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Multi-4SCAR-T Therapy Targeting Breast Cancer

Primary Purpose

Breast Cancer

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

4SCAR T cells

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring CART, adoptive T cell transfer, Her2, GD2, CD44V6

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with stage III, IV or relapsed breast cancer confirmed by histology and biopsy.
Age: ≥ 18 years and ≤ 75 years.
2 weeks at least since last chemotherapy or radiotherapy and 2 weeks at least since last systemic steroid hormone and other immunosuppressive therapy.
Side effects of chemotherapy have subsided.
The target antigens GD2, CD44v6, or Her2 is expressed in malignancy tissues by immuno-histochemical or flow cytometry.
Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
Expected survival ≥ 12 weeks.
Initial hematopoietic reconstitution with neutrophils (ANC) ≥ 1×10^6/L; platelet (PLT) ≥ 1×10^8/L.
Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with serum creatinine ≤ 2×ULN; serum bilirubin ≤ 3×ULN; AST/ALT ≤ 2.5×ULN.
Oxygen saturation ≥ 90%.
Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

Airway obstruction caused by tumor.
History of epilepsy or other central nervous system diseases.
Patients who require systemic corticosteroid or other immunosuppressive therapy.
History of prolonged or serious heart disease during QT.
Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study.
Inadequate liver and renal function with serum creatinine > 1.5 mg/dl; serum (total) bilirubin > 2.0 mg/dl; AST & ALT > 3 x ULN.
Pregnant or lactating females.
Serious active infection during screening.
Active HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) infection or uncontrolled infection.
Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Sites / Locations

The Seventh Affilliated Hospital, Sun Yat-Sen UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Multiple 4SCAR T cells to treat breast cancer

Arm Description

Multiple 4SCAR T cells to treat breast cancer

Outcomes

Primary Outcome Measures

Number of patients with adverse events.

Determine the toxicity profile the multi-4SCAR-T cells with Common Toxicity Criteria for Adverse Effects version 4.0

Secondary Outcome Measures

Anti-tumor effects

Disease status is defined by the image scan to get the outcomes such as Complete response/remission (CR), Very good partial response/remission (VGPR), etc.

The expansion and persistence of CAR-T cells

The expansion and functional persistence of CART cells in the peripheral blood of patients will be measured by qPCR on Day 7, 14, 21, 28, 60 and 90 after infusion.

Survival time of the patients

The survival time of the patients treated with the multi-4SCAR T cells, including progression free survival (PFS) and overall survival (OS) will be evaluated.

Full Information

NCT ID

NCT04430595

First Posted

June 9, 2020

Last Updated

June 10, 2020

Sponsor

Shenzhen Geno-Immune Medical Institute

Collaborators

The Seventh Affiliated Hospital of Sun Yat-sen University

1. Study Identification

Unique Protocol Identification Number

NCT04430595

Brief Title

Multi-4SCAR-T Therapy Targeting Breast Cancer

Official Title

Multiple 4SCAR-T Cell Therapy Targeting Breast Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Recruiting

Study Start Date

June 1, 2020 (Anticipated)

Primary Completion Date

May 31, 2023 (Anticipated)

Study Completion Date

December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shenzhen Geno-Immune Medical Institute

Collaborators

The Seventh Affiliated Hospital of Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to assess the feasibility, safety and efficacy of multiple 4th generation CAR-T cells targeting Her2, GD2, and CD44v6 surface antigen in breast cancer. Another goal of the study is to learn more about the activities of the multi-CAR T cells and their persistency in the patients.

