Perioperative Chemotherapy Combined With Serplulimab or Placebo for pMMR Locally Advanced Gastric Adenocarcinoma (FOCUS-05)

Официальное название

Perioperative S-1 Plus Oxaliplatin Combined With Serplulimab or Placebo for Locally Advanced Gastric Adenocarcinoma With Proficient Mismatch Repair: a Prospective, Multi-center, Double-blinded, Randomized Placebo-controlled Study

Обзор

This phase II study is a prospective, multi-center, double-blinded, and randomized trial to compare the efficacy and safety of perioperative SOX plus serplulimab with SOX plus placebo for locally advanced gastric adenocarcinoma with proficient mismatch repair

Вмешательства

• Препарат S1
  S-1 orally intake as perioperative chemotherapy
• Препарат Oxaliplatin
  Oxaliplatin (130 mg/m2) infusion as perioperative chemotherapy
• Препарат Serplulimab
  Perioperative serplulimab, 300 mg IV infusion
• Препарат Placebo
  Perioperative placebo, 300 mg IV infusion

Первичные конечные точки

• Rate of pathological complete responses (pCR) [Срок оценки: From enrollment to surgery after pre-operative treatment (up to approximately 36 months)]

Вторичные конечные точки (3)

• Overall survival [Срок оценки: From enrollment to the end of follow up or death from any cause (up to approximately 60 months)]
• Progression-free survival [Срок оценки: 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) [Срок оценки: From enrollment to 90-day after the last dose administration (up to approximately 27 months)]

Критерии участия

Критерии включения

• 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, and proficient mismatch repair confirmed by immunohistochemistry.
• 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):

8.1 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) ≥ 90 g / L.

8.2 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) ≥ 30 g / L.

8.3 Renal function： Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 60 ml / min for those with creatinine level > 1.5 × ULN.

8.4 Coagulation function： International normalized ratio (INR) ≤ 1.5; Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.

• Female 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 serplulimab, or 180 days after the last dose of chemotherapy, whichever is longer, and should not be breastfeeding.
• For the 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 serplulimab, or 180 days after the last dose of chemotherapy, whichever is longer).

Критерии исключения

• HER2-positive, EBER-positive or dMMR.
• 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

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

Идентификаторы

NCT: NCT05872685 · IIT20230020C-R1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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