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

Yu jiren8 sites in 1 country30 target enrollmentJuly 28, 2023

Overview

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.

Registry

clinicaltrials.gov

Start Date

July 28, 2023

End Date

July 28, 2029

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Yu jiren

Responsible Party

Sponsor Investigator

Principal Investigator

Yu jiren

Director of gastrointestinal surgery department

First Affiliated Hospital of Zhejiang University

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):
•. Hematological function

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.

Arms & Interventions

Chemotherapy+Toripalimab

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: Toripalimab

Chemotherapy+Toripalimab

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: Oxaliplatin

Chemotherapy+Toripalimab

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: S1

Outcomes

Primary Outcomes

Rate of pathological complete responses (pCR)

Time Frame: From enrollment to surgery after pre-operative treatment (up to approximately 36 months)

Percentage of patients with pCR referring to the total number of enrolled and eligible patients, as evaluated centrally by a reference pathologist.

Secondary Outcomes

Overall survival(From randomization to the last follow-up or death from any cause (up to approximately 72 months))
Progression-free survival(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))
The incidences and types of adverse events (AE) and severe adverse events (SAE)(From enrollment to 90-day after the last dose administration (up to approximately 39 months))