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Intervention of CAR-T Against Cervical Cancer

Primary Purpose

Cervical Cancer

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Cervical cancer-specific CAR-T cells

About this trial

This is an interventional treatment trial for Cervical Cancer focused on measuring Cervical cancer, CAR-T, GD2, PSMA, Muc1, Mesothelin, HPV, solid tumor

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Patients with stage III, IV or relapsed cervical cancer confirmed by histology and biopsy.
Age: ≥ 18 years and ≤ 70 years.
4 weeks at least since last chemotherapy or radiotherapy and 2 weeks at least since last systemic steroid hormone and other immunosuppressive therapy.
Side Effects of Chemotherapy have subsided.
GD2, PSMA, Muc1, Mesothelin or other markers is expressed high (above 2+) in malignancy tissues by immuno-histochemical or flow cytometry.
Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
Expected survival ≥ 12 weeks.
Initial hematopoietic reconstitution with
- neutrophils (ANC) ≥ 1×10^6/L;
- platelet (PLT) ≥ 1×10^8/L.
Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with
- serum creatinine ≤ 2×ULN;
- serum bilirubin ≤ 3×ULN;
- AST/ALT ≤ 2.5×ULN.
Oxygen saturation ≥ 90%.
Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

Airway obstruction caused by tumor.
History of epilepsy or other central nervous system diseases.
Patients who require systemic corticosteroid or other immunosuppressive therapy.
History of prolonged or serious heart disease during QT.
history of serious cyclophosphamide toxicity.
Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study.
Inadequate liver and renal function with
- serum creatinine > 1.5 mg/dl;
- serum (total) bilirubin > 2.0 mg/dl;
- AST & ALT > 3 x ULN.
Pregnant or lactating females.
Serious active infection during screening.
Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Sites / Locations

Shenzhen Geno-immune Medical InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cervical cancer-specific CAR-T cells

Arm Description

Peripheral blood mononuclear cells (PBMCs) of patients who have GD2, PSMA, Muc1 or Mesothelin positive cervical cancer will be obtained through apheresis, and T cells will be activated and modified to cervical cancer-specific CAR-T cells.

Outcomes

Primary Outcome Measures

Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events

Physiological parameter (measuring cytokine response)

Secondary Outcome Measures

Persistence and proliferation of CART cells in patients

The expansion and functional persistence of CART cells in the peripheral blood of patients will be measured by qPCR on Day 7, 14, 21, 28, 60 and 90 after infusion.

Anti-tumor effects

Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

Full Information

NCT ID

NCT03356795

First Posted

November 24, 2017

Last Updated

September 18, 2019

Sponsor

Shenzhen Geno-Immune Medical Institute

1. Study Identification

Unique Protocol Identification Number

NCT03356795

Brief Title

Intervention of CAR-T Against Cervical Cancer

Official Title

Multicenter Trial of Chimeric Antigen Receptor-Modified T Cells (CAR-T Cells) in the Treatment of Cervical Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Unknown status

Study Start Date

November 15, 2017 (Actual)

Primary Completion Date

January 31, 2019 (Actual)

Study Completion Date

December 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shenzhen Geno-Immune Medical Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of CAR T cells immunotherapy in patients who have GD2, PSMA, Muc1, Mesothelin or other markers positive cervical cancer. Another goal of the study is to learn more about the persistence and function of CAR T cells in the body.

Detailed Description

Cervical cancer is a cancer arising from the cervix. Human papillomavirus (HPV) infection causes more than 90% of cases. Other risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners, but these are less important. Worldwide, cervical cancer is both the fourth-most common cause of cancer and the fourth-most common cause of death from cancer in women. The treatment of cervical cancer consists of surgical intervention, radiation, chemotherapy and immunotherapy. In this study, the participant's T-cells will be collected and modified. Then the modified T cells, called chimeric antigen receptor modified-T cells (CAR T) which can recognize specific molecules that are expressed on the surface of cervical cancer cells, are given back to the participant by intravenous infusion. The purpose of this clinical trial is to assess the feasibility, safety and efficacy of CAR T cells immunotherapy in patients who have GD2, PSMA, Muc1, Mesothelin or other markers positive cervical cancer. Another goal of the study is to learn more about the persistence and function of CAR T cells in the body.

6. Conditions and Keywords

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

Cervical Cancer

Keywords

Cervical cancer, CAR-T, GD2, PSMA, Muc1, Mesothelin, HPV, solid tumor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cervical cancer-specific CAR-T cells

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Cervical cancer-specific CAR-T cells

Intervention Description

1 infusion, for 1x10^6~1x10^7 cells/kg via IV

Primary Outcome Measure Information:

Title

Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events

Description

Physiological parameter (measuring cytokine response)

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Persistence and proliferation of CART cells in patients

Description

The expansion and functional persistence of CART cells in the peripheral blood of patients will be measured by qPCR on Day 7, 14, 21, 28, 60 and 90 after infusion.

Time Frame

3 months

Title

Anti-tumor effects

Description

Time Frame

1 year

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with stage III, IV or relapsed cervical cancer confirmed by histology and biopsy. Age: ≥ 18 years and ≤ 70 years. 4 weeks at least since last chemotherapy or radiotherapy and 2 weeks at least since last systemic steroid hormone and other immunosuppressive therapy. Side Effects of Chemotherapy have subsided. GD2, PSMA, Muc1, Mesothelin or other markers is expressed high (above 2+) in malignancy tissues by immuno-histochemical or flow cytometry. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1. Expected survival ≥ 12 weeks. Initial hematopoietic reconstitution with neutrophils (ANC) ≥ 1×10^6/L; platelet (PLT) ≥ 1×10^8/L. Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with serum creatinine ≤ 2×ULN; serum bilirubin ≤ 3×ULN; AST/ALT ≤ 2.5×ULN. Oxygen saturation ≥ 90%. Written, informed consent obtained prior to any study-specific procedures. Exclusion Criteria: Airway obstruction caused by tumor. History of epilepsy or other central nervous system diseases. Patients who require systemic corticosteroid or other immunosuppressive therapy. History of prolonged or serious heart disease during QT. history of serious cyclophosphamide toxicity. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study. Inadequate liver and renal function with serum creatinine > 1.5 mg/dl; serum (total) bilirubin > 2.0 mg/dl; AST & ALT > 3 x ULN. Pregnant or lactating females. Serious active infection during screening. Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Lung-Ji Chang, PhD

Phone

86-075586725195

c@szgimi.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lung-Ji Chang, PhD

Organizational Affiliation

Shenzhen Geno-Immune Medical Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shenzhen Geno-immune Medical Institute

City

Shenzhen

State/Province

Guangdong

ZIP/Postal Code

518000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lung-Ji Chang, PhD

Phone

86-075586725195

c@szgimi.org

12. IPD Sharing Statement

Plan to Share IPD

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Intervention of CAR-T Against Cervical Cancer

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