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U87 CART in Treatment of Advanced Pancreatic Cancer

Primary Purpose

Pancreatic Cancer

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
U87 CAR-T
Sponsored by
Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Voluntary informed consent is given; Age 18 to 75; Patients with pathologically confirmed advanced pancreatic cancer who have failed first-line therapy; or patients who are intolerant to first-line standard therapy and voluntarily give up standard therapy; Immunohistochemical (IHC) staining of tumor tissue samples from patients was positive for U87 specific antigen (≥ 2 +, and the expression rate was ≥ 20%); Expected survival ≥12 weeks; Measurable tumor lesions according to RECIST 1.1; ECOG performance score 0-1; Sufficient venous access for mononuclear cell collection; HBc Ab positive, HBsAg negative can be included in the group when the PCR detection of HBV DNA is negative; Patients should maintain adequate organ function; Dyspnea (CTCAE v5.0) ≤ Grade 1; Blood oxygen saturation>91% without oxygen inhalation; Pregnancy test was negative in women of childbearing age; Both male and female subjects should agree to use effective contraceptives during the treatment period and within the following year; Exclusion Criteria: Pregnant or lactating women; Uncontrolled active infections; Active Syphilis, HIV, hepatitis B or hepatitis C infection; Congenital immunodeficiency; Have serious allergic reaction to any drug to be used in this study; Other incurable malignant tumors in the past three years; History or presence of clinically relevant CNS pathology such as epilepsy, Cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS-related autoimmune disease; Have undergone cardiac angioplasty or stent implantation within 12 months, or have a history of myocardial infarction, unstable angina or other clinically significant heart diseases; Subjects requiring anticoagulation or long-term antiplatelet therapy; Subjects who have undergone major surgery or significant trauma within four weeks before enrolled in the study. Other situations that the investigator thinks are not suitable for participating in this study.

Sites / Locations

  • China Shanghai 10th People's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

U87 CAR-T cells

Arm Description

The Patients are enrolled into 2 dose level cohorts in sequence

Outcomes

Primary Outcome Measures

Incidence of Adverse events after U87 CAR-T cells infusion [Safety and Tolerability]
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0) Dose-limiting toxicity after U87 CAR-T cells infusion.

Secondary Outcome Measures

Disease control rate (DCR) of U87 CAR-T cells treatment in advanced pancreatic cancer. [Effectiveness]
Disease control rate: including CR, PR and SD(Assessed based on RECIST 1.1 criteria)
Objective response rate (ORR) of U87 CAR-T cells treatment in advanced pancreatic cancer. [Effectiveness]
Objective response rate includes:CR、PR(Assessed based on RECIST1.1 criteria)
Duration of Response (DOR) of U87 CAR-T cells treatment in advanced pancreatic cancer [Effectiveness]
DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause
Progress-free survival(PFS) of U87 CAR-T cells treatment in advanced pancreatic cancer [Effectiveness]
PFS will be assessed from the first U87 CAR-T cells infusion to death from any cause or the first assessment of progression(Assessed based on RECIST1.1 ) criteria)
Overall survival(OS) of U87 CAR-T cells treatment in advanced pancreatic cancer [Effectiveness]
OS will be assessed from the first U87 CAR-T cells infusion to death from any cause (Assessed based on RECIST 1.1 criteria)
Pharmacokinetics of U87 CAR-T cells
Peak value of eripheral blood (Cmax)
Pharmacokinetics of U87 CAR-T cells
Area under the eripheral blood concentration versus time curve (AUC)
Pharmacokinetics of U87 CAR-T cells
Time of peak value
Pharmacodynamics of U87 CAR-T cells
Concentration levels of CAR-T-related serum cytokines such as IL-6, IFN γ, IL-2, TNFα, ferritin and CRP at each time point

