Intervention of CAR-T Against Cervical Cancer

• ClinicalTrials.gov Identifier: NCT03356795
• Recruitment Status: Unknown
• First Posted: November 29, 2017
• Last Update Posted: September 19, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: November 24, 2017
• First Posted Date: November 29, 2017
• Last Update Posted Date: September 19, 2019
• Actual Study Start Date: November 15, 2017
• Actual Primary Completion Date: January 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 24, 2017)

Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [ Time Frame: 3 months ]

Physiological parameter (measuring cytokine response)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 24, 2017)

• Persistence and proliferation of CART cells in patients [ Time Frame: 3 months ]
  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 [ Time Frame: 1 year ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cervical Cancer

Intervention

Biological: Cervical cancer-specific CAR-T cells

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

Study Arms

Experimental: Cervical cancer-specific CAR-T cells

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.

Intervention: Biological: Cervical cancer-specific CAR-T cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 24, 2017): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2020
• Actual Primary Completion Date: January 31, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients with stage III, IV or relapsed cervical cancer confirmed by histology and biopsy.
2. Age: ≥ 18 years and ≤ 70 years.
3. 4 weeks at least since last chemotherapy or radiotherapy and 2 weeks at least since last systemic steroid hormone and other immunosuppressive therapy.
4. Side Effects of Chemotherapy have subsided.
5. GD2, PSMA, Muc1, Mesothelin or other markers is expressed high (above 2+) in malignancy tissues by immuno-histochemical or flow cytometry.
6. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
7. Expected survival ≥ 12 weeks.

8. Initial hematopoietic reconstitution with

   • neutrophils (ANC) ≥ 1×10^6/L;
   • platelet (PLT) ≥ 1×10^8/L.

9. 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.
10. Oxygen saturation ≥ 90%.
11. Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

1. Airway obstruction caused by tumor.
2. History of epilepsy or other central nervous system diseases.
3. Patients who require systemic corticosteroid or other immunosuppressive therapy.
4. History of prolonged or serious heart disease during QT.
5. history of serious cyclophosphamide toxicity.
6. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study.

7. Inadequate liver and renal function with

   • serum creatinine > 1.5 mg/dl;
   • serum (total) bilirubin > 2.0 mg/dl;
   • AST & ALT > 3 x ULN.
8. Pregnant or lactating females.
9. Serious active infection during screening.
10. Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.
11. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03356795
• Other Study ID Numbers: GIMI-IRB-17017
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Lung-Ji Chang, PhD; Shenzhen Geno-Immune Medical Institute

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: September 2019