Clinical trial NCT03081715: PD-1 Knockout Engineered T Cells for Advanced Esophageal Cancer
Official title: Safety and Activity of Programmed Cell Death-1 Knockout Engineered T Cells in Patients With Previously Treated Advanced Esophageal Squamous Cell Carcinoma: An Open-label, Single-arm Phase 1 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Esophageal Cancer
Keywords: esophageal cancer
immune checkpoint
PD-1
CRISPER
autologous cell infusion
Lead sponsor: Hangzhou Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Anhui Kedgene Biotechnology Co.,Ltd
First posted: 2017-03-16
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety of PD-1 knockout engineered T cells in treating advanced esophageal cancer. Blood or tissue samples will also be collected for research purposes.

Detailed description: This is a prospective clinical study of ex-vivo selected, engineered, and expanded PD-1 knockout T cells from autologous origin. 16 advanced esophageal cancer patients are planned to receive two cycles of PD-1 knockout engineered T cells infusion. Immunological markers are analyzed as well.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed recurrent or metastatic esophageal cancer
* Measurable disease
* Progressed after standard treatments
* ECOG performance status of 0-2
* Expected life span: \>= 3 months
* Toxicities from prior treatment has resolved or ≤ grade 1
* Major organs function normally
* Women at pregnant ages should be under contraception
* Willing and able to provide informed consent

Exclusion Criteria:

* Other malignancy within 5 years prior to entry into the study, expect for treated non-melanoma skin cancer and cervical carcinoma in situ
* Poor vasculature
* Disease to the central nervous system
* Blood-borne infectious disease, e.g. hepatitis B
* History of mandatory custody because of psychosis or other psychological disease inappropriate for treatment deemed by treating physician
* With other immune diseases, or chronic use of immunosuppressants or steroids
* Pregnancy (women of childbearing potential:Refusal or inability to use effective means of contraception)
* Breastfeeding
* Decision of unsuitableness by principal investigator or physician-in-charge

Primary outcomes:
measure: Response Rate
timeFrame: 1-3 months
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 6 months
Other outcomes:
measure: Progression free survival (PFS)
timeFrame: 1 year
measure: Overall Survival (OS)
timeFrame: 1 year
measure: Peripheral blood T lymphocyte subsets
timeFrame: 6 weeks
measure: Tumor-infiltrating T cells
timeFrame: Baseline and after treatment
Locations:
city: Hangzhou
country: China
facility: Hangzhou Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Hangzhou Cancer Hospital
name: shixiu wu, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Niu Y, Shen B, Cui Y, Chen Y, Wang J, Wang L, Kang Y, Zhao X, Si W, Li W, Xiang AP, Zhou J, Guo X, Bi Y, Si C, Hu B, Dong G, Wang H, Zhou Z, Li T, Tan T, Pu X, Wang F, Ji S, Zhou Q, Huang X, Ji W, Sha J. Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell. 2014 Feb 13;156(4):836-43. doi: 10.1016/j.cell.2014.01.027. Epub 2014 Jan 30.
citation: Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015 Apr 3;348(6230):62-8. doi: 10.1126/science.aaa4967.
citation: Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015 Apr 9;161(2):205-14. doi: 10.1016/j.cell.2015.03.030.