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Treatment of Chemotherapy Refractory EGFR(Epidermal Growth Factor Receptor) Positive Advanced Solid Tumors (CART-EGFR) (CART-EGFR)

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ClinicalTrials.gov Identifier: NCT01869166
Recruitment Status : Unknown
Verified September 2015 by Han weidong, Chinese PLA General Hospital.
Recruitment status was:  Recruiting
First Posted : June 5, 2013
Last Update Posted : September 29, 2015
Sponsor:
Information provided by (Responsible Party):
Han weidong, Chinese PLA General Hospital

Tracking Information
First Submitted Date  ICMJE June 1, 2013
First Posted Date  ICMJE June 5, 2013
Last Update Posted Date September 29, 2015
Study Start Date  ICMJE May 2013
Estimated Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2013)
Occurrence of study related adverse events [ Time Frame: Until week 24 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01869166 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2015)
Anti-tumor responses to CART-EGFR cell infusions [ Time Frame: up to 24 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2013)
Anti-leukemia responses to CART-EGFR cell infusions [ Time Frame: up to 24 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: June 1, 2013)
in vivo existence of CART-EGFR [ Time Frame: 1 year ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Treatment of Chemotherapy Refractory EGFR(Epidermal Growth Factor Receptor) Positive Advanced Solid Tumors (CART-EGFR)
Official Title  ICMJE Clinical Study of Chimeric EGFR Antigen Receptor-modified T Cells in Chemotherapy Refractory Advanced Solid Tumors
Brief Summary

RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous T cells may make the body build immune response to kill cancer cells.

PURPOSE: This clinical trial is to study genetically engineered lymphocyte therapy in treating patients with EGFR positive advanced/unresectable operation solid tumors, such as lung cancer, colorectal cancer,ovary cancer,cholangiocarcinoma,pancreatic cancer,renal carcinoma and other relapsed/metastatic tumors.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-EGFR Lentivirus vector (referred to as CART-EGFR cells).

II. Determine duration of in vivo survival of CART-EGFR cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-EGFR CD3zeta:CD137 over time.

SECONDARY OBJECTIVES:

I. For patients with advanced, relapsed/metastatic cancers, measure anti-tumor response due to CART-EGFR cell infusions.

II. Estimate relative trafficking of CART-EGFR cells in tumor bed.

III. Determine if cellular or humoral host immunity develops against the murine anti-EGFR, and assess correlation with loss of detectable CART-EGFR (loss of engraftment).

IV. Determine the relative subsets of CART-EGFR T cells (Tcm, Tem, and Treg).

OUTLINE: Patients are assigned to 1 group according to order of enrollment.

Patients receive anti-EGFR-CAR (coupled with CD137 and CD3 zeta signalling domains)Lentivirus vector-transduced autologous T cells for 3-5 days in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.

Estimate relative trafficking of CART-EGFR cells in peripheral blood.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced EGFR-positive Solid Tumors
Intervention  ICMJE Biological: CART-EGFR
Study Arms  ICMJE Experimental: anti-tumor response of CART-EGFR
Intervention: Biological: CART-EGFR
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 27, 2015)
60
Original Estimated Enrollment  ICMJE
 (submitted: June 1, 2013)
10
Estimated Study Completion Date  ICMJE December 2017
Estimated Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Chemotherapy refractory EGFR-positive non-small cell lung cancer, colorectal cancer with liver metastasis,and chemotherapy resistant or relapsed ovary cancerlung cancer,cholangiocarcinoma,pancreatic cancer,renal carcinoma and other relapsed/metastatic/unresectable operation tumors.the expression of EGFR in tumor is more than 50%.
  2. Relapsed patients after anti-EGFR using antibody or kinase inhibitor therapy.
  3. Patients must be 18 years of age or older.
  4. Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2.
  5. Patients must have evidence of adequate hepatic and renal function as evidenced by the following laboratory parameters:

    Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter).

    Total bilirubin < 1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2).

  6. Seronegative for HIV antibody.
  7. Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.
  8. Patients must be willing to practice birth control during and for four months following treatment.NOTE:women of child-bearing age must have evidence of negative pregnancy test.
  9. Patients must be willing to sign an informed consent.

Exclusion Criteria:

  1. Patients with life expectancy less than 12 months will be excluded.
  2. Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded.
  3. Patients with any of the following pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), < 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air.
  4. Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded.
  5. Pregnant and/or lactating women will be excluded.
  6. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.
  7. Patients with any type of primary immunodeficiencies will be excluded from the study.
  8. Patients requiring corticosteroids (other than inhaled) will be excluded.
  9. Patients with history of T cell tumors will be excluded.
  10. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01869166
Other Study ID Numbers  ICMJE CHN-PLAGH-BT-007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Han weidong, Chinese PLA General Hospital
Study Sponsor  ICMJE Chinese PLA General Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: weidong han, Dr. Chinese PLA General Hospital
PRS Account Chinese PLA General Hospital
Verification Date September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP