CART-HER-2: Treatment of Chemotherapy Refractory Human Epidermalgrowth Factor Receptor-2( HER-2) Positive Advanced Solid Tumors

Sponsor

Chinese PLA General Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT01935843

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced HER-2 Positive Solid Tumors Chemotherapy Refactory HER-2 Antibody Inhibitor Therapy Refactory	Biological: CART-HER-2	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Clinical Study of Chimeric HER-2 Antigen Receptor-modified T Cells in Chemotherapy Refractory HER-2 Advanced Solid Tumors

Study Start Date :

Sep 1, 2013

Anticipated Primary Completion Date :

Sep 1, 2016

Anticipated Study Completion Date :

Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anti-tumor responses of CART-HER-2	Biological: CART-HER-2

Arm

Intervention/Treatment

Experimental: Anti-tumor responses of CART-HER-2

Biological: CART-HER-2

Outcome Measures

Primary Outcome Measures

Occurrence of Study related adverse events [Until week 24]

Secondary Outcome Measures

Anti-leukemia response to CART-HER-2 cell infusions [up to 24 weeks]

Other Outcome Measures

In vivo existence of CART-HER-2 [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.