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Perioperative Chemotherapy Plus Toripalimab for Epstein-Barr Virus-associated Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma

Primary Purpose

Adenocarcinoma of the Stomach, Adenocarcinoma of Esophagogastric Junction, Epstein-Barr Virus-Associated Gastric Carcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Toripalimab
Oxaliplatin
S1
Sponsored by
Yu jiren
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenocarcinoma of the Stomach focused on measuring Gastric Adenocarcinoma, Esophagogastric Junction Adenocarcinoma, Perioperative Chemotherapy, Toripalimab, Epstein-Barr Virus-associated gastric cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Voluntary participation in the clinical study; fully understands and is informed of the study and has signed the Informed Consent Form (ICF). Participants were ambulatory male or female. Age: ≥ 18 years and ≤ 80 years old. Histopathologically confirmed gastric or esophagogastric junction adenocarcinoma. Epstein-Barr Virus-associated Gastric or Esophagogastric Junction Adenocarcinoma, which was determined by in situ hybridization (ISH) test of endoscopic biopsy specimen. cT2-4bN+/-, M0 according to the American Joint Committee on Cancer and Union for International Cancer Control (AJCC-UICC) TNM classification for carcinoma of the stomach (8th edition). Participants had Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 within 7 days before the first dose of study treatment. Life expectancy ≥ 6 months. Agreement of providing baseline and surgical specimens for biomarker analysis. The functions of the vital organs meet requirements as follows (within 14 days before the first dose of study treatment, meanwhile, participants had not received treatment of recombinant human thrombopoietin or granulocyte stimulating factor): 1). Hematological function White blood cell count (WBC): 3.5 × 10^9/L ~12.0 × 10^9/L Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L Platelet count (PLT) ≥ 100 × 10^9/L Hemoglobin (Hb) ≥ 90g/L. 2). Hepatic function Total bilirubin (TBIL) ≤ 1.5 × ULN (upper limit of normal); -Aspartate aminotransferase (AST) ≤ 2.5 × ULN; Alanine aminotransferase (ALT) ≤ 2.5 × ULN; Albumin (ALB) ≥ 30g/L. 3). Renal function Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 60 ml/min for those with creatinine level > 1.5 × ULN. 4). Coagulation function International normalized ratio (INR) ≤ 1.5; Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. 10. Female participants of childbearing age must meet requirements: urine or serum pregnancy test must be negative within 7 days before the first dose of study treatment, and she must agree to use adequate contraception methods or keep abstinence (starting with the ICF is signed through 120 days after the last dose of toripalimab, or 180 days after the last dose of chemotherapy, whichever is longer, and should not be breastfeeding. Male participants must meet requirements: agree to use adequate contraception methods or keep abstinence (starting with the ICF is signed through 120 days after the last dose of toripalimab, or 180 days after the last dose of chemotherapy, whichever is longer). Exclusion Criteria: HER2-positive status defined as either IHC score of 3+ or IHC 2+ with amplification proven by fluorescent in situ hybridization (FISH) based on pretreatment endoscopic biopsies. Prior systemic therapy for treatment of gastric cancer (surgery, chemotherapy, radiotherapy, targeted therapy or immunotherapy). Previous or concurrent have other active malignant tumors within the past 5 years (except for basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate cancer or cervical cancer or breast cancer in situ that has undergone curative therapy). Participants with gastric outlet obstruction, or unable to oral take, or severe gastrointestinal bleeding. Myocardial infarction within 6 months before the first dose of study treatment, uncontrolled angina, arrhythmia which need medical intervention (including but not limited to cardiac pacemaker), congestive heart failure (New York Heart Association (NYHA) class III or IV). Existence of chronic diarrhea (watery diarrhea: ≥ 5 times per day). Participants with active infection within 14 days before the first dose of study treatment which need medical intervention. Participants with active tuberculosis. Previous or concurrent diagnosed with interstitial lung disease by imaging or symptoms. Any of the following test is positive: Human Immunodeficiency Virus (HIV) antibody, Hepatitis B surface Antigen (HBsAg), or Hepatitis C Virus (HCV) antibody. Participants who need long-term systemic steroid therapy (> 10 mg/d prednisone equivalent) or any other form of immunosuppressive therapy within 14 days before the first dose of study treatment or during the study period. Concurrent or previous have severe allergic reaction to any antibody based drugs. Existence of any concurrent autoimmune disease, excepting participants with diabetes mellitus type I, hypothyroidism requiring only hormone replacement therapy. Receive live vaccines within 28 days before the first dose of study treatment or during the study period, excepting inactivated viral vaccines for seasonal influenza. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. Existence of systemic disease that is difficult to control despite treatment with several agents, for example, diabetes mellitus, hypertension, etc. Existence of other serious physical or mental diseases or serious laboratory abnormalities that may increase the risk of participating in the study. Participants who were judged unsuitable as subjects of this trial by investigator.

