Breast Cancer, Colorectal Cancer, Gastric Cancer, Glioma, Lung Cancer, Ovarian Cancer, Pancreatic Cancer
Conditions
Keywords
HER2 CAR-T, safety, efficiency, refractory and relapsed cancer
Brief summary
Chimeric antigen receptor T cells (CAR-T) therapy has not yet been fully explored in solid tumors. Human epidermal growth factor receptor-2(HER2) is widely expressed in cancers. Investigators have developed anti-HER2 CAR-modified T cells and validated the efficiency targeting HER2-positive cancer in preclinical studies. This study is aimed to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, CAR-T cells persistence, tumor elimination and disease status after treatment will be evaluated.
Interventions
BIOLOGICALAnti-HER2 CAR-T
HER-2-targeting CAR-T cells infusion in HER2 positive cancers
Sponsors
Zhi Yang
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Relapsed or refractory HER2 positive cancer. 2. KPS\>60. 3. Life expectancy\>3 months. 4. Gender unlimited, age from 18 years to 80 years. 5. Assessable lesions with a minimum size of 10mm by CT scan or MRI. 6. Acceptable organ function Hematology: * Absolute neutrophil count greater than 800/mm\^3 without the support of filgrastim. * White blood cell (WBC) (\> 2000/mm\^3). * Platelet count greater than 50,000/mm\^3. * Hemoglobin greater than 9.0 g/dl. Chemistry: * Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 3 times the upper limit of normal (patients without liver metastasis) or 6 times the upper limit of normal (patients with liver metastasis). * Serum creatinine less or equal to 3 times the upper limit of normal * Total bilirubin less than or equal to 3 times the upper limit of normal. 7. No other serious diseases(autoimmune disease, immunodeficiency etc.). 8. Adequate cardiac function(LVEF≥40%). 9. No other tumors. 10. Patients volunteer to participate in the research.
Exclusion criteria
1. Allergic to cytokines. 2. Uncontrolled active infection. 3. Acute or chronic GVHD. 4. MODS. 5. Treated with T cell inhibitor. 6. HIV affected. 7. Other situations improper for the research.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the toxicity profile of the HER2 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0. | 3 years | Observe and handle the toxicity profile of the HER2 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival time of Anti-HER2 CAR T cells in vivo. | 1 year | Detect the existence of CAR-T cells in the blood of participants through qPCR or flow cytometry. |
| Efficacy of anti-HER2 CAR T cells to confirm the ability of CAR T cells to eliminate HER2 positive cancer cells | 12 weeks | Evaluate the anti-tumor efficacy of CAR-T therapy by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and Immune-Related Response Criteria（iRECIST）. |
| Maximum tolerated dose (MTD) of HER2 targeted CAR T cells | 4 weeks | Determine the maximum tolerated dose of each participant through the grades of side effects. |
Countries
China
Outcome results
None listed