Clinical trial NCT03356795: 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
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Cervical Cancer
Keywords: Cervical cancer
CAR-T
GD2
PSMA
Muc1
Mesothelin
HPV
solid tumor
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2017-11-29
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety of CART cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
timeFrame: 3 months
Secondary outcomes:
measure: Persistence and proliferation of CART cells in patients
timeFrame: 3 months
measure: Anti-tumor effects
timeFrame: 1 year
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, PhD
role: PRINCIPAL_INVESTIGATOR
References: