A Clinical Research of CAR T Cells Targeting HER2 Positive Cancer

Phase 1

Withdrawn

• Conditions: Ovarian Cancer; Breast Cancer; Lung Cancer; Pancreatic Cancer; Colorectal Cancer; Gastric Cancer; Glioma
• Interventions: Biological: Anti-HER2 CAR-T

• Registration Number: NCT02713984
• Lead Sponsor: Zhi Yang

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-03
• Study First Submitted: 2016-03-12
• Study First Submitted QC: 2016-03-18
• Study First Posted: 2016-03-21
• Primary Completion: 2019-07
• Study Completion: 2019-07
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-17
• Last Update Posted: 2020-03-19

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HER2 positive cancers	Anti-HER2 CAR-T	Patients with relapsed and refractory cancer of HER2 expression will be treated with anti-HER2 CAR-T cells

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Efficacy of anti-HER2 CAR T cells to confirm the ability of CAR T cells to eliminate HER2 positive cancer cells	12 weeks	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）.
Maximum tolerated dose (MTD) of HER2 targeted CAR T cells	4 weeks	Determine the maximum tolerated dose of each participant through the grades of side effects.
Survival time of Anti-HER2 CAR T cells in vivo.	1 year	Detect the existence of CAR-T cells in the blood of participants through qPCR or flow cytometry.

Trial Locations

Locations (1)

Southwest Hospital of Third Millitary Medical University; 🇨🇳 Chongqing, Chongqing, China