NCT03081715

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
16

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Mar 2017

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 11, 2017

Completed
3 days until next milestone

Study Start

First participant enrolled

March 14, 2017

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 16, 2017

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 23, 2018

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2018

Completed
Last Updated

June 12, 2019

Status Verified

June 1, 2019

Enrollment Period

11 months

First QC Date

March 11, 2017

Last Update Submit

June 10, 2019

Conditions

Esophageal Cancer

Keywords

esophageal cancerimmune checkpointPD-1CRISPERautologous cell infusion

Outcome Measures

Primary Outcomes (1)

  • Response Rate

    Response will be evaluated according to RECIST v1.1

    1-3 months

Secondary Outcomes (1)

  • Incidence of Treatment-Emergent Adverse Events

    6 months

Other Outcomes (4)

  • Progression free survival (PFS)

    1 year

  • Overall Survival (OS)

    1 year

  • Peripheral blood T lymphocyte subsets

    6 weeks

  • +1 more other outcomes

Study Arms (1)

Experimental Group

EXPERIMENTAL

Peripheral blood lymphocytes will be collected and Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9 in the laboratory (PD-1 Knockout T cells). The lymphocytes will be selected and expanded ex vivo and reinfused back into patients. To avoid allergic reactions, 50 mg hydrocortisone was intravenously injected into the patient 30 min before cells infusion every time. Best supportive care was also provided for patients. A total of 1 to 10 x 10\^9 PD-1 Knockout T cells will be infused each cycle. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT or they withdrew consent.

Other: PD-1 Knockout T Cells

Interventions

PD-1 Knockout T CellsOTHER

Programmed cell death 1(PD-1) gene will be knocked out by CRISPR Cas9

Experimental Group

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hangzhou Cancer Hospital

Hangzhou, Zhejiang, 310002, China

Location

Related Publications (3)

  • 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.

    PMID: 24486104BACKGROUND

  • 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.

    PMID: 25838374BACKGROUND

  • 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.

    PMID: 25860605BACKGROUND

MeSH Terms

Conditions

Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Study Officials

  • shixiu wu, Professor

    Hangzhou Cancer Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Masking Details
open-label
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

March 11, 2017

First Posted

March 16, 2017

Study Start

March 14, 2017

Primary Completion

January 23, 2018

Study Completion

February 28, 2018

Last Updated

June 12, 2019

Record last verified: 2019-06

Locations

CN(1)