A Multi-center, Phase II Study to Evaluate Efficacy and Safety of Perioperative Chemotherapy With Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel (FLOT) and Trastuzumab in Combination With Toripalimab in Patients With HER2 Positive Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma

Yu jiren8 sites in 1 country30 target enrollmentFebruary 28, 2023

ConditionsAdenocarcinoma of the Stomach Adenocarcinoma of Esophagogastric Junction HER2-positive Gastric Cancer

InterventionsToripalimab Trastuzumab 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT)

DrugsToripalimab Trastuzumab 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT)

Overview

Phase: Phase 2
Intervention: Toripalimab
Conditions: Adenocarcinoma of the Stomach
Sponsor: Yu jiren
Enrollment: 30
Locations: 8
Primary Endpoint: Rate of pathological complete responses (pCR)
Status: Recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

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 chemotherapy with FLOT regimen and trastuzumab in combination with toripalimab in participants with resectable HER2 positive locally advanced gastric or esophagogastric junction adenocarcinoma.

Registry

clinicaltrials.gov

Start Date

February 28, 2023

End Date

March 1, 2028

Last Updated

3 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).
•The gender is not limited. Age: ≥ 18 years and ≤ 80 years old.
•Gastric or esophagogastric junction adenocarcinoma confirmed by pathology.
•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.
•Clinical stage at presentation: cT2-T4b, N+/-, M0 as determined by AJCC staging system, 8th edition.
•The definition of metastatic lymph nodes: a lymph node must be ≥ 10mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm) according to the guideline of Response Evaluation Criteria in Solid Tumours (RECIST version 1.1)
•Participants with a performance status of 0 \~ 1 on the Eastern Cooperative Oncology Group (ECOG) within 7 days before the first dose of study treatment.
•Life expectancy ≥ 6 months.
•Agreement of providing pretreatment endoscopic biopsies specimens and surgical specimens for biomarker analysis, as well as the peripheral blood, feces and urine sample.
•The functions of the vital organs meet requirements as follow (within 14 days before the first dose of study treatment, participant has not received treatment of recombinant human thrombopoietin or granulocyte stimulating factor):

Exclusion Criteria

•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 for 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.

Arms & Interventions

Toripalimab plus Trastuzumab with FLOT(5-FU+leucovorin+docetaxel+oxaliplatin)

Intervention: Toripalimab

Toripalimab plus Trastuzumab with FLOT(5-FU+leucovorin+docetaxel+oxaliplatin)

Intervention: Trastuzumab

Toripalimab plus Trastuzumab with FLOT(5-FU+leucovorin+docetaxel+oxaliplatin)

Intervention: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT)

Outcomes

Primary Outcomes

Rate of pathological complete responses (pCR)

Time Frame: From enrollment to surgery after pre-operative treatment (up to approximately 24 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 enrollment to the end of follow up or death from any cause (up to approximately 60 months))
Progression-free survival(From enrollment to the end of follow up or the time of disease progression or relapse or death from any cause (up to approximately 60 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 27 months))