Perioperative Chemotherapy Plus Toripalimab for dMMR Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma

NCT05729646 | Recruiting Phase 2

• 1 other identifier: IIT20220083C-R1
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 8

Brief Summary

This study is a prospective, multi-center, randomized controlled phase II trial to compare the efficacy of perioperative SOX plus toripalimab, toripalimab monotherapy with SOX regimen in participants with dMMR locally advanced gastric or esophagogastric junction adenocarcinoma

Conditions

Adenocarcinoma of the Stomach; Adenocarcinoma of Esophagogastric Junction; Mismatch Repair Deficiency

Keywords

Gastric Adenocarcinoma; Esophagogastric Junction Adenocarcinoma; Perioperative Chemotherapy; Toripalimab

Outcome Measures

Primary Outcomes (1)

• Rate of major pathological response (MPR)

  Percentage of patients with MPR referring to the total number of patients with surgery, as evaluated centrally by a reference pathologist.

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

Secondary Outcomes (3)

• 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)

Study Arms (3)

Arm A (Chemotherapy+Toripalimab)

EXPERIMENTAL

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 (130 mg/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.

Drug: Toripalimab; Drug: Oxaliplatin; Drug: S1

Arm B (Toripalimab monotherapy)

EXPERIMENTAL

Toripalimab, 240 mg IV infusion on Day 1 of each 21 day cycle for 3 cycles prior to surgery and 3 cycles after surgery.

Drug: Toripalimab

Arm C (Chemotherapy)

ACTIVE COMPARATOR

Chemotherapy: SOX(S-1+Oxaliplatin) Oxaliplatin, administered as a 2-hour intravenous infusion (130 mg/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.

Drug: Oxaliplatin; Drug: S1

Interventions

Toripalimab DRUG

Perioperative Toripalimab, 240 mg IV infusion

Arm A (Chemotherapy+Toripalimab); Arm B (Toripalimab monotherapy)

Oxaliplatin DRUG

Oxaliplatin (130 mg/m2) infusion as perioperative chemotherapy

Arm A (Chemotherapy+Toripalimab); Arm C (Chemotherapy)

S1 DRUG

S-1 orally intake as perioperative chemotherapy

Arm A (Chemotherapy+Toripalimab); Arm C (Chemotherapy)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Mismatch repair deficient (dMMR) adenocarcinoma, which was determined by immunohistochemistry (ICH) test of endoscopic biopsy specimen. dMMR was defined as loss of nuclear expression of one or more MMR proteins.
• 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#
• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yu jiren: lead

Study Sites (8)

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

RECRUITING

The Second Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

NOT YET RECRUITING

Huzhou Central Hospital

Huzhou, Zhejiang, 313099, China

NOT YET RECRUITING

Lishui Central Hospital

Lishui, Zhejiang, 323000, China

NOT YET RECRUITING

Ningbo First Hospital

Ningbo, Zhejiang, 315010, China

NOT YET RECRUITING

Ningbo Medical Center LiHuiLi Hospital

Ningbo, Zhejiang, 315048, China

NOT YET RECRUITING

Ningbo Second Hospital

Ningbo, Zhejiang, 315099, China

NOT YET RECRUITING

Taizhou Hospital

Taizhou, Zhejiang, 317099, China

NOT YET RECRUITING

MeSH Terms

Conditions

Turcot syndrome

Interventions

toripalimab; Oxaliplatin; S 1 (combination)

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Jiren Yu

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiren Yu

CONTACT

0086-0571-87237931; yujr0909@zju.edu.cn

Kankai Zhu

CONTACT

zhukankai0401@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of gastrointestinal surgery department

Study Record Dates

• First Submitted: February 7, 2023
• First Posted: February 15, 2023
• Study Start: May 31, 2023
• Primary Completion: February 28, 2026
• Study Completion (Estimated): February 28, 2029
• Last Updated: July 25, 2023

Record last verified: 2023-02

Locations

CN (8)