EGFR-IL12-CART Cells for Patients With Metastatic Colorectal Cancer (EGFRCART)

Phase I/II Study of EGFR-IL12-CART Cells for Patients With Metastatic Colorectal Cancer

This is a clinical study to observe the maximum tolerated dose (MTD) and the safety and feasibility of chimeric antigen receptor EGFR (EGFR -IL12 -CART) cells in metastatic patients with colorectal cancer.

Study Overview

• Status: Unknown
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Biological: EGFR IL12 CART

Detailed Description

This is a study for the patients with colorectal cancer. Maximum tolerated dose climbing test is expected into the group of 9 cases of patients. And Phase II expected into the group of 11 subjects, selected the above safe dose, carrying out a research into the clinical effectiveness. Subjects will be collected their T cells and modify them, the modification is a genetic change, that EGFR:4-1BB:CD28:CD3 modified T cells, in order to tells the T cells to recognize their target tumor cells and potentially kill them, but not other normal cells in the subject's body. The CART cells will then be expanded in vitro and then administered to subjects. Fourth generation CART, also known as TRUCKs (T cells redirected for universal cytokine before), mainly in order to improve the effect of solid tumor treatment and design, through NFAT transcription factors inducing expression of IL - 12, overcome the solid tumor within the tumor microenvironment of CART limit the function of cellsThe purpose of this study is observe the MTD and to assess the safety and feasibility of CART cells in the patients with metastatic colorectal cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • GuangGong
    • Shenzhen, GuangGong, China
      • Geng Tian 13724395569 Tiangeng666@Aliyun.Com
      • Contact: geng tian, DOCTOR; Phone Number: 13724395569; Email: tiangeng666@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must be 18 years to 70 years;
2. Clinical diagnosis of EGFR positive for patients with metastatic colorectal cancer;
3. Patients must have a KPS of >80, expected survival > 3 months;
4. Patients must have at least one measurable lesions;
5. Recently did not use glucocorticoid;
6. Patients must have evidence of adequate hepatic and renal function as evidenced by the following laboratory parameters: WBC ≥ 3.0×109/L, Hb ≥90 g/L, PLT ≥100×109/L）; AST ≤2.5ULN，ALT ≤ 2.5ULN; Cr≤ 3ULN; TBIL≤ 3ULN，
7. Patients must have a good heart function (LVEF>50%) ;
8. Patients must be willing to practice birth control during and for three months following treatment.NOTE:female participants of reproductive potential must have a negative serum pregnancy test, and willing to practice birth control during and for three months following treatment；
9. Patients must be willing to sign an informed consent.

Exclusion Criteria:

1. Patients with other cancer history;
2. Patients allergic to cetuximab;
3. Patients with severe bronchitis, bronchial asthma, or severs pneumonia;
4. Patients with uncontrolled active infections (bacteria, viruses or fungi infection) ;
5. Patients with acute and chronic GVHD (graft versus host disease)
6. Patients with severe autoimmune diseases;
7. Previously treatment with T cell inhibitors (cyclophosphamide, FK506);
8. Patients with active hepatitis B or hepatitis C infection, HIV infection, syphilis serology reaction positive;
9. Patients who are participating or participated any other clinical research in the past 1 months;
10. Pregnant and/or lactating women will be excluded; -

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: 3; anti-tumor response of EGFR IL12 CART	Biological: EGFR IL12 CART; EGFR IL12 CART cells will be administered using a split dose on day0 (10%),1(30%), and 2(60%)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Occurrence of study related adverse events	Occurrence of study related adverse events as assessed by CTCAE v4.0	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness: Changes of tumor markers	Changes of tumor markers CA-199, AFP and CEA	24 weeks
Effectiveness: duration of in vivo survival of EGFR CART	Determine duration of in vivo survival of EGFR CART	1 year

Collaborators and Investigators

• Sponsor: Shenzhen Second People's Hospital
• Collaborators: The Pregene (ShenZhen) Biotechnology Company, Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 22, 2018
• Primary Completion (Anticipated): May 23, 2020
• Study Completion (Anticipated): May 23, 2021

Study Registration Dates

• First Submitted: May 18, 2018
• First Submitted That Met QC Criteria: May 30, 2018
• First Posted (Actual): May 31, 2018

Study Record Updates

• Last Update Posted (Actual): May 31, 2018
• Last Update Submitted That Met QC Criteria: May 30, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: Protocol. PGCAR/EGFR012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No