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

Phase 1

• Conditions: Advanced HER-2 Positive Solid Tumors; Chemotherapy Refactory; HER-2 Antibody Inhibitor Therapy Refactory
• Interventions: Biological: CART-HER-2

• Registration Number: NCT01935843
• Lead Sponsor: Chinese PLA General Hospital

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.

Study Timeline

• Study Start: 2013-09
• Study First Submitted: 2013-09-01
• Study First Submitted QC: 2013-09-01
• Study First Posted: 2013-09-05
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-26
• Last Update Posted: 2016-01-28
• Primary Completion: 2016-09
• Study Completion: 2017-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Anti-tumor responses of CART-HER-2	CART-HER-2	-

Primary Outcome Measures

Name	Time	Method
Occurrence of Study related adverse events	Until week 24

Secondary Outcome Measures

Name	Time	Method
Anti-leukemia response to CART-HER-2 cell infusions	up to 24 weeks

Trial Locations

Locations (1)

Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China