Sites / Locations

  • The First Affiliated Hospital, College of Medicine, Zhejiang University
  • The Second Affiliated Hospital, College of Medicine, Zhejiang University
  • Huzhou Central Hospital
  • Lishui Central Hospital
  • Ningbo First Hospital
  • Ningbo Medical Center LiHuiLi Hospital
  • Ningbo Second Hospital
  • Taizhou Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemotherapy+Toripalimab

Arm Description

Toripalimab: 240 mg IV infusion on Day 1 of each 21 day cycle for 3 cycles prior to surgery and 3 cycles after surgery. Chemotherapy: SOX(S-1+Oxaliplatin) Oxaliplatin,administered as a 2-hour intravenous infusion (130mg/m2) S-1, orally twice daily for 2 weeks followed by a 7-day rest period. The dose of S-1 was 80 mg/day for body surface area less than 1.25 m2, 100 mg/day for body surface area greater than or equal to 1.25 to less than 1.5 m2, and 120 mg/day for body surface area greater than or equal to 1.5 m2 Chemotherapy will be repeated each 21 day for 3 cycles prior to surgery and 3 cycles after surgery.

Outcomes

Primary Outcome Measures

Rate of pathological complete responses (pCR)
Percentage of patients with pCR referring to the total number of enrolled and eligible patients, as evaluated centrally by a reference pathologist.

Secondary Outcome Measures

Overall survival
The duration of overall survival (OS) will be determined by measuring the time interval from enrollment to the end of follow up or death from any cause
Progression-free survival
Progression-free survival (PFS) was defined as the time from randomization to the last follow-up or the time of disease progression or relapse or death from any cause.
The incidences and types of adverse events (AE) and severe adverse events (SAE)
The incidences and severity of adverse events that occur during treatment will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.3

Full Information

First Posted
July 25, 2023
Last Updated
July 25, 2023
Sponsor
Yu jiren
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1. Study Identification

Unique Protocol Identification Number
NCT05970627
Brief Title
Perioperative Chemotherapy Plus Toripalimab for Epstein-Barr Virus-associated Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma
Official Title
Perioperative Chemotherapy Combined With PD-1 Inhibitor (Toripalimab) for Treatment of Epstein-Barr Virus-associated Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma: a Prospective, Multi-center, Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 28, 2023 (Anticipated)
Primary Completion Date
July 28, 2026 (Anticipated)
Study Completion Date
July 28, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Yu jiren

