Safety and Efficacy of Intraperitoneal Injection of METR-NK Cells as Neoadjuvant Therapy for Advanced Epithelial Ovarian Cancer

Официальное название

Safety and Efficacy of Intraperitoneal Injection of METR-NK Cells as Neoadjuvant Therapy for Advanced Epithelial Ovarian Cancer: A Single-arm, Single-center, Exploratory Clinical Study

Обзор

The goal of this type of clinical trial study is to evaluate the safety and efficacy of metabolic remodeling nature killer cells as neoadjuvant therapy in newly diagnosed patients with advanced ovarian cancer

Подробное описание

Peripheral blood will be collected from a vein of arm. Peripheral blood mononuclear cells (PBMc) will be isolated and purified for NK manufacturing. The addition of key metabolic molecules in the medium remodeled the metabolic network of NK cells, significantly reduced the aging phenomenon of NK cells in the culture process, improved the cell activity of NK cells and enhanced the cytotoxicity of NK cells. After 14 days cultivation, activated METR-NK will be harvested and formulated for clinical administration.

Вмешательства

• Препарат METR-NK cell(Metabolic Remodeling Nature Killer Cells)
  The minimum amount of METR-NK cells infused each time should be no less than 7.5×10\^7 cells, Continuous infusion for 2 days constitutes one course, with 4 courses. The infusion is given every 2 weeks.

Первичные конечные точки

• R0 resection rate [Срок оценки: 3-month]

Вторичные конечные точки (6)

• Overall Response Rate (ORR) After Neoadjuvant treatment [Срок оценки: 3-month]
• Pathological complete remission rate [Срок оценки: 3-month]
• Disease control rate [Срок оценки: 3-month]
• Progression free survival [Срок оценки: 2-years]
• Survival rate [Срок оценки: 3-years]
• Adverse event [Срок оценки: 3-month]

Критерии участия

Критерии включения

• Age: 18-70 years old (≥18, ≤70);
• Open surgery, laparoscopic surgery, or coarse needle biopsy for histopathological confirmation of advanced (FIGO IIIC/IV stage) high-grade serous ovarian cancer, high-grade endometrioid carcinoma, primary peritoneal carcinoma, and/or fallopian tube carcinoma, etc.;
• ECOG score: 0-1;
• Blood and tissue specimens before, during, and after treatment can be obtained, and subjects agree to submit blood and tissue specimens to the central laboratory for the purpose of expanding research in this trial;
• At least one lesion measurable by CT/MRI according to RECIST 1.1 criteria;
• Expected survival of at least 3 months;
• Patients judged by professional gynecologic oncologists as unable to achieve R0 resection or intolerant to surgery.

• Criteria for determining inability to achieve R0 resection include but are not limited to: Fagotti laparoscopic score ≥8 points; When laparoscopic evaluation is difficult to implement, an upper abdominal CT score ≥3 points may be used;
• Criteria for intolerance to surgery may include: Advanced age: age ≥70; Body mass index: BMI ≥40.0; Multiple chronic diseases; Malnutrition or hypoalbuminemia; Moderate to large amount of ascites; Newly diagnosed venous thromboembolism (survival period greater than 12 weeks);
• Major organ function meets the following criteria within 7 days before treatment: Hematological examination: Hemoglobin ≥90g/L, white blood cell count ≥3×10\^9/L, absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelets ≥90×10\^9/L; Kidney: Serum creatinine <1.5 mg/dL, glomerular filtration rate (GFR) ≥50 ml/min (based on the Fairview Laboratories formula at screening); Liver: AST, ALT, and alkaline phosphatase <3 times the upper limit of normal for the institution, total bilirubin <1.5 times the upper limit of normal for the institution; Lung function: Resting oxygen saturation ≥90%; Cardiac function: Left ventricular ejection fraction (LVEF) ≥40% by echocardiography, MUGA, or cardiac MRI; no evidence of uncontrolled angina, severe uncontrolled ventricular arrhythmias, or acute ischemia or active conduction system abnormalities on electrocardiography;
• No history of intestinal obstruction within two months;
• Reproductive-age patients must take effective contraceptive measures;
• Subjects voluntarily join this study and sign an informed consent form (ICF);
• Good compliance is expected, and subjects are able to follow up on efficacy and adverse reactions as required by the protocol.

Критерии исключения

• Patients who have received drugs or other cell immunotherapy in other clinical trials within 28 days before the screening period;
• Patients who have had other malignant tumors in the past 5 years;
• Acute illnesses are ongoing, or severe illnesses have occurred in the past 2 years, such as patients with active infections or fever, cardiovascular diseases (Grade III or IV heart failure), mental health issues (such as alcoholism, drug abuse);
• History of immunodeficiency, including HIV-positive status or other acquired, congenital immunodeficiency diseases;
• Organ transplant or organ failure patients, patients receiving immunosuppressive therapy after organ transplantation, or patients taking immunosuppressive drugs long-term;
• Thromboembolic events such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, and pulmonary embolism within 6 months;
• Known allergy to any component of the final product of METR-NK preparation, including human serum albumin;
• Breastfeeding during the screening period or female subjects with positive serum or urine pregnancy tests;
• Patients with mental illnesses, including epilepsy, dementia, severe depression, bipolar disorder, etc.;
• Other conditions deemed unsuitable for inclusion by the investigator.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Anhui Cancer Hospital — Хэфэй

Идентификаторы

NCT: NCT06395844 · 2024 No. 050

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