Back to resultsCLDN6-CAR-NK Cell Therapy for Advanced Solid Tumors
Primary Purpose
Stage IV Ovarian Cancer, Testis Cancer, Refractory, Endometrial Cancer Recurrent
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Claudin6 targeting CAR-NK cells
Sponsored by
About this trial
This is an interventional treatment trial for Stage IV Ovarian Cancer focused on measuring Solid tumor, Claudin6, CAR NK
Eligibility Criteria
Inclusion Criteria:
- patients with advanced ovarian cancer or other cancers with expression of claudin6.
- Life expectancy >12 weeks
- Adequate heart,lung,liver,kidney function
- Available autologous transduced NK cells with greater than or equal to 20% expression of claudin6-CAR determined by flow-cytometry and killing of claudin6-positive targets greater than or equal to 20% in cytotoxicity assay
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -
Exclusion Criteria:
- Had accepted gene therapy before;
- Tumor size more than 25cm;
- Severe virus infection such as HBV,HCV,HIV,et al
- Known HIV positivity
- History of liver/renal transplantation
- Active infectious disease related to bacteria, virus,fungi,et al
- Other severe diseases that the investigators consider not appropriate;
- Pregnant or lactating women
- Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
- Other conditions that the investigators consider not appropriate. -
Sites / Locations
- The Second Affiliated Hospital of Guangzhou Medical UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CAR-NK cell therapy group
Arm Description
Appropriate patients who could benefit from the claudin6 targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell therapy group.
Outcomes
Primary Outcome Measures
Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0
The type, frequency, severity, and duration of adverse events as a result of Claudin6- CAR-NK cells infusion will be summarized.
Secondary Outcome Measures
Objective Response Rate (ORR)
Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response, prior to progression or further anti-cancer therapy.
Disease control rate (DCR)
Disease control rate (DCR) defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, SD assessed at least 6 weeks after the first dose) is observed as best overall response.
Duration of response (DOR)
Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (Progressive disease (PD) per RECIST 1.1/recurrence) or death from any cause, whichever occurs first.
Full Information
NCT ID
NCT05410717
First Posted
June 5, 2022
Last Updated
June 5, 2022
Sponsor
Second Affiliated Hospital of Guangzhou Medical University
1. Study Identification
Unique Protocol Identification Number
NCT05410717
Brief Title
CLDN6-CAR-NK Cell Therapy for Advanced Solid Tumors
Official Title
Phase I/IIa Trial to Evaluate Safety and Preliminary Efficacy of CLDN6-CAR-NK in Patients With CLDN6-positive Advanced Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2022 (Actual)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
May 31, 2034 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Second Affiliated Hospital of Guangzhou Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study is a single-arm, open, exploratory clinical study to evaluate the safety and preliminary efficacy of Claudin6 targeting CAR-NK cells in patients with Claudin6-positive advanced solid tumors (ovarian cancer and others)
Detailed Description
Choose appropriate advanced cancer patients with Claudin6 expression, with written consent for the study;
Perform PBMCs apheresis from the patient and isolate NK cells, transfect the NK cells with Claudin6 targeting CAR, amplify the number of transfected NK cells as needed, test the quality and killing activity of the Claudin6-CAR-NK cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed;
To enhance the killing capability, some CAR-NK cells are genetically engineered to express and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Lag3;
Evaluate the clinical results as needed.
Will also perform the similar clinical trial on different cancer types with Claudin6 expression.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IV Ovarian Cancer, Testis Cancer, Refractory, Endometrial Cancer Recurrent, CAR NK
Keywords
Solid tumor, Claudin6, CAR NK
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CAR-NK cell therapy group
Arm Type
Experimental
Arm Description
Appropriate patients who could benefit from the claudin6 targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell therapy group.
Intervention Type
Biological
Intervention Name(s)
Claudin6 targeting CAR-NK cells
Intervention Description
Engineering Claudin6 targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Lag3 secreting vector into NK cells, which are isolated from patients with advanced ovarian cancer or other cancers with expression of Claudin6, and then transfusing them back the patients.
Primary Outcome Measure Information:
Title
Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0
Description
The type, frequency, severity, and duration of adverse events as a result of Claudin6- CAR-NK cells infusion will be summarized.
Time Frame
After CAR-NK cells infusion, up to 52 weeks.
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response, prior to progression or further anti-cancer therapy.
Time Frame
After CAR-NK cells infusion, up to 52 weeks.
Title
Disease control rate (DCR)
Description
Disease control rate (DCR) defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, SD assessed at least 6 weeks after the first dose) is observed as best overall response.
Time Frame
up to 52 weeks.
Title
Duration of response (DOR)
Description
Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (Progressive disease (PD) per RECIST 1.1/recurrence) or death from any cause, whichever occurs first.
Time Frame
up to 36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
patients with advanced ovarian cancer or other cancers with expression of claudin6.
Life expectancy >12 weeks
Adequate heart,lung,liver,kidney function
Available autologous transduced NK cells with greater than or equal to 20% expression of claudin6-CAR determined by flow-cytometry and killing of claudin6-positive targets greater than or equal to 20% in cytotoxicity assay
Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -
Exclusion Criteria:
Had accepted gene therapy before;
Tumor size more than 25cm;
Severe virus infection such as HBV,HCV,HIV,et al
Known HIV positivity
History of liver/renal transplantation
Active infectious disease related to bacteria, virus,fungi,et al
Other severe diseases that the investigators consider not appropriate;
Pregnant or lactating women
Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
Other conditions that the investigators consider not appropriate. -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhenfeng Zhang, MD, PHD
Phone
+862039195966
Email
zhangzhf@gzhmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Bingjia He, MD
Phone
+862039195965
Email
464677938@qq.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PHD
Organizational Affiliation
Second Affiliated Hospital of Guangzhou Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Second Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhenfeng Zhang, MD, PHD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
CLDN6-CAR-NK Cell Therapy for Advanced Solid Tumors
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