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| Name | Class |
|---|---|
| Hangzhou Cheetah Cell Therapeutics Co., Ltd | OTHER |
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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 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NKG2D CAR-NK | Experimental | CAR-T infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CAR-T infusion | Biological | NKG2D CAR-NK Cell Therapy in Patients With Refractory Metastatic Colorectal Cancer |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-Limiting Toxicity#DLT# | Safety | 28 days |
| Maximal Tolerable Dose#MTD# | tolerability evaluation | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Antitumor efficacy-Objective response rate (ORR) | The number of cases in which tumor size is reduced to partial response (PR) or complete response (CR) / the total number of evaluable cases (%). | 52 weeks |
| Antitumor efficacy-Overall survival (OS) |
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Inclusion Criteria:
(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 Criteria:
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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xuehu Xu, MD | Contact | 13609020099 | 0086 | maxtiger@126.com |
| Nanqi Huang | Contact | 13560316181 |
| Name | Affiliation | Role |
|---|---|---|
| Xuehu Xu, MD | The Third Affiliated Hospital of Guangzhou Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Third Affiliated Hospital of Guangzhou Medical University | Recruiting | Guangzhou | Guangdong | China |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D016219 | Immunotherapy, Adoptive |
| D055655 | NK Cell Lectin-Like Receptor Subfamily K |
| D001336 | Automobiles |
| D002452 | Cell Count |
| ID | Term |
|---|---|
| D019264 | Adoptive Transfer |
| D007116 | Immunization, Passive |
| D007114 | Immunization |
| D007167 | Immunotherapy |
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The period from the first study treatment to any cause of death
| 52 weeks |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D056747 |
| Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D007158 | Immunologic Techniques |
| D008919 | Investigative Techniques |
| D055630 | Receptors, NK Cell Lectin-Like |
| D055607 | Receptors, Natural Killer Cell |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D018986 | Motor Vehicles |
| D014186 | Transportation |
| D013676 | Technology, Industry, and Agriculture |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D002468 | Cell Physiological Phenomena |