A Clinical Research of CAR T Cells Targeting HER2 Positive Cancer

Chimeric antigen receptor T cells (CAR-T) therapy has not yet been fully explored in solid tumors. Human epidermal growth factor receptor-2(HER2) is widely expressed in cancers. Investigators have developed anti-HER2 CAR-modified T cells and validated the efficiency targeting HER2-positive cancer in preclinical studies. This study is aimed to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, CAR-T cells persistence, tumor elimination and disease status after treatment will be evaluated.

Study Overview

• Status: Withdrawn
• Conditions: Glioma; Breast Cancer; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Ovarian Cancer; Lung Cancer
• Intervention / Treatment: Biological: Anti-HER2 CAR-T

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Southwest Hospital of Third Millitary Medical University

Participation Criteria

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:

1. Relapsed or refractory HER2 positive cancer.
2. KPS>60.
3. Life expectancy>3 months.
4. Gender unlimited, age from 18 years to 80 years.
5. Assessable lesions with a minimum size of 10mm by CT scan or MRI.

6. Acceptable organ function

   Hematology:

   • Absolute neutrophil count greater than 800/mm^3 without the support of filgrastim.
   • White blood cell (WBC) (> 2000/mm^3).
   • Platelet count greater than 50,000/mm^3.
   • Hemoglobin greater than 9.0 g/dl.

   Chemistry:

   • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 3 times the upper limit of normal (patients without liver metastasis) or 6 times the upper limit of normal (patients with liver metastasis).
   • Serum creatinine less or equal to 3 times the upper limit of normal
   • Total bilirubin less than or equal to 3 times the upper limit of normal.
7. No other serious diseases(autoimmune disease, immunodeficiency etc.).
8. Adequate cardiac function(LVEF≥40%).
9. No other tumors.
10. Patients volunteer to participate in the research.

Exclusion Criteria:

1. Allergic to cytokines.
2. Uncontrolled active infection.
3. Acute or chronic GVHD.
4. MODS.
5. Treated with T cell inhibitor.
6. HIV affected.
7. Other situations improper for the research.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HER2 positive cancers; Patients with relapsed and refractory cancer of HER2 expression will be treated with anti-HER2 CAR-T cells	Biological: Anti-HER2 CAR-T; HER-2-targeting CAR-T cells infusion in HER2 positive cancers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the toxicity profile of the HER2 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.	Observe and handle the toxicity profile of the HER2 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival time of Anti-HER2 CAR T cells in vivo.	Detect the existence of CAR-T cells in the blood of participants through qPCR or flow cytometry.	1 year
Efficacy of anti-HER2 CAR T cells to confirm the ability of CAR T cells to eliminate HER2 positive cancer cells	Evaluate the anti-tumor efficacy of CAR-T therapy by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and Immune-Related Response Criteria（iRECIST）.	12 weeks
Maximum tolerated dose (MTD) of HER2 targeted CAR T cells	Determine the maximum tolerated dose of each participant through the grades of side effects.	4 weeks

Collaborators and Investigators

• Sponsor: Zhi Yang
• Investigators: Principal Investigator: Cheng Qian, MD,PhD, Southwest Hospital, China

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): July 1, 2019
• Study Completion (Actual): July 1, 2019

Study Registration Dates

• First Submitted: March 12, 2016
• First Submitted That Met QC Criteria: March 18, 2016
• First Posted (Estimate): March 21, 2016

Study Record Updates

• Last Update Posted (Actual): March 19, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: safety; efficiency; HER2 CAR-T; refractory and relapsed cancer
• Other Study ID Numbers: TMMU-BTC-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided