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

January 26, 2016 updated by: Han weidong, Chinese PLA General Hospital

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100853
        • Recruiting
        • Chinese PLA General Hospital
        • Principal Investigator:
          • Yao Wang, Dr.
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Occurrence of Study related adverse events
Time Frame: Until week 24
Until week 24

Secondary Outcome Measures

Outcome Measure
Time Frame
Anti-leukemia response to CART-HER-2 cell infusions
Time Frame: up to 24 weeks
up to 24 weeks

Other Outcome Measures

Outcome Measure
Time Frame
In vivo existence of CART-HER-2
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese PLA General Hospital

Investigators

  • Study Chair: Weidong Han, Dr., Chinese PLA General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Anticipated)

September 1, 2016

Study Completion (Anticipated)

September 1, 2017

Study Registration Dates

First Submitted

September 1, 2013

First Submitted That Met QC Criteria

September 1, 2013

First Posted (Estimate)

September 5, 2013

Study Record Updates

Last Update Posted (Estimate)

January 28, 2016

Last Update Submitted That Met QC Criteria

January 26, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHN-PLAGH-BT-009

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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