Detailed Description

Breast cancer is one of the most frequent cancer types in women. The average risk of a woman in the United States developing breast cancer in her life is about 13%. That means that there is a 1 in 8 chance she will develop breast cancer. Human epidermal growth factor receptor-2 (HER2) is one of the more well-researched genes in breast cancer so far. It has been reported that HER2 gene is overexpressed in 20% to 30% of breast cancer patients. HER2 is an important target for tumor gene therapy. In 2003, scientists confirmed the existence of breast cancer stem cells. In 2012, ganglioside GD2 was confirmed as an emerging marker of breast cancer stem cells. Targeting therapies for GD2 may help improve the survival rate and cure rate of breast cancer patients. Invasion and metastasis of tumor cells is the main cause of cancer death. CD44v6 is an adhesion molecule on the cell surface, which not only promotes epithelial-mesenchymal transition, degradation and remodeling of extracellular matrix, but also participates in organ-specific metastasis of tumor cells. Studies have shown that overexpression of CD44v6 is an important factor for the invasion and metastasis of breast cancer, and is closely related to the tumor size of the breast cancer, tumor staging, and lymph node metastasis. Therefore, CD44v6 may be an important target for the treatment of breast cancer. Using Her2-, GD2- and CD44v6-specific CAR-T cells may effectively improve the immunotherapy treatment, prevent tumor cells from escaping treatment, and achieve the effect of long-term disease relief.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

CART, adoptive T cell transfer, Her2, GD2, CD44V6

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Multiple 4SCAR T cells to treat breast cancer

Arm Type

Experimental

Arm Description

Multiple 4SCAR T cells to treat breast cancer

Intervention Type

Biological

Intervention Name(s)

4SCAR T cells

Intervention Description

Infusion of 4SCAR-GD2, -Her2 and -CD44v6 CAR-T cells

Primary Outcome Measure Information:

Title

Number of patients with adverse events.

Description

Determine the toxicity profile the multi-4SCAR-T cells with Common Toxicity Criteria for Adverse Effects version 4.0

Time Frame

3 year

Secondary Outcome Measure Information:

Title

Anti-tumor effects

Description

Disease status is defined by the image scan to get the outcomes such as Complete response/remission (CR), Very good partial response/remission (VGPR), etc.

Time Frame

3 year

Title

The expansion and persistence of CAR-T cells

Description

The expansion and functional persistence of CART cells in the peripheral blood of patients will be measured by qPCR on Day 7, 14, 21, 28, 60 and 90 after infusion.

Time Frame

3 months

Title

Survival time of the patients

Description

The survival time of the patients treated with the multi-4SCAR T cells, including progression free survival (PFS) and overall survival (OS) will be evaluated.

Time Frame

3 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with stage III, IV or relapsed breast cancer confirmed by histology and biopsy. Age: ≥ 18 years and ≤ 75 years. 2 weeks at least since last chemotherapy or radiotherapy and 2 weeks at least since last systemic steroid hormone and other immunosuppressive therapy. Side effects of chemotherapy have subsided. The target antigens GD2, CD44v6, or Her2 is expressed in malignancy tissues by immuno-histochemical or flow cytometry. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1. Expected survival ≥ 12 weeks. Initial hematopoietic reconstitution with neutrophils (ANC) ≥ 1×10^6/L; platelet (PLT) ≥ 1×10^8/L. Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with serum creatinine ≤ 2×ULN; serum bilirubin ≤ 3×ULN; AST/ALT ≤ 2.5×ULN. Oxygen saturation ≥ 90%. Written, informed consent obtained prior to any study-specific procedures. Exclusion Criteria: Airway obstruction caused by tumor. History of epilepsy or other central nervous system diseases. Patients who require systemic corticosteroid or other immunosuppressive therapy. History of prolonged or serious heart disease during QT. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study. Inadequate liver and renal function with serum creatinine > 1.5 mg/dl; serum (total) bilirubin > 2.0 mg/dl; AST & ALT > 3 x ULN. Pregnant or lactating females. Serious active infection during screening. Active HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) infection or uncontrolled infection. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lung-Ji Chang, PhD

Phone

+86(755)8672 5195

c@szgimi.org

Facility Information:

Facility Name

The Seventh Affilliated Hospital, Sun Yat-Sen University

City

Shenzhen

State/Province

Guangdong

ZIP/Postal Code

518107

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Bo Wang, MD

Phone

86-0755-23242570

wangb68377@sina.com

12. IPD Sharing Statement

Plan to Share IPD

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Multi-4SCAR-T Therapy Targeting Breast Cancer

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