Evaluate the Safety and Efficacy of CAR-T in the Treatment of Pancreatic Cancer.

NCT ID: NCT03267173

Last Updated: 2017-08-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-15
• Study Completion Date: 2019-06-30

Brief Summary

Immunotherapy has become the major breakthrough and the most promising treatment, with the host of development of tumor biology, molecular biology and immunology. It has become the fourth tumor treatment model after traditional tumor therapies (surgery, chemotherapy, radiotherapy) . Mesothelin, PSCA, CEA, HER2, MUC1 and EGFRvIII are potential targets and spectacular paradigm in the diagnosis and treatment of pancreatic cancer. This study is for evaluation of the safety and efficacy of Mesothelin, PSCA, CEA, HER2, MUC1, EGFRvIII targeted and other CAR-T cell immunotherapy for pancreatic cancer.

Detailed Description

Immunotherapy has become the major breakthrough and the most promising treatment, with the host of development of tumor biology, molecular biology and immunology. It has become the fourth tumor treatment model after traditional tumor therapies (surgery, chemotherapy, radiotherapy) . With the development of the research field, the CAR-T cell basis and clinical research of various targets have achieved good results. Mesothelin, PSCA, CEA, HER2, MUC1 and EGFRvIII are potential targets and spectacular paradigm in the diagnosis and treatment of pancreatic cancer. This study is for evaluation of the safety and efficacy of Mesothelin, PSCA, CEA, HER2, MUC1, EGFRvIII targeted and other CAR-T cell immunotherapy for pancreatic cancer.

Conditions

Pancreatic Cancer; CAR

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAR-T

A single dose of Chimeric antigen receptor T cells will be administered by vascular interventional mediated as one dose infusions. According to the patient's condition and weight, the intervention dose of aE7 CAR-T cells per kilogram of body weight was treated once.

Group Type: EXPERIMENTAL

Chimeric antigen receptor T cell

Intervention Type: DRUG

Evaluate the efficacy and safety of targeted Mesothelin/PSCA/CEA/HER2/MUC1/, EGFRvIII and other chimeric antigen receptor engineered T cell immunotherapy in the treatment of pancreatic cancer.

Interventions

Chimeric antigen receptor T cell

Evaluate the efficacy and safety of targeted Mesothelin/PSCA/CEA/HER2/MUC1/, EGFRvIII and other chimeric antigen receptor engineered T cell immunotherapy in the treatment of pancreatic cancer.

Intervention Type: DRUG

Other Intervention Names

meso-CAR

Eligibility Criteria

Inclusion Criteria

• Imaging, pathology or biopsy confirmed as pancreatic cancer and it has metastasized, can not radical cured by surgery; patients restored good but there is still residual lesions, recurrence or metastasis 1 months after surgery;
• Accepted more than 1 times chemotherapy which is invalid or unwilling to accept previous chemotherapy patients;
• The corresponding antigens such as Meso and PSCA/ CEA/ HER2/ MUC1/ EGFRvIII were highly expressed;
• Male patients aged between 18 and 65;
• Life expectancy greater than 1 months;
• Karnofsky score ≥ 60, ECOG≤ 2;
• Important organ function as defined by the following: cardiac ejection fraction ≥ 50%; electrocardiogram showed no obvious abnormalities; creatinine clearance rate calculated by using Cockcroft- Gault formula ≥40ml/min ; ALT/AST≤ 3×the institution normal upper limit; total bilirubin ≤2.0mg/dl; coagulation function: PT/ APPT<2 ×the institution normal upper limit; SpO2 >92%; Blood: hemoglobin>80g/L, ANC ≥ 1, PLT ≥ 50×109/L;
• There is measurable target lesion;
• Voluntary informed consent is given.

Exclusion Criteria

• Immunosuppressive drugs or hormones were used a week before admission;
• Severe active infection;
• Human immunodeficiency virus (HIV) positive;
• Active hepatitis B or C infection;
• Past medical history of other malignancies. Not included: patients who have been cured at any time prior to the treatment of the skin basal or squamous cell carcinoma and cervical carcinoma in situ; the other tumor has not listed above, but has been used and only cured by surgery, without further treatment by other measures, the subjects of disease-free survival more than 5 years, can be included in the study;
• Patients participating in other clinical trials;
• The researchers thought the subjects were unfit for inclusion or unable to participate in or complete the study；
• Patients with congenital immunodeficiency；
• There is a history of myocardial infarction and serious arrhythmia within six months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

INDUSTRY

Sponsor Role: collaborator

First Affiliated Hospital of Harbin Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wei Yunwei, Dctor

Role: STUDY_DIRECTOR

First Affiliated Hospital of Harbin Medical University

Locations

Harbin Medical University

Harbin, Heilongjiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wei Yunwei, Dctor

Role: CONTACT

hydwyw11@hotmall.com

86-85553099

Zhao Lei, Dctor

Role: CONTACT

zhaoleihyd@163.com

86-13069890888

Facility Contacts

Zhao Lei, Doctor

Role: primary

zhaoleihyd@163.com

86-13069890888

References

Zervos E, Agle S, Freistaedter AG, Jones GJ, Roper RL. Murine mesothelin: characterization, expression, and inhibition of tumor growth in a murine model of pancreatic cancer. J Exp Clin Cancer Res. 2016 Mar 1;35:39. doi: 10.1186/s13046-016-0314-2.

Reference Type: BACKGROUND

PMID: 26931187 (View on PubMed)

Freedman JD, Hagel J, Scott EM, Psallidas I, Gupta A, Spiers L, Miller P, Kanellakis N, Ashfield R, Fisher KD, Duffy MR, Seymour LW. Oncolytic adenovirus expressing bispecific antibody targets T-cell cytotoxicity in cancer biopsies. EMBO Mol Med. 2017 Aug;9(8):1067-1087. doi: 10.15252/emmm.201707567.

Reference Type: BACKGROUND

PMID: 28634161 (View on PubMed)

Morello A, Sadelain M, Adusumilli PS. Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors. Cancer Discov. 2016 Feb;6(2):133-46. doi: 10.1158/2159-8290.CD-15-0583. Epub 2015 Oct 26.

Reference Type: BACKGROUND

PMID: 26503962 (View on PubMed)

Le DT, Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, Morse M, Zeh H, Cohen D, Fine RL, Onners B, Uram JN, Laheru DA, Lutz ER, Solt S, Murphy AL, Skoble J, Lemmens E, Grous J, Dubensky T Jr, Brockstedt DG, Jaffee EM. Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol. 2015 Apr 20;33(12):1325-33. doi: 10.1200/JCO.2014.57.4244. Epub 2015 Jan 12.

Reference Type: BACKGROUND

PMID: 25584002 (View on PubMed)

Abate-Daga D, Lagisetty KH, Tran E, Zheng Z, Gattinoni L, Yu Z, Burns WR, Miermont AM, Teper Y, Rudloff U, Restifo NP, Feldman SA, Rosenberg SA, Morgan RA. A novel chimeric antigen receptor against prostate stem cell antigen mediates tumor destruction in a humanized mouse model of pancreatic cancer. Hum Gene Ther. 2014 Dec;25(12):1003-12. doi: 10.1089/hum.2013.209.

Reference Type: BACKGROUND

PMID: 24694017 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov

References are all derived from PubMed

Other Identifiers

Yunwei Wei

Identifier Type: -

Identifier Source: org_study_id