Full Information

First Posted
October 3, 2022
Last Updated
October 29, 2022
Sponsor
Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
Collaborators
Shanghai 10th People's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05605197
Brief Title
U87 CART in Treatment of Advanced Pancreatic Cancer
Official Title
Clinical Study to Evaluate the Safety and Efficacy of U87 CART in Treatment of Advanced Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 19, 2022 (Actual)
Primary Completion Date
October 8, 2023 (Anticipated)
Study Completion Date
October 8, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
Collaborators
Shanghai 10th People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
This is a single center, open-label, phase 1 study to evaluate the safety and efficacy of U87 CART in treating advanced Pancreatic Cancer.
Detailed Description
Following consent, patients must have tumor tissue evaluated by IHC assay. Patients meeting all eligibility criteria will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (U87). Following manufacture of the drug product, subjects will receive preconditioning prior to U87 infusion. All subjects will be asked to continue to undergo long-term gene safety follow-up.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
U87 CAR-T cells
Arm Type
Experimental
Arm Description
The Patients are enrolled into 2 dose level cohorts in sequence
Intervention Type
Drug
Intervention Name(s)
U87 CAR-T
Intervention Description
Subjects will be pretreated with cyclophosphamide 250~500 mg/m2( body surface area) for 3 days prior to Intratumoral injection of U87, followed by intraartery of U87 14 days later with intravenous IL-2. This study will explore two dose of dose 1 (DL-1): 1×106 (±20%) to dose 2 (DL-2): 1×107 (±20%),each group was enrolled in 3~6 patients.
Primary Outcome Measure Information:
Title
Incidence of Adverse events after U87 CAR-T cells infusion [Safety and Tolerability]
Description
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0) Dose-limiting toxicity after U87 CAR-T cells infusion.
Time Frame
28 days post administration of CAR-T-cells
Secondary Outcome Measure Information:
Title
Disease control rate (DCR) of U87 CAR-T cells treatment in advanced pancreatic cancer. [Effectiveness]
Description
Disease control rate: including CR, PR and SD(Assessed based on RECIST 1.1 criteria)
Time Frame
2 years post CAR T cell infusion
Title
Objective response rate (ORR) of U87 CAR-T cells treatment in advanced pancreatic cancer. [Effectiveness]
Description
Objective response rate includes:CR、PR(Assessed based on RECIST1.1 criteria)
Time Frame
2 years post CAR T cell infusion
Title
Duration of Response (DOR) of U87 CAR-T cells treatment in advanced pancreatic cancer [Effectiveness]
Description
DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause
Time Frame
2 years post CAR T cell infusion
Title
Progress-free survival(PFS) of U87 CAR-T cells treatment in advanced pancreatic cancer [Effectiveness]
Description
PFS will be assessed from the first U87 CAR-T cells infusion to death from any cause or the first assessment of progression(Assessed based on RECIST1.1 ) criteria)
Time Frame
2 years post CAR T cell infusion
Title
Overall survival(OS) of U87 CAR-T cells treatment in advanced pancreatic cancer [Effectiveness]
Description
OS will be assessed from the first U87 CAR-T cells infusion to death from any cause (Assessed based on RECIST 1.1 criteria)
Time Frame
2 years post CAR T cell infusion
Title
Pharmacokinetics of U87 CAR-T cells
Description
Peak value of eripheral blood (Cmax)
Time Frame
2 years post CAR T cell infusion
Title
Pharmacokinetics of U87 CAR-T cells
Description
Area under the eripheral blood concentration versus time curve (AUC)
Time Frame
2 years post CAR T cell infusion
Title
Pharmacokinetics of U87 CAR-T cells
Description
Time of peak value
Time Frame
2 years post CAR T cell infusion
Title
Pharmacodynamics of U87 CAR-T cells
Description
Concentration levels of CAR-T-related serum cytokines such as IL-6, IFN γ, IL-2, TNFα, ferritin and CRP at each time point
Time Frame
2 years post CAR T cell infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Voluntary informed consent is given; Age 18 to 75; Patients with pathologically confirmed advanced pancreatic cancer who have failed first-line therapy; or patients who are intolerant to first-line standard therapy and voluntarily give up standard therapy; Immunohistochemical (IHC) staining of tumor tissue samples from patients was positive for U87 specific antigen (≥ 2 +, and the expression rate was ≥ 20%); Expected survival ≥12 weeks; Measurable tumor lesions according to RECIST 1.1; ECOG performance score 0-1; Sufficient venous access for mononuclear cell collection; HBc Ab positive, HBsAg negative can be included in the group when the PCR detection of HBV DNA is negative; Patients should maintain adequate organ function; Dyspnea (CTCAE v5.0) ≤ Grade 1; Blood oxygen saturation>91% without oxygen inhalation; Pregnancy test was negative in women of childbearing age; Both male and female subjects should agree to use effective contraceptives during the treatment period and within the following year; Exclusion Criteria: Pregnant or lactating women; Uncontrolled active infections; Active Syphilis, HIV, hepatitis B or hepatitis C infection; Congenital immunodeficiency; Have serious allergic reaction to any drug to be used in this study; Other incurable malignant tumors in the past three years; History or presence of clinically relevant CNS pathology such as epilepsy, Cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS-related autoimmune disease; Have undergone cardiac angioplasty or stent implantation within 12 months, or have a history of myocardial infarction, unstable angina or other clinically significant heart diseases; Subjects requiring anticoagulation or long-term antiplatelet therapy; Subjects who have undergone major surgery or significant trauma within four weeks before enrolled in the study. Other situations that the investigator thinks are not suitable for participating in this study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maoquan Li, doctor
Phone
021-66300114*3506
Email
cjr.limaoquan@vip.163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Shilong Han, doctor
Phone
021-66303247
Facility Information:
Facility Name
China Shanghai 10th People's Hospital
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li mao quan, doctor
Phone
021-66300114
Ext
3506
Email
cjr.limaoquan@vip.163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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U87 CART in Treatment of Advanced Pancreatic Cancer

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