Clinical trial NCT03814447: The Fourth Generation CART-cell Therapy for Refractory-Relapsed Ovarian Cancer
Official title: The Clinical Research of Fourth Generation CART-cell Therapy in Refractory-Relapsed Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Ovarian Cancer
Keywords: MESO
CAR-T
Ovarian cancer
Refractory-Relapsed
Lead sponsor: Shanghai 6th People's Hospital
Sponsor class: OTHER
Collaborators: name: Hrain Biotechnology Co., Ltd.
First posted: 2019-01-24
Enrollment: 10
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to study the safety and feasibility of anti- Mesothelin Chimeric Antigen Receptor T-Cell (MESO CAR-T cells) therapy for Refractory-Relapsed Ovarian Cancer

Detailed description: Primary Objectives:

1. To determine the safety and feasibility of anti- MESO CAR-T cells therapy for Refractory-Relapsed Ovarian Cancer

Secondary Objectives:

1. To access the efficacy of anti- MESO CAR-T cells in patients with ovarian cancer.
2. To determine in vivo dynamics and persistency of anti- MESO CAR-T cells
3. To assess the quality of life in patients with ovarian cancer after treatment with anti- MESO CAR-T cells.

Eligibility criteria: Inclusion Criteria:

1. Histopathologically confirmed ovarian cancer;
2. 18-75 Years Old, female;
3. Expected survival \> 12 weeks;
4. Eastern Cooperative Oncology Group (ECOG) score 0-2;
5. Patients who have previously been treated with second- line or above standard treatment are failed (progress in treatment or recurrence within 6 months after discontinuation of treatment);
6. According to the Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST) , there should be at least one measurable tumor foci；
7. Positive expression of Mesothelin in tumor tissue；
8. Creatinine ≤ 1.5×ULN or creatinine clearance ≥ 60ml / min;
9. alanine aminotransferase and aspartate aminotransferase ≤ 2.5×ULN , such as with liver metastasis, ≤ 5×ULN;
10. Total bilirubin ≤ 2×ULN;
11. Hemoglobin≥90g/L(No blood transfusion within 14 days);
12. Absolute value of neutrophils ≥1.5×10\^9/L;
13. Absolute counting of lymphocytes \>0.7×10\^9/L;
14. Counting of Platelet≥80×10\^9/L；
15. The venous access required for collection can be established without contraindications for leukocyte collection;
16. Able to understand and sign the Informed Consent Document.

Exclusion Criteria:

1. Accompanied by other uncontrolled malignant tumors;
2. Active hepatitis B, hepatitis C, syphilis, HIV infection;
3. Insufficient function of important organs (heart, lung);
4. Any other uncontrolled active disease that impedes participation in the trial;
5. Any affairs could affect the safety of the subjects or purpose this trial;
6. Pregnant or lactating women, or patients who plan to be pregnancy during or after treatment;
7. There are active or uncontrollable infections (except simple urinary tract infections or upper respiratory tract infections) that require systemic therapy within 14 days or 14 days prior to enrollment；
8. The investigator believes that it is not appropriate to participate in the trial;
9. Received CAR-T treatment or other gene therapies before enrollment; Subjects suffering disease affect the understanding of informed consent or unable to comply with study; Unwilling or unable to comply with study requirements.

Primary outcomes:
measure: Adverse events (AEs) and Serious adverse event (SAEs)
timeFrame: 1 year post infusion
Secondary outcomes:
measure: Cmax
timeFrame: 30 days post infusion
measure: Tmax
timeFrame: 30 days post infusion
measure: AUC(0-30d)
timeFrame: 30 days post infusion
measure: Duration of Mesothelin-positive T cells in circulation
timeFrame: 90 days post infusion
measure: ORR
timeFrame: 3 months post infusion
measure: PFS
timeFrame: 1 year post infusion
measure: EORTC Quality-of-Life Questionnaire Core 15 Palliative Care (QLQ-C15-PAL) of patients after administration
timeFrame: 1 year post infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai 6th People's Hospital
state: Shanghai
Study officials:
affiliation: Shanghai 6th People's Hospital
name: Hui Zhao, doctor
role: PRINCIPAL_INVESTIGATOR
References: