NKG2D CAR-T Cells to Treat Patients With Previously Treated Liver Metastatic Colorectal Cancer

NCT05248048 | Unknown Early Phase 1

• 1 other identifier: CART-002
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory Metastatic Colorectal Cancer

Keywords

Refractory Metastatic Colorectal Cancer; NKG2D; CAR-NK

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity#DLT#

  Safety

  28 days

• Maximal Tolerable Dose#MTD#

  tolerability evaluation

  28 days

Secondary Outcomes (2)

• Antitumor efficacy-Objective response rate (ORR)

  52 weeks

• Antitumor efficacy-Overall survival (OS)

  52 weeks

Study Arms (1)

NKG2D CAR-NK

EXPERIMENTAL

CAR-T infusion

Biological: CAR-T infusion

Interventions

CAR-T infusion BIOLOGICAL

NKG2D CAR-NK Cell Therapy in Patients With Refractory Metastatic Colorectal Cancer

Also known as: Natural killer group 2 member D (NKG2D) ligand-targeting chimeric antigen receptor (CAR) natural killer (NK) cells

NKG2D CAR-NK

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Third Affiliated Hospital of Guangzhou Medical University: lead
• Hangzhou Cheetah Cell Therapeutics Co., Ltd: collaborator

Study Sites (1)

The Third Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Immunotherapy, Adoptive; NK Cell Lectin-Like Receptor Subfamily K; Automobiles; Cell Count

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Receptors, NK Cell Lectin-Like; Receptors, Natural Killer Cell; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Motor Vehicles; Transportation; Technology, Industry, and Agriculture; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cell Physiological Phenomena

Study Officials

• Xuehu Xu, MD

  The Third Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuehu Xu, MD

CONTACT

13609020099; maxtiger@126.com

Nanqi Huang

CONTACT

13560316181

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: February 21, 2022
• Study Start: September 13, 2021
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: February 21, 2022

Record last verified: 2022-02

Locations

CN (1)