney functions (ALT≥2 times the upper limit of normal; Total bilirubin Tbil≥2 upper limit of normal; Creatinine Cr≥2 upper limit of normal);
8. Metabolic disorders, including uncontrolled diabetes mellitus or fasting blood glucose ≥10mmol/L, hypothyroidism, or hyperthyroidism;
9. Receiving fat emulsion containing Omega-3 fatty acids, glutamine, thymosin, glucocorticoid, thyroxine, growth hormone, and anti-tumor necrosis factor biologic agents
10. History of known allergy to any component of ORAL IMPACT®;
11. Pregnant or lactating women, women of childbearing potential with either a positive pregnancy test at baseline or not using a reliable and appropriate contraceptive method;
12. Refuse to sign the consent or unable to follow the study protocol;
13. Inappropriate to participate in this study judged by investigators.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Goal-directed enteral nutritional therapy; The participants will be administered a supervised goal-directed nutritional therapy. The enteral nutrition (EN) regimens include homemade meals with or without ORAL IMPACT® according to the daily goal.	Dietary supplement: Goal-directed EN therapy; The participants will be administered a supervised goal-directed nutritional therapy. The enteral nutrition (EN) regimens include homemade meals with or without ORAL IMPACT® according to the daily goal.
Active Comparator: Conventional enteral nutritional therapy; The participants will be administered with an unsupervised and liberal nutritional support. The EN regimens will not include ORAL IMPACT®.	Dietary supplement: Conventional EN therapy; The participants will be administered the conventional nutritional therapy according to the Chinese expert consensus on perioperative nutritional support in enhanced recovery after surgery (2019 edition).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of postoperative pulmonary complications	According to the Esophagectomy Complications Consensus Group (ECCG) standardization of complications reporting, pulmonary complications include pneumonia, pleural effusion, pneumothorax, atelectasis, mucous plugging, respiratory failure, acute respiratory distress syndrome, acute aspiration, tracheobronchial injury, and prolonged air-leak.	Randomization to three months after surgery
Rate of unplanned hospital admissions	Any admission (all cause) for an unforeseen or unplanned (non-elective) cause within 90 days of discharge from an index acute hospital admission.	Randomization to three months after surgery
Rate of unplanned ICU admission	Any admission (all cause) for an unforeseen or unplanned (non-elective) cause within 90 days of discharge from an index acute ICU admission.	Randomization to three months after surgery
Overall survival	The time from randomization to death. Any patients lost to follow up or still alive at the time of evaluation are censored.	Randomization to five years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of postoperative non-pulmonary complications	Non-pulmonary complications according to the ECCG standardization of complications reporting.	Randomization to three months after surgery
Level of serum prealbumin	Prealbumin, also known as transthyretin, has a half-life in plasma of ∼2 days, much shorter than that of albumin. Prealbumin is therefore more sensitive to changes in protein-energy status than albumin, and its concentration closely reflects recent dietary intake rather than overall nutritional status.	Randomization to three months after surgery
Body mass index (BMI)	A person's weight in kilograms divided by the square of height in meters.	Randomization to three months after surgery
Lean body mass	The weight of the body minus the⁣ fat content, representing the amount of⁣ muscle, bone, and organs in the body.	Randomization to three months after surgery
Rate of treatment-related adverse events (TRAEs)	An event that emerges during treatment having been absent pre-treatment, or worsens relative to the pre-treatment state.	Randomization to three months after surgery
Rate of R0 resection	Distance between tumor and the circumferential resection margin (CRM) more than 1 mm.	Randomization to three months after surgery
Rate of pathologic complete response (pCR)	The absence of invasive/in situ cancer in the resected esophagus and regional lymph nodes.	Randomization to three months after surgery
Disease-free survival (DFS)	Defined as the proportion of patients without disease progression or death.	Randomization to five years
Scale of health-related quality of life (HRQOL)	A state of complete physical, mental and social well-being, and not merely the absence of disease and infirmity evaluated by EORTC OES18、EQ-5D、FAACT.	Randomization to three months after surgery

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Yin Li, M.D., Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): May 30, 2031

Study Registration Dates

• First Submitted: June 18, 2024
• First Submitted That Met QC Criteria: July 14, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 14, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Survival; Morbidity; Esophageal Cancer; Esophagectomy; Malnourished; Nutritional Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms
• Other Study ID Numbers: GENTLEMAN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No