NCT06155383招募中2 期
A Phase II Study of Perioperative Disitamab Vedotin Plus Toripalimab and XELOX Versus Disitamab Vedotin Plus Toripalimab Versus XELOX in Subjects With HER2-expressing Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 90
- 试验地点
- 11
- 主要终点
- Pathological complete response (pCR) rate
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of perioperative Disitamab Vedotin plus Toripalimab and XELOX versus Disitamab Vedotin plus Toripalimab versus XELOX in subjects with HER2-expressing resectable locally advanced gastric or gastroesophageal junction adenocarcinoma.
详细描述
This is an open-label, randomized, multicenter, open-label clinical trial designed to evaluate safety and efficacy of perioperative Disitamab Vedotin plus Toripalimab and XELOX versus Disitamab Vedotin plus Toripalimab versus XELOX in subjects with HER2-expressing (immunohistochemical 1+, 2+, 3+) resectable locally advanced gastric or gastroesophageal junction adenocarcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily participate and sign the informed consent form;
- •Male or female, ≥18 years;
- •Patients with gastric or gastroesophageal junction adenocarcinoma confirmed by histopathology;
- •Clinical stage cT3-4aN+, no distant metastasis (M0);
- •According to the baseline imaging and medical history data evaluated by the Investigators, radical surgery for gastric cancer and R0 resection is expected; Subjects had not previously received any antitumor therapy for gastric or gastroesophageal junction adenocarcinoma;
- •HER2- expression: IHC 1+, 2+, 3+;
- •ECOG performance status score of 0 or 1;
- •Cardiac function: left ventricular ejection fraction ≥50%;
- •The following criteria should be met within 7 days prior to study dosing (normal values are based on the clinical trial center):
- •9.1Bone marrow function:
- •absolute neutrophil count (ANC) ≥1.5×109/L (no treatment with granulocyte colony-stimulating factor within 1 week prior to examination);
- •Platelets ≥100×109/L (platelets should not be transfused within 1 week before the examination, and recombinant human thrombopoietin therapy should not be used within 2 weeks)
- •hemoglobin ≥9g/dL (blood transfusion and erythropoietin treatment are not allowed within 2 weeks prior to the examination);
- •9.2Liver function:
- •Serum total bilirubin ≤1.5 times the upper limit of normal (ULN);
- •alanine amino transferase (ALT) and aspartate amino transferase (AST) ≤2.5 × ULN;
- •9.3 Kidney function:
- •a.Blood creatinine ≤1.5×ULN or creatinine clearance (CrCl) ≥50 mL/min according to Cockcroft-Gault formula method; Female: CrCl= (140-age) × weight (kg) × 0.85 72 × serum creatinine (mg/dL) Male: CrCl= (140-age) × weight (kg) × 1.00 72 × serum creatinine (mg/dL)
- •9.4 Coagulation function:
- •prothrombin time (PT) ≤1.5×ULN;
- •thrombin time (TT) ≤ 1.5×ULN;
- •activated partial thromboplastin time (APTT) ≤ 1.5×ULN.
- •Female subjects should be surgically sterilized, postmenopausal, or agree to use at least one medically acceptable method of contraception (e.g., intrauterine device, contraceptives, or condoms) for 7 days before the first dose and for 6 months after the end of the study treatment period, and not breastfeed. Blood pregnancy tests must be negative within 7 days prior to study enrollment. Male subjects should agree to use at least one medically approved contraceptive method (e.g., condoms, abstinence, etc.) for 7 days prior to initial dosing and up to 6 months after the end of the study treatment period;
- •Able to understand trial requirements, willing and able to follow trial and follow-up procedures.
排除标准
- •Received any anti-tumor therapy for gastric or gastroesophageal junction adenocarcinoma before study dosing, including chemotherapy, radiotherapy, targeted therapy, immunotherapy and other anti-tumor drug therapy (including Chinese medicine treatment with anti-tumor ingredients specified in the instructions within 2 weeks before screening);
- •The investigators considered perioperative period treatment of patients requiring radiotherapy for target lesions；
- •Major surgery was performed within 4 weeks before the start of study dosing and did not fully recover;
- •Patients with active gastrointestinal bleeding or high risk of bleeding within 2 weeks prior to screening;
- •Gastrointestinal perforation/fistula 6 months before screening;
- •Upper digestive tract obstruction that cannot guarantee drug absorption, functional abnormalities or malabsorption syndrome, which can affect the absorption of capecitabine ;
- •Peripheral polyneuropathy ≥ NCI Ⅱ grade；
- •Serum virology examination (based on the normal value of the research center):
- •Positive HBsAg test with positive HBV DNA copy number;
- •Positive HCVAb test with positive HCV RNA PCR test.