4. Oversight

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

5. Study Description

Brief Summary
This study is a prospective, single arm, multi-center phase II clinical trial designed to evaluate the efficacy and safety of perioperative SOX combined with toripalimab in participants with Epstein-Barr Virus-associated locally advanced gastric or esophagogastric junction adenocarcinoma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of the Stomach, Adenocarcinoma of Esophagogastric Junction, Epstein-Barr Virus-Associated Gastric Carcinoma
Keywords
Gastric Adenocarcinoma, Esophagogastric Junction Adenocarcinoma, Perioperative Chemotherapy, Toripalimab, Epstein-Barr Virus-associated gastric cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy+Toripalimab
Arm Type
Experimental
Arm Description
Toripalimab: 240 mg IV infusion on Day 1 of each 21 day cycle for 3 cycles prior to surgery and 3 cycles after surgery. Chemotherapy: SOX(S-1+Oxaliplatin) Oxaliplatin,administered as a 2-hour intravenous infusion (130mg/m2) S-1, orally twice daily for 2 weeks followed by a 7-day rest period. The dose of S-1 was 80 mg/day for body surface area less than 1.25 m2, 100 mg/day for body surface area greater than or equal to 1.25 to less than 1.5 m2, and 120 mg/day for body surface area greater than or equal to 1.5 m2 Chemotherapy will be repeated each 21 day for 3 cycles prior to surgery and 3 cycles after surgery.
Intervention Type
Drug
Intervention Name(s)
Toripalimab
Intervention Description
Perioperative Toripalimab, 240 mg IV infusion
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Oxaliplatin (130 mg/m2) infusion as perioperative chemotherapy
Intervention Type
Drug
Intervention Name(s)
S1
Intervention Description
S-1 orally intake as perioperative chemotherapy
Primary Outcome Measure Information:
Title
Rate of pathological complete responses (pCR)
Description
Percentage of patients with pCR referring to the total number of enrolled and eligible patients, as evaluated centrally by a reference pathologist.
Time Frame
From enrollment to surgery after pre-operative treatment (up to approximately 36 months)
Secondary Outcome Measure Information:
Title
Overall survival
Description
The duration of overall survival (OS) will be determined by measuring the time interval from enrollment to the end of follow up or death from any cause
Time Frame
From randomization to the last follow-up or death from any cause (up to approximately 72 months)
Title
Progression-free survival
Description
Progression-free survival (PFS) was defined as the time from randomization to the last follow-up or the time of disease progression or relapse or death from any cause.
Time Frame
From randomization to the last follow-up or the time of disease progression or relapse or death from any cause (up to approximately 72 months)
Title
The incidences and types of adverse events (AE) and severe adverse events (SAE)
Description
The incidences and severity of adverse events that occur during treatment will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.3
Time Frame
From enrollment to 90-day after the last dose administration (up to approximately 39 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Voluntary participation in the clinical study; fully understands and is informed of the study and has signed the Informed Consent Form (ICF). Participants were ambulatory male or female. Age: ≥ 18 years and ≤ 80 years old. Histopathologically confirmed gastric or esophagogastric junction adenocarcinoma. Epstein-Barr Virus-associated Gastric or Esophagogastric Junction Adenocarcinoma, which was determined by in situ hybridization (ISH) test of endoscopic biopsy specimen. cT2-4bN+/-, M0 according to the American Joint Committee on Cancer and Union for International Cancer Control (AJCC-UICC) TNM classification for carcinoma of the stomach (8th edition). Participants had Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 within 7 days before the first dose of study treatment. Life expectancy ≥ 6 months. Agreement of providing baseline and surgical specimens for biomarker analysis. The functions of the vital organs meet requirements as follows (within 14 days before the first dose of study treatment, meanwhile, participants had not received treatment of recombinant human thrombopoietin or granulocyte stimulating factor): 1). Hematological function White blood cell count (WBC): 3.5 × 10^9/L ~12.0 × 10^9/L Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L Platelet count (PLT) ≥ 100 × 10^9/L Hemoglobin (Hb) ≥ 90g/L. 2). Hepatic function Total bilirubin (TBIL) ≤ 1.5 × ULN (upper limit of normal); -Aspartate aminotransferase (AST) ≤ 2.5 × ULN; Alanine aminotransferase (ALT) ≤ 2.5 × ULN; Albumin (ALB) ≥ 30g/L. 3). Renal function Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 60 ml/min for those with creatinine level > 1.5 × ULN. 4). Coagulation function International normalized ratio (INR) ≤ 1.5; Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. 10. Female participants of childbearing age must meet requirements: urine or serum pregnancy test must be negative within 7 days before the first dose of study treatment, and she must agree to use adequate contraception methods or keep abstinence (starting with the ICF is signed through 120 days after the last dose of toripalimab, or 180 days after the last dose of chemotherapy, whichever is longer, and should not be breastfeeding. Male participants must meet requirements: agree to use adequate contraception methods or keep abstinence (starting with the ICF is signed through 120 days after the last dose of toripalimab, or 180 days after the last dose of chemotherapy, whichever is longer). Exclusion Criteria: HER2-positive status defined as either IHC score of 3+ or IHC 2+ with amplification proven by fluorescent in situ hybridization (FISH) based on pretreatment endoscopic biopsies. Prior systemic therapy for treatment of gastric cancer (surgery, chemotherapy, radiotherapy, targeted therapy or immunotherapy). Previous or concurrent have other active malignant tumors within the past 5 years (except for basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate cancer or cervical cancer or breast cancer in situ that has undergone curative therapy). Participants with gastric outlet obstruction, or unable to oral take, or severe gastrointestinal bleeding. Myocardial infarction within 6 months before the first dose of study treatment, uncontrolled angina, arrhythmia which need medical intervention (including but not limited to cardiac pacemaker), congestive heart failure (New York Heart Association (NYHA) class III or IV). Existence of chronic diarrhea (watery diarrhea: ≥ 5 times per day). Participants with active infection within 14 days before the first dose of study treatment which need medical intervention. Participants with active tuberculosis. Previous or concurrent diagnosed with interstitial lung disease by imaging or symptoms. Any of the following test is positive: Human Immunodeficiency Virus (HIV) antibody, Hepatitis B surface Antigen (HBsAg), or Hepatitis C Virus (HCV) antibody. Participants who need long-term systemic steroid therapy (> 10 mg/d prednisone equivalent) or any other form of immunosuppressive therapy within 14 days before the first dose of study treatment or during the study period. Concurrent or previous have severe allergic reaction to any antibody based drugs. Existence of any concurrent autoimmune disease, excepting participants with diabetes mellitus type I, hypothyroidism requiring only hormone replacement therapy. Receive live vaccines within 28 days before the first dose of study treatment or during the study period, excepting inactivated viral vaccines for seasonal influenza. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. Existence of systemic disease that is difficult to control despite treatment with several agents, for example, diabetes mellitus, hypertension, etc. Existence of other serious physical or mental diseases or serious laboratory abnormalities that may increase the risk of participating in the study. Participants who were judged unsuitable as subjects of this trial by investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jiren Yu
Phone
0086-0571-87237931
Email
yujr0909@zju.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Kankai Zhu
Email
zhukankai0401@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jiren Yu
Organizational Affiliation
First Affiliated Hospital of Zhejiang University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital, College of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Name
The Second Affiliated Hospital, College of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian Chen
Facility Name
Huzhou Central Hospital
City
Huzhou
State/Province
Zhejiang
ZIP/Postal Code
313099
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yunhai Wei
Facility Name
Lishui Central Hospital
City
Lishui
State/Province
Zhejiang
ZIP/Postal Code
323000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongtao Xu
Facility Name
Ningbo First Hospital
City
Ningbo
State/Province
Zhejiang
ZIP/Postal Code
315010
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhilong Yan
Facility Name
Ningbo Medical Center LiHuiLi Hospital
City
Ningbo
State/Province
Zhejiang
ZIP/Postal Code
315048
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weiming Yu
Facility Name
Ningbo Second Hospital
City
Ningbo
State/Province
Zhejiang
ZIP/Postal Code
315099
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ping Chen
Facility Name
Taizhou Hospital
City
Taizhou
State/Province
Zhejiang
ZIP/Postal Code
317099
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shenkang Zhou

12. IPD Sharing Statement

Learn more about this trial

Perioperative Chemotherapy Plus Toripalimab for Epstein-Barr Virus-associated Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma

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