A phase 1 clinical trial of intraperitoneal administration of iCAR-ILC/N101 for ovarian clear cell carcinoma

JRCT ID: jRCT2033200431

Registered date:18/03/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Patients with GPC3-expressing advanced ovarian clear cell carcinoma with peritoneal dissemination
• Date of first enrollment: 10/05/2021
• Target sample size: 18
• Study type: Interventional
• Intervention(s): As iCAR-ILC-N101, 1 x 10^6 cells/kg is administered once a week, up to 4 times percutaneously repeatedly. Depend on the DLT, the minimum dose is 0.5 x 10^6 cells/kg/once, 4 times in 22 days, and the maximum dose is 3 x 10^6 cells/kg/once, 8 times in 50 days.

Outcome(s)

• Primary Outcome: Adverse events including the dose limiting toxicity on iCAR-ILC-N101
• Secondary Outcome: Efficacy of iCAR-ILC-N101(Objective response rate, