Clinical trial NCT01935843: Treatment of Chemotherapy Refractory Human Epidermalgrowth Factor Receptor-2( HER-2) Positive Advanced Solid Tumors
Official title: Clinical Study of Chimeric HER-2 Antigen Receptor-modified T Cells in Chemotherapy Refractory HER-2 Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced HER-2 Positive Solid Tumors
Chemotherapy Refactory
HER-2 Antibody Inhibitor Therapy Refactory
Keywords: CART-HER-2
HER-2 positive
Advanced
Refactory
Solid tumors
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2013-09-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of Study related adverse events
timeFrame: Until week 24
Secondary outcomes:
measure: Anti-leukemia response to CART-HER-2 cell infusions
timeFrame: up to 24 weeks
Other outcomes:
measure: In vivo existence of CART-HER-2
timeFrame: 1 year
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Weidong Han, Dr.
role: STUDY_CHAIR
References:
citation: Feng K, Liu Y, Guo Y, Qiu J, Wu Z, Dai H, Yang Q, Wang Y, Han W. Phase I study of chimeric antigen receptor modified T cells in treating HER2-positive advanced biliary tract cancers and pancreatic cancers. Protein Cell. 2018 Oct;9(10):838-847. doi: 10.1007/s13238-017-0440-4. Epub 2017 Jul 14.