Correlation Between the Efficacy of Neoadjuvant Chemotherapy Combined With Immunotherapy of Operable Thoracic Esophageal Squamous Cell Carcinoma and the Metabolites of Intestinal Flora

This study collects stool, blood, and tumor tissue samples from patients with locally advanced esophageal cancer after receiving Sintilimab and chemotherapy to explore the efficacy and intestinal microbes of chemotherapy combined with neoadjuvant immunotherapy for locally advanced operable thoracic esophageal squamous cell carcinoma The main purpose is the relationship between its metabolites, and it will also explore the changes of intestinal flora diversity and metabolites before and after esophageal squamous cell carcinoma chemotherapy combined with immune neoadjuvant therapy

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma; Intestinal Flora
• Intervention / Treatment: Drug: SintilimabCombined With Chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jun Zhao; Phone Number: 86-0512-67972216; Email: zhaojia0327@126.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital Of Soochow University
      • Contact: Jun Zhao; Phone Number: 86-0512-67972216; Email: zhaojia0327@126.com

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) Age ≥18 years old and ≤75 years old; 2) Patients with stage I~III thoracic esophageal squamous cell carcinoma diagnosed by histopathological examination (excluding mixed adenosquamous carcinoma and other pathological types); 3) ECOG PS score is 0 or 1; 4) It has sufficient organ and bone marrow function.

Exclusion Criteria:

1. Refuse to participate;
2. Patients who have a higher risk of bleeding or perforation due to the tumor's obvious invasion of the adjacent organs (aorta or trachea) of the esophageal lesion, or patients who have formed a fistula;
3. Have previously received anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibody therapy, or any other antibodies targeting T cell costimulation or checkpoint pathways as specific targets or drug;
4. Participate in another interventional clinical study at the same time, unless participating in an observational (non-interventional) clinical study or in the follow-up phase of an interventional study;
5. Have received systemic systemic treatment with anti-tumor indications Chinese herbal medicine or immunomodulatory drugs (including thymosin, interferon, interleukin, etc.) within 2 weeks before the first administration;
6. Have used immunosuppressive drugs within 1 week before enrollment, excluding nasal spray, inhalation or other local glucocorticoids or physiological doses of systemic glucocorticoids (ie no more than 10mg/day prednisone Or equivalent doses of other glucocorticoids), or use hormones to prevent allergy to contrast agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm Sintilimab; Sintilimab Combined With Chemotherapy	Drug: SintilimabCombined With Chemotherapy; Sintilimab and chemotherapy are carried out at the same time for every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Species and abundance of gut microbiota	Alpha-diversity of samples, that measures both the richness and diversity of species within a group, was calculated on taxa that were observed at least once. Beta-diversity, that measures the differences in microbiome composition between groups.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explore the changes of intestinal flora and metabolomics before and after medication	Discovery of gut microbes and metabolic markers that can predict the efficacy of chemotherapy combined with neoadjuvant immunotherapy for esophageal squamous cell carcinoma	2 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Publications and helpful links

General Publications

• Lavelle A, Sokol H. Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020 Apr;17(4):223-237. doi: 10.1038/s41575-019-0258-z. Epub 2020 Feb 19.
• Wilson AJ, Chueh AC, Togel L, Corner GA, Ahmed N, Goel S, Byun DS, Nasser S, Houston MA, Jhawer M, Smartt HJ, Murray LB, Nicholas C, Heerdt BG, Arango D, Augenlicht LH, Mariadason JM. Apoptotic sensitivity of colon cancer cells to histone deacetylase inhibitors is mediated by an Sp1/Sp3-activated transcriptional program involving immediate-early gene induction. Cancer Res. 2010 Jan 15;70(2):609-20. doi: 10.1158/0008-5472.CAN-09-2327. Epub 2010 Jan 12.
• Mager LF, Burkhard R, Pett N, Cooke NCA, Brown K, Ramay H, Paik S, Stagg J, Groves RA, Gallo M, Lewis IA, Geuking MB, McCoy KD. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science. 2020 Sep 18;369(6510):1481-1489. doi: 10.1126/science.abc3421. Epub 2020 Aug 13.
• Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021 Jan;19(1):55-71. doi: 10.1038/s41579-020-0433-9. Epub 2020 Sep 4. Review.
• Ocvirk S, Wilson AS, Posma JM, Li JV, Koller KR, Day GM, Flanagan CA, Otto JE, Sacco PE, Sacco FD, Sapp FR, Wilson AS, Newton K, Brouard F, DeLany JP, Behnning M, Appolonia CN, Soni D, Bhatti F, Methe B, Fitch A, Morris A, Gaskins HR, Kinross J, Nicholson JK, Thomas TK, O'Keefe SJD. A prospective cohort analysis of gut microbial co-metabolism in Alaska Native and rural African people at high and low risk of colorectal cancer. Am J Clin Nutr. 2020 Feb 1;111(2):406-419. doi: 10.1093/ajcn/nqz301.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: January 5, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Actual): January 20, 2022
• Last Update Submitted That Met QC Criteria: January 5, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• 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; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma
• Other Study ID Numbers: 20211211

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