Intervention of CAR-T Against Cervical Cancer

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

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 Overview

• Status: Unknown
• Conditions: Cervical Cancer
• Intervention / Treatment: Biological: Cervical cancer-specific CAR-T cells

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
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-Immune Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: Cervical cancer-specific CAR-T cells; 1 infusion, for 1x10^6~1x10^7 cells/kg via IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events	Physiological parameter (measuring cytokine response)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year
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.	3 months

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Actual): January 31, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: November 24, 2017
• First Submitted That Met QC Criteria: November 24, 2017
• First Posted (Actual): November 29, 2017

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: CAR-T; solid tumor; PSMA; GD2; HPV; Cervical cancer; Mesothelin; Muc1
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: GIMI-IRB-17017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No