- •Positive HIVAb test.
- •Have received live vaccine within 4 weeks prior to screening or plan to receive any vaccine during the study period (except for the novel coronavirus vaccine);
- •Heart failure rated 3 or higher by the New York College of Cardiology (NYHA);
- •Cardiac chest pain, defined as moderate pain that restricts daily activities, occurred within 28 days prior to screening. There were serious arteriovenous thrombosis events or cardiovascular and cerebrovascular accidents within six months before dosing, such as deep vein thrombosis (except asymptomatic and untreated intermuscular venous thrombosis), pulmonary embolism, cerebral infarction, cerebral hemorrhage, and myocardial infarction (except asymptomatic lacunar infarction that did not require clinical intervention);
- •There is an active or advanced infection that requires systematic treatment (experimental medication may be initiated 2 weeks after the end of anti-infective therapy), such as active tuberculosis;
- •There are systemic diseases that have not been stably controlled which are determined by investigators, including diabetes, hypertension, cirrhosis, etc.;
- •A history of lung disease that requires treatment and has the potential to interfere with surgery, including but not limited to interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, and acute lung disease;
- •Active autoimmune diseases requiring systemic therapy (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressive drugs) within 2 years prior to dose administration, and replacement therapies (e.g., thyroxine, insulin, or physiological replacement of glucocorticoids due to renal or pituitary deficiency) are allowed, and a history of refractory autoimmune disease. Systemic use of steroids within 14 days prior to screening (dose > 10 mg/day prednisone or equivalent dose of other glucocorticoids) or other systemic immunosuppressive therapy;
- •Other malignancies within 5 years prior to screening, other than those that have been cured after treatment (including but not limited to adequately treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or breast ductal carcinoma in situ treated with radical surgery);
- •Previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
- •Allergies to any of the drugs in this study;
- •Known deficiency of dipyrimidine dehydrogenase (DPD);
- •Receiving immunotherapy (including but not limited to interleukin, interferon, thymus hormone) or other investigational drugs within 28 days prior to screening;
- •Pregnant or lactating women;
- •Any other disease, metabolic disorder, or abnormal findings upon physical examination or laboratory examination that makes the subject unsuitable for receiving the investigational drug, affects the interpretation of study outcomes, or poses risks to patient safety, as determined by the investigator;
- •Subject is assessed to be unable or unwilling to comply with the requirements of the protocol.
研究组 & 干预措施
XELOX (capecitabine + oxaliplatin)
Active Comparator
capecitabine with oxaliplatin arm
干预措施: Capecitabine (Drug)
XELOX (capecitabine + oxaliplatin)
Active Comparator
capecitabine with oxaliplatin arm
干预措施: oxaliplatin (Drug)
Disitamab Vedotin + Toripalimab
Experimental
Disitamab Vedotin with Toripalimab arm
干预措施: Disitamab Vedotin (Drug)
Disitamab Vedotin + Toripalimab
Experimental
Disitamab Vedotin with Toripalimab arm
干预措施: Toripalimab (Drug)
Disitamab Vedotin + Toripalimab + XELOX
Experimental
Disitamab Vedotin + Toripalimab + XELOX arm
干预措施: Capecitabine (Drug)
Disitamab Vedotin + Toripalimab + XELOX
Experimental
Disitamab Vedotin + Toripalimab + XELOX arm
干预措施: oxaliplatin (Drug)
Disitamab Vedotin + Toripalimab + XELOX
Experimental
Disitamab Vedotin + Toripalimab + XELOX arm
干预措施: Disitamab Vedotin (Drug)
Disitamab Vedotin + Toripalimab + XELOX
Experimental
Disitamab Vedotin + Toripalimab + XELOX arm
干预措施: Toripalimab (Drug)
结局指标
主要结局
Pathological complete response (pCR) rate
时间窗: Up to approximately 2 years
Proportion of patients with pCR. pCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes (ypT0N0)
次要结局
- Objective remission rate (ORR)(Up to approximately 2 years)
- Tumor regression grade (TRG) score(Up to approximately 2 years)
- Major pathological response (MPR)(Up to approximately 2 years)
- Event free survival (EFS)(Up to approximately 2 years)
- R0 resection rate(Up to approximately 2 years)
- Overall survival (OS)(Up to approximately 2 years)
- Adverse events(Time Frame: Up to approximately 2 years)
研究者
研究点 (11)
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