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

• ClinicalTrials.gov Identifier: NCT03542799
• Recruitment Status: Unknown
• First Posted: May 31, 2018
• Last Update Posted: May 31, 2018
• Sponsor: Shenzhen Second People's Hospital
• Collaborator: The Pregene (ShenZhen) Biotechnology Company, Ltd.
• Information provided by (Responsible Party): tiangeng, Shenzhen Second People's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Colorectal Cancer	Biological: EGFR IL12 CART	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of EGFR-IL12-CART Cells for Patients With Metastatic Colorectal Cancer
• Estimated Study Start Date: May 22, 2018
• Estimated Primary Completion Date: May 23, 2020
• Estimated Study Completion Date: May 23, 2021

Arms and Interventions

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%)

Outcome Measures

Primary Outcome Measures :

1. Safety: Occurrence of study related adverse events [ Time Frame: 24 weeks ]
   Occurrence of study related adverse events as assessed by CTCAE v4.0

Secondary Outcome Measures :

1. Effectiveness: Changes of tumor markers [ Time Frame: 24 weeks ]
   Changes of tumor markers CA-199, AFP and CEA
2. Effectiveness: duration of in vivo survival of EGFR CART [ Time Frame: 1 year ]
   Determine duration of in vivo survival of EGFR CART

Eligibility Criteria

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

Criteria

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; -

Contacts and Locations

Locations

China, GuangGong

Geng Tian 13724395569 Tiangeng666@Aliyun.Com

Shenzhen, GuangGong, China

Contact: geng tian, DOCTOR 13724395569 tiangeng666@aliyun.com

Sponsors and Collaborators

Shenzhen Second People's Hospital

The Pregene (ShenZhen) Biotechnology Company, Ltd.

More Information

• Responsible Party: tiangeng, Chief physician, Shenzhen Second People's Hospital
• ClinicalTrials.gov Identifier: NCT03542799
• Other Study ID Numbers: Protocol. PGCAR/EGFR012
• First Posted: May 31, 2018
• Last Update Posted: May 31, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases