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 enrollmentFebruary 2023

ConditionsSolid Tumor

Overview

Phase: N/A
Intervention: Not specified
Conditions: Solid Tumor
Sponsor: su haichuan
Enrollment: 12
Primary Endpoint: Occurence of Adverse event rate
Status: Not Yet Recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

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.

Registry

clinicaltrials.gov

Start Date

February 2023

End Date

December 2025

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

su haichuan

Responsible Party

Sponsor Investigator

Principal Investigator

su haichuan

Head of Department

Tang-Du Hospital

Eligibility Criteria

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

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.)