NCT05248048Unknown早期 1 期
Hepatic Artery Transfusion of NKG2D CAR-T Cells to Treat Patients With Previously Treated Liver Metastatic Colorectal Cancer: a Prospective, Multicenter Clinical Trial
The Third Affiliated Hospital of Guangzhou Medical University1 个研究点 分布在 1 个国家目标入组 9 人开始时间: 2021年9月13日最近更新:
适应症
干预措施
试验速览
- 阶段
- 早期 1 期
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Maximal Tolerable Dose#MTD#
研究概览
简要总结
Evaluate the clinical safety and feasibility of NKG2D CAR-T administrated by hepatic artery transfusion for patients with previously treated liver metastatic colorectal cancer.
详细描述
Evaluate the clinical safety and feasibility of NKG2D CAR-T administrated by hepatic artery transfusion for patients with previously treated liver metastatic colorectal cancer. Evaluate the maximum tolerated dose (MTD), dose limiting toxicities (DLT), and toxicity spectrum of NKG2D CAR-T treatment administrated by hepatic artery transfusion. Secondary Objectives: Evaluate the efficacy of NKG2D CAR-T administrated by hepatic artery transfusion for patients with previously treated liver metastatic colorectal cancer, including PSF, DCR, SD >= 8 weeks, ORR, OS, and DOR.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Prior to performing any study protocol-related procedures other than routine care, a voluntarily signed and dated subject informed Consent Form (ICF) must be obtained in accordance with regulatory and institutional guidelines.
- •Aged 18-75 years.
- •There is definite histological evidence of adenocarcinoma of the colon or rectum.
- •The Eastern Cooperative Oncology Group (ECOG) performance Status (PS) score was 0-1 (see Appendix 1).
- •Liver metastasis was confirmed by PET-CT, CT, MR, and/or intraoperative exploration (histological diagnosis is not required).
- •According to the response evaluation criteria in solid Tumors (RECIST) (Version 1.1), patients have at least one target lesion with a measurable diameter line (CT scan of tumor lesion length >= 10 mm, The short diameter of CT scan of lymph node lesions >= 15 mm, and the scanning layer thickness is no more than 5 mm).
- •Failure of treatment after previous standard chemotherapy for metastatic colorectal cancer (including disease progression and unacceptable adverse reactions):
- •(1)Chemotherapy regimens must include fluorouracil (5-fluorouracil/capecitabine /S-1), oxaliplatin and irinotecan (2)Patients receiving oxaliplatin in adjuvant therapy should develop disease progression during adjuvant therapy or within 6 months after completion of adjuvant therapy; (3)patients may have previously received bevacizumab and/or cetuximab and/or rigfinil and/or furoquitinib.
- •The primary tumor of the colon or rectum has been surgically removed, or the liver metastases are considered to be irretrievable after the evaluation of a multidisciplinary colorectal cancer team consisting of at least two gastrointestinal surgeons, one hepatobiliary surgeon, one oncologist, one interventional surgeon, and one radiologist.
- •The following laboratory test values obtained during the root screening period (reaching the standard and stable before participating in the study) have appropriate organ functions: Neutrophil count >= 1.5 x 109/L, platelet count >= 75 x 10^9/L, serum total bilirubin <= upper normal limits UNL), aspartate aminotransferase <= 2 x UNL, alanine aminotransferase <= 2 x UNL, serum creatinine <= 1.5 x UNL.
- •Negative urine or serum pregnancy tests in women of reproductive age within 7 days prior to treatment.
排除标准
- •The presence or co-existence of other active malignancies (other than those that have been curable for more than 5 years and have received curative treatment or carcinoma in situ that can be cured with adequate treatment).
- •Subjects have central nervous system metastasis or previous brain metastases.
- •Had received hepatic arterial infusion chemotherapy, hepatic arterial embolization chemotherapy or hepatic radiotherapy within 3 months.
- •Received liver surgery (except biopsy for liver metastasis) and liver interventional ablation within the previous 3 months.
- •CT angiography showed severe arterial embolism or hepatic arterial variation.
- •Partial prothrombin time (APTT) or prothrombin time (PT) exceeded 1.5 x ULN (based on the normal value in the clinical trial research center), or patients with evidence or history of bleeding tendency within 2 months prior to enrollment, regardless of severity.
- •Active infection less than 7 days after completion of systemic antibiotic therapy.
- •Major surgery or severe trauma, such as laparotomy, thoracotomy, laparoscopic viscerectomy, etc. within 4 weeks prior to enrollment (surgical incisions should be completely healed before randomization).
- •Active coronary artery disease, severe/unstable angina or newly diagnosed angina or myocardial infarction within 12 months prior to enrollment.
- •Thrombosis or embolism events, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, and deep vein thrombosis, occurred within 12 months prior to enrollment.
- •The New York Heart Association (NYHA) has grade II congestive Heart failure or higher (see Appendix 2).
- •Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis (hepatitis B, defined as HBV-DNA >= 500 IU/ mL; Hepatitis C, defined as hcV-RNA higher than the lower limit of the assay) or co-infection with hepatitis B and c.
- •Presence of any active, known or suspected autoimmune disease. Subjects who are in a stable state and do not require systemic immunosuppressive therapy, such as type I diabetes, hypothyroidism requiring only hormone replacement therapy, and skin conditions that do not require systemic therapy (e.g., vitiligo, psoriasis, and hair loss) are allowed to be enrolled.
- •Presence of interstitial lung disease, non-infectious pneumonia or uncontrolled systemic disease (e.g., diabetes, hypertension, pulmonary fibrosis and acute pneumonia).
- •Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) grade 2 or above toxicity (except anaemia, hair loss, skin pigmentation) arising from any prior treatment that has not subsided.
- •Programmed death-1 within 3 months Pd-1) or its ligand (PD-L1) antibody, anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibody, or other drugs/antibodies that act on T cell co-stimulation or checkpoint pathways.
- •Positive pregnancy test before first use in women who are pregnant or breast-feeding or who are at risk of pregnancy.
- •The investigator considers that the subject has any clinical or laboratory abnormalities or compliance issues that make it inappropriate to participate in this clinical study.
- •There are serious psychological or mental abnormalities.
- •Participated in clinical trials of other drugs within 4 weeks.
研究组 & 干预措施
NKG2D CAR-NK
Experimental
CAR-T infusion
干预措施: CAR-T infusion (Biological)
结局指标
主要结局
Maximal Tolerable Dose#MTD#
时间窗: 28 days
tolerability evaluation
Dose-Limiting Toxicity#DLT#
时间窗: 28 days
Safety
次要结局
- Antitumor efficacy-Objective response rate (ORR)(52 weeks)
- Antitumor efficacy-Overall survival (OS)(52 weeks)
研究者
研究点 (1)
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