HPV-E6-Specific Anti-PD1 TCR-T Cells in the Treatment of HPV-Positive NHSCC or Cervical Cancer
Primary Purpose
Cervical Cancer, Head and Neck Squamous Cell Carcinoma
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HPV E6-specific TCR-T cells
Sponsored by
About this trial
This is an interventional treatment trial for Cervical Cancer
Eligibility Criteria
Inclusion Criteria:
- Expected to live longer than 12 weeks
- PS 0-2
- Pathology confirmed as HPV16 positive malignant tumor, either metastatic or recurrent disease
- Creatinine <2.5mg/dl
- ALT/AST is lower than three times ULN.
- No contraindications of leukocyte collection
- Before entering the trial, women must adopt a reliable method of contraception until 30 days after infusion.
- Understand this trial and have signed an informed consent
Exclusion Criteria:
- Patients with symptomatic brain metastasis
- With other uncontrolled malignant tumors.
- Hepatitis B or Hepatitis C activity period, HIV infected patients
- Any other uncontrolled disease that interferes with the trial
- Patients with severe heart and cerebrovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis and cerebral hemorrhage
- Untreated hypertension or hypertensive patients
- A person with a history of mental illness that is difficult to control
- Researchers do not consider it appropriate to participate in this trial
- Patients who have been using immunosuppressive agents for a long time after organ transplants, except for recent or current inhaled corticosteroids
- Subjects who have been pregnant or nursing, or who plan for pregnancy within 2 months of treatment or after the end of treatment
- An illness affects a person who signs a written consent or complies with a study procedure, or who is unwilling or unable to comply with the research requirements
Sites / Locations
- Qingzhu JiaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
HPV TCR-T
HPV TCR-T with anti-PD1
Arm Description
HPV E6-specific TCR-T cell
HPV E6-specific TCR-T cell with anti-PD1 auto-secreted element
Outcomes
Primary Outcome Measures
To Determine the Maximum Tolerated Dose
Verify the MTD of TCR-T cells for HPV16 E6 antigen for treatment. Nine patients will be enrolled in this project, using a dose-climbing approach, with every three patients as a group. The first group of patients returned to 5x106/kg TCR-T cells, the second group returned to 1x107/kg TCR-T cells, and the third group returned to 5x107/kg TCR-T cells
Secondary Outcome Measures
Full Information
NCT ID
NCT03578406
First Posted
May 28, 2018
Last Updated
April 29, 2019
Sponsor
Xinqiao Hospital of Chongqing
Collaborators
TCRCure Biopharma Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03578406
Brief Title
HPV-E6-Specific Anti-PD1 TCR-T Cells in the Treatment of HPV-Positive NHSCC or Cervical Cancer
Official Title
Two-Arm Open-Labeled Trial of HPV-E6-Specific TCR-T Cells With or Without Anti-PD1 Auto-secreted Element in the Treatment of HPV-Positive Head and Neck Carcinoma or Cervical Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
August 30, 2020 (Anticipated)
Study Completion Date
August 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Xinqiao Hospital of Chongqing
Collaborators
TCRCure Biopharma Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Human papillomavirus infections 16 (HPV16) is known to be a high-risk factor to induce cervical cancers. To date, HPV16-related cervical cancer is still a major concern in developing countries where vaccination is not prevalent. Concurrent therapies for cervical cancers have limited response rate and high chance of relapse. However, HPV16-induced cancers provided an ideal target for T cell-based immunotherapy due to the non-self origins. Engineered T cells bearing a TCR (TCR-T) that can specifically recognize the presented HPV antigen become a viable approach to treat this type of cancer. Though engineered T therapies have been well-recognized in hematological cancers, solid cancer treatment has been a major hurdle due to the immune-suppressive tumor microenvironment. One key mechanism of tumor-elicited suppression is the PDL1-PD1 interaction which induces T cell exhaustion. Therefore, TCR-T cells armed with a PD1 antagonist could further enhance the efficacy of TCR-T in solid cancers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer, Head and Neck Squamous Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HPV TCR-T
Arm Type
Experimental
Arm Description
HPV E6-specific TCR-T cell
Arm Title
HPV TCR-T with anti-PD1
Arm Type
Experimental
Arm Description
HPV E6-specific TCR-T cell with anti-PD1 auto-secreted element
Intervention Type
Drug
Intervention Name(s)
HPV E6-specific TCR-T cells
Intervention Description
Patients were infused with HPV E6-specific TCR-T cells
Primary Outcome Measure Information:
Title
To Determine the Maximum Tolerated Dose
Description
Verify the MTD of TCR-T cells for HPV16 E6 antigen for treatment. Nine patients will be enrolled in this project, using a dose-climbing approach, with every three patients as a group. The first group of patients returned to 5x106/kg TCR-T cells, the second group returned to 1x107/kg TCR-T cells, and the third group returned to 5x107/kg TCR-T cells
Time Frame
8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Expected to live longer than 12 weeks
PS 0-2
Pathology confirmed as HPV16 positive malignant tumor, either metastatic or recurrent disease
Creatinine <2.5mg/dl
ALT/AST is lower than three times ULN.
No contraindications of leukocyte collection
Before entering the trial, women must adopt a reliable method of contraception until 30 days after infusion.
Understand this trial and have signed an informed consent
Exclusion Criteria:
Patients with symptomatic brain metastasis
With other uncontrolled malignant tumors.
Hepatitis B or Hepatitis C activity period, HIV infected patients
Any other uncontrolled disease that interferes with the trial
Patients with severe heart and cerebrovascular diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis and cerebral hemorrhage
Untreated hypertension or hypertensive patients
A person with a history of mental illness that is difficult to control
Researchers do not consider it appropriate to participate in this trial
Patients who have been using immunosuppressive agents for a long time after organ transplants, except for recent or current inhaled corticosteroids
Subjects who have been pregnant or nursing, or who plan for pregnancy within 2 months of treatment or after the end of treatment
An illness affects a person who signs a written consent or complies with a study procedure, or who is unwilling or unable to comply with the research requirements
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Qingzhu Jia
Phone
+8615223334184
Ext
+8615223334184
Email
jiaqingzhu0801@outlook.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bo Zhu
Organizational Affiliation
Oncology of Department, Xinqiao Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Qingzhu Jia
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400037
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qingzhu Jia
Phone
+8615223334184
Ext
+8615223334184
Email
jiaqingzhu0801@outlook.com
12. IPD Sharing Statement
Learn more about this trial
HPV-E6-Specific Anti-PD1 TCR-T Cells in the Treatment of HPV-Positive NHSCC or Cervical Cancer
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