Advanced HER-2 Positive Solid Tumors, Chemotherapy Refactory, HER-2 Antibody Inhibitor Therapy Refactory
Conditions
Keywords
CART-HER-2, HER-2 positive, Advanced, Refactory, Solid tumors
Brief summary
RATINALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous T cells may make the body build immune response to kill cancer cells. PURPOSE: This clinical trial is to study genetically engineered lymphocyte therapy in treating patients with HER-2 positive advanced solid tumors,such as breast cancer, gastric cancer, hepatic carcinoma, endometrial cancer and ovary cancer.
Detailed description
PRIMARY OBJECTIVES: I.Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with anti-HER-2 vector(referred to as CART-HER-2 cells). II.Determine duration of in vivo survival of CART-HER-2 cells. RT-PCR(reverse transcription polymerase chain reaction)analysis of whole blood will be used to detect and quantify survival of CART-HER-2 TCR zeta:CD137 and TCR(T-cell receptor) zeta cells over time. SECONDARY OBJECTIVES: I.For patients with detectable diseases, measure anti-tumor response due to CART-HER-2 cell infusions. II.Estimate relative trafficking of CART-HER-2 cells in tumor bed. III.Determine if cellular or humoral host immunity develops against the murine anti-HER-2, and assess correlation with loss of detectable CART-HER-2(loss of engraftment). IV.Determine the relative subsets of CART-HER-2 T cells (Tcm,Tem,and Treg). OUTLINE: Patients are assigned to 1 group according to order of enrollment. Patients receive anti-HER-2-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of unacceptable toxicity. After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years. Estimate relative trafficking of CART-HER-2 cells in peripheral blood.
Interventions
BIOLOGICALCART-HER-2
Sponsors
Chinese PLA General Hospital
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
* Chemotherapy refractory HER-2-positive breast cancer, gastric cancer, non-small cell lung cancer, and chemotherapy resistant or relapsed ovary cancer. * Relapsed patients after anti-HER-2 using antibody or kinase inhibitor therapy. * Patients must be 18 years of age or older. * Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2. * Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters: Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter). Total bilirubin \< 1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2). * Seronegative for HIV antibody. * Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. * Patients must be willing to practice birth control during and for four months following treatment.NOTE:women of child-bearing age must have evidence of negative pregnancy test. * Patients must be willing to sign an informed consent.
Exclusion criteria
* Patients with life expectancy less than 12 months will be excluded. * Patients with uncontrolled hypertension (\> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (\> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded. * Patients with any of the following pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), \< 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) \< 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air. * Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded. * Pregnant and/or lactating women will be excluded. * Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors. * Patients with any type of primary immunodeficiencies will be excluded from the study. * Patients requiring corticosteroids (other than inhaled) will be excluded. * Patients with history of T cell tumors will be excluded. * Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Study related adverse events | Until week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Anti-leukemia response to CART-HER-2 cell infusions | up to 24 weeks |
Other
| Measure | Time frame |
|---|---|
| In vivo existence of CART-HER-2 | 1 year |
Countries
China
Contacts
Primary ContactWeidong Han, Dr.
Backup ContactXiru Li, Dr.
Outcome results
None listed