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

Primary Purpose

Esophageal Squamous Cell Carcinoma, Intestinal Flora

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
SintilimabCombined With Chemotherapy
Sponsored by
The First Affiliated Hospital of Soochow University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional screening trial for Esophageal Squamous Cell Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • The first affiliated hospital of soochow universityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Sintilimab

Arm Description

Sintilimab Combined With Chemotherapy

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
December 13, 2021
Last Updated
January 5, 2022
Sponsor
The First Affiliated Hospital of Soochow University
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1. Study Identification

Unique Protocol Identification Number
NCT05199649
Brief Title
Correlation Between the Efficacy of Neoadjuvant Chemotherapy Combined With Immunotherapy of Operable Thoracic Esophageal Squamous Cell Carcinoma and the Metabolites of Intestinal Flora
Official Title
Correlation Between the Efficacy of Neoadjuvant Chemotherapy Combined With Immunotherapy of Operable Thoracic Esophageal Squamous Cell Carcinoma and the Metabolites of Intestinal Flora
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2021 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
June 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The First Affiliated Hospital of Soochow University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma, Intestinal Flora

7. Study Design

Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm Sintilimab
Arm Type
Experimental
Arm Description
Sintilimab Combined With Chemotherapy
Intervention Type
Drug
Intervention Name(s)
SintilimabCombined With Chemotherapy
Intervention Description
Sintilimab and chemotherapy are carried out at the same time for every 3 weeks
Primary Outcome Measure Information:
Title
Species and abundance of gut microbiota
Description
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.
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Explore the changes of intestinal flora and metabolomics before and after medication
Description
Discovery of gut microbes and metabolic markers that can predict the efficacy of chemotherapy combined with neoadjuvant immunotherapy for esophageal squamous cell carcinoma
Time Frame
2 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Refuse to participate; 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; 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; 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; 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; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Zhao
Phone
86-0512-67972216
Email
zhaojia0327@126.com
Facility Information:
Facility Name
The first affiliated hospital of soochow university
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jun Zhao
Phone
86-0512-67972216
Email
zhaojia0327@126.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32076145
Citation
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.
Results Reference
result
PubMed Identifier
20068171
Citation
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.
Results Reference
result
PubMed Identifier
32792462
Citation
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.
Results Reference
result
PubMed Identifier
32887946
Citation
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.
Results Reference
result
PubMed Identifier
31851298
Citation
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.
Results Reference
result

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

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