Status:
UNKNOWN
NKG2D CAR-T Cells to Treat Patients With Previously Treated Liver Metastatic Colorectal Cancer
Lead Sponsor:
The Third Affiliated Hospital of Guangzhou Medical University
Collaborating Sponsors:
Hangzhou Cheetah Cell Therapeutics Co., Ltd
Conditions:
Refractory Metastatic Colorectal Cancer
Eligibility:
All Genders
18-75 years
Phase:
EARLY_PHASE1
Brief Summary
Evaluate the clinical safety and feasibility of NKG2D CAR-T administrated by hepatic artery transfusion for patients with previously treated liver metastatic colorectal cancer.
Detailed Description
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 to...
Eligibility Criteria
Inclusion
- 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.
- 8\. 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.
- 9\. 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.
- 10\. Negative urine or serum pregnancy tests in women of reproductive age within 7 days prior to treatment.
Exclusion
- 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).
- 12\. 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.
- 13\. 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.
- 14\. Presence of interstitial lung disease, non-infectious pneumonia or uncontrolled systemic disease (e.g., diabetes, hypertension, pulmonary fibrosis and acute pneumonia).
- 15\. 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.
- 16\. 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.
- 17\. Positive pregnancy test before first use in women who are pregnant or breast-feeding or who are at risk of pregnancy.
- 18\. 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.
- 19\. There are serious psychological or mental abnormalities. 20. Participated in clinical trials of other drugs within 4 weeks.
Key Trial Info
Start Date :
September 13 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 1 2022
Estimated Enrollment :
9 Patients enrolled
Trial Details
Trial ID
NCT05248048
Start Date
September 13 2021
End Date
October 1 2022
Last Update
February 21 2022
Active Locations (1)
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1
The Third Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China