NCT05745454Not yet recruitingNot Applicable
A Phase I Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor T-cell (CART) in the Treatment of Human Epidermalgrowth Factor Receptor-2 (HER2) Positive and Refractory Advanced Solid Tumors
su haichuan0 sites12 target enrollmentStarted: February 1, 2023Last updated:
Conditions
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 12
- Primary Endpoint
- Occurence of Adverse event rate
Study Overview
Brief Summary
This is a single-arm, investigator-initiated exploratory study.The study is designed to evaluate the safety and the tolerability of HER2-E-CART cells for the treatment of patients with HER2-positive, refractory advanced solid tumors in three dose groups: low, medium and high.
Detailed Description
This study was a one-arm,investigator-initiated exploratory study. According to the "3+3" principle, three dose groups with increasing dose were set up, namely low, medium and high dose groups, with separate cell counts. A total of 9-12 subjects were enrolled in the group and given intravenous infusion. Dose-limited toxicity was observed from the beginning of preconditioning to 28 days after CAR T infusion.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily signed an informed consent form and were able to complete the study procedures and follow-up examinations and treatment
- •Age ≥ 18 years and ≤ 70 years, regardless of gender
- •Weight > 40 kg
- •Eastern Cooperative Oncology Group (ECOG) physical status score of 0 to 1
- •Patients with refractory advanced solid tumors who have failed or are intolerant of existing standard regimens or whose patients have refused standard regimens
- •The presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors 1.1 criteria
- •With good organ function
- •Positive HER2 cell membrane expression
- •Women of childbearing potential must have a pregnancy test with negative results within 7 days prior to initiation of treatment
Exclusion Criteria
- •Any systemic antitumor therapy within 2 weeks prior to the single blood collection
- •History of organ transplantation
- •Pregnant or lactating women
- •Uncontrolled infectious disease, such as baseline Hepatitis B Virus DNA ≥ 1000 IU/ml, anti-HIV positive, Hepatitis C Virus-RNA positive
- •Other clinically significant active infections
- •Other active malignancies within the previous 5 years, such as basal or squamous skin cancer, superficial bladder cancer, or in situ breast cancer that has been completely cured and does not require follow-up treatment subjects are not included
- •Patients with severe autoimmune or immunodeficiency diseases, such as subjects with a confirmed diagnosis of a severe autoimmune disease requiring systemic immunosuppressive (steroid) therapy for a prolonged period of time (more than 2 months) or with immune-mediated symptomatic diseases, including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (e.g., Wegener's granulomatosis), etc
- •Subjects with known severe allergic reactions to pretreatment drugs such as injectable cyclophosphamide, injectable paclitaxel (albumin-bound), or CAR-T cell preparations including adjuvants, dimethylsulfoxide
- •Any unstable systemic disease: including but not limited to unstable angina pectoris, cerebrovascular accident or transient ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association (NYHA) classification ≥ Class III congestive heart failure, severe arrhythmias poorly controlled by medications, liver, kidney or metabolic disease, and hypertension uncontrolled by standard therapy 10
- •Those with active bleeding, thrombotic disorders requiring treatment
- •Patients with pericardial, thoracic, or abdominal effusions requiring clinical management or intervention
- •The presence of known or suspected brain metastases, including central nervous system and spinal cord compressions or meningeal metastases
- •Subjects undergoing treatment with systemic steroids or steroid inhalers
- •Subjects with any psychiatric disorder, including dementia, altered mental status, that may interfere with informed consent and understanding of relevant questionnaires
- •Having participated in another clinical trial within the previous 30 days
- •Have received a live or attenuated vaccine within 4 weeks prior to pretreatment
- •Those who have been judged by the investigator to have a serious uncontrollable disease or have other conditions that may interfere with receiving treatment in this study and are considered unsuitable
Outcomes
Primary Outcomes
Occurence of Adverse event rate
Time Frame: Adverse events will be collected from the beginning to the end of the study, up to 2 years after the last cell transfusion
The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs).
Secondary Outcomes
- Overall survival (OS)(Baseline up to death event.)
- Time to peak of serum cytokine Interleukin-2(Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.)
- Time to peak of serum cytokine Interleukin-6(Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.)
- Time to Maximum Plasma Concentration（Tmax）(Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.)
- Time to peak of serum cytokine Tumor Necrosis Factor-α(Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.)
- Objective Response Rate (ORR)(Baseline up to 144 weeks)
- Disease Control Rate (DCR)(Baseline up to 144 weeks)
- Progression Free Survival (PFS)(Baseline up to 144 weeks)
- Peak concentration (Cmax)(Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.)
- Time to peak of serum cytokine Interleukin-10(Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.)
- Time to peak of serum cytokine Tumor Necrosis Factor-γ(Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.)
- Effects on subjects' health-related quality of life(Baseline up to 144 weeks)
- Duration of Response (DOR)(Baseline up to 144 weeks)
- Area Under The Curve（AUC）(Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.)
- Elimination half-life (t1/2)-Single dose(Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360.)
Investigators
su haichuan
Head of Department
Tang-Du Hospital
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