Phase I Clinical Trial of CT0181 Cells in the Treatment of Hepatocellular Carcinoma
Study Details
Study Description
Brief Summary
A Phase I Clinical Study of CT0181 cells in Patients with Advanced Hepatocellular Carcinoma
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Primary objectives:
Evaluate the safety and tolerance of CT0181 cells in patients with advanced hepatocellular carcinoma within 28 days after the first infusion
Secondary objectives:
Evaluate the metabolic kinetics of CT0181 cells ; Evaluate overall safety and tolerability ; Evaluate the initial efficacy of CT0181 cell infusion in the treatment of advanced hepatocellular carcinoma with positive Glypican-3（GPC3 ）expression.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 5 dose levels each with or without lymphocyte clearance were tentatively determined. CT0181 Cells were transfused after lymphocyte clearance with fludarabine and cyclophosphamide or without lymphocyte clearance. |
Biological: CT0181 Cells
5 dose levels each with or without lymphocyte clearance were tentatively determined.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 1.Dose-Limiting Toxicity（DLT） [28days]
Safety
- Maximal Tolerable Dose（MTD） [28days]
tolerability evaluation
- Treatment Emergent Adverse Event（TEAE） [28days]
Incidence rate
- Adverse Event of Special Interest [28 days]
Incidence rate
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Aged 18 to 75 years, either sex；
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Patients with clinically or pathologically confirmed hepatocellular carcinoma were treated with surgery or local treatment It is not suitable for surgery or local radical treatment;
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Progression or intolerance after at least one previous systemic treatment, or due to specific reasons unable to receive systemic treatment.
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According to Barcelona Clinic Liver Cancer（BCLC）, the patients are classified into Grade C or Grade B unsuitable for local treatment/progressive disease after local treatment;
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In tumor tissue samples GPC3 is detected positive by immunohistochemistry (IHC);
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According to Response Evaluation Criteria in SolidTumors（RECIST1.1）,patients have at least one evaluable target lesion;
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Expected survival is > 12 weeks;
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Cirrhosis status Child-Pugh score: ≤7
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Eastern Cooperative Oncology Group Performance Status score: 0 to 1 point;
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If the patient is HBsAg positive or HBcAb positive, DNA of the hepatitis B virus should be <2000 IU/ml. HBsAg positive patients must receive antiviral treatment ;
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Acceptable routine blood test showing no contraindication to the lymphodepletion pretreatment and adequate liver, renal, cardiovascular, respiratory function;
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Have venous accesses for apheresis;
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Subjects of childbearing age must undergo a serum pregnancy test . In addition, they should be willing to use a reliable method of contraception during the trial (within 52 weeks after cell infusion); male subjects whose spouses are women of childbearing age should undergo sterilization surgery or agree to use a reliable method of contraception during the trial; Understand and sign informed consent.
Exclusion Criteria:
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Pregnant or breast-feeding women;
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Hepatitis virus C antibodies ,Human Immunodeficiency Virus（HIV） antibodies or Syphilis Serological tests are positive;
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Any uncontrol active infection, including but not limited to active tuberculosis;
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Have clinically significant thyroid dysfunction except the stable control after treatment;
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Previous or present hepatic encephalopathy;
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Current clinically significant ascites;
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Imaging results:≥50% of the liver is replaced by tumor or portal vein main tumor thrombus, or metastases to the central nervous system, or tumor thrombus invasion of mesenteric vein / inferior vena cava;
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Subjects have known active autoimmune diseases
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The side effects caused by the previous treatment of the subjects did not return to Common Terminology Criteria for Adverse Events（CTCAE） ≤1; except hair loss and other tolerable events determined by investigator;
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Patients who had received systemic steroids or other immunosuppressive agents within 7 days before apheresis, except inhaled steroids;
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History of severe allergy ;
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Has signs of central nervous system disease or an abnormal neurological examination with clinical significance;
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Subjects with unstable or active ulcers, gastrointestinal bleeding, or pump inhibitor intolerance;
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Patients with a history of organ transplantation or waiting for organ transplantation;
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Previously received Programmed cell Death-1/Programmed cell Death-Ligand 1 monoclonal antibody therapy within 4 weeks or local treatment and systemic chemiotherapy within 2 weeks or immunotheray and molecular targeted drugs within 1 week before apheresis;
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Previously received GPC3 targeted therapy;
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Major surgery or significant trauma occurred within 4 weeks before apheresis, or it is expected that major surgery needs to be performed during the trial;
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Patients who had incurable malignant tumors in the past 5 years or at the same time, except cervical cancer in situ and basal cell carcinoma of skin;
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Other serious diseases that may restrict the subjects from participating in the trial ；
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The researcher assessed that the subjects were unable or unwilling to comply with the requirements of the trial protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University | Beijing | Beijing | China | 100142 |
Sponsors and Collaborators
- Peking University
- CARsgen Therapeutics Co., Ltd.
Investigators
- Principal Investigator: Lin Shen, Peking University Cancer Hospital & Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CT0181-CG1202