Perioperative Chemotherapy Plus Trastuzumab Plus Toripalimab in HER2 Positive Locally Advanced Gastric or Esophagogastric Junction Adenocarcinoma

NCT05715931 | Recruiting Phase 2

• 1 other identifier: IIT20220076C-R1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 8

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.

Conditions

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

Keywords

Gastric Adenocarcinoma; Esophagogastric Junction Adenocarcinoma; Perioperative Chemotherapy; Trastuzumab; Toripalimab

Outcome Measures

Primary Outcomes (1)

• 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.

  From enrollment to surgery after pre-operative treatment (up to approximately 24 months)

Secondary Outcomes (3)

• 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)

Study Arms (1)

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

EXPERIMENTAL

Drug: Toripalimab; Drug: Trastuzumab; Drug: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT)

Interventions

Toripalimab DRUG

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

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

Trastuzumab DRUG

Trastuzumab, 8 mg/kg IV loading dose at 1st administration and then 6 mg/kg IV on Day 1 of each 21 day cycle for 3 cycles before surgery and 3 cycles after surgery. The first administration of trastuzumab after surgery should also be given at the loading dose of 8 mg/kg.

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

5-FU, leucovorin, docetaxel, oxaliplatin (FLOT) DRUG

Pre-operative treatment 4 cycles and post-operative treatment 4 cycles: Docetaxel 50 mg/m², IV on day 1 of each 14 day cycle; Oxaliplatin 85 mg/m² , IV on day 1 of each 14 day cycle; Leucovorin 200 mg/m² or Levoleucovorin 100 mg/m², IV on day 1 of each 14 day cycle; 5-FU 2600 mg/m², IV over 24 h on day 1 of each 14 day cycle.

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

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).
• 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):
• 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) ≥ 90 g / L.

You may not qualify if:

• 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.
• 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.

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

Interventions

toripalimab; Trastuzumab; Fluorouracil; Leucovorin; Docetaxel; Oxaliplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

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

Study Design

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

Model Details: Drug: 5-FU, leucovorin, docetaxel, oxaliplatin (FLOT) Drug: Trastuzumab Drug: Toripalimab

Study Record Dates

• First Submitted: January 28, 2023
• First Posted: February 8, 2023
• Study Start: February 28, 2023
• Primary Completion: March 1, 2025
• Study Completion (Estimated): March 1, 2028
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

CN (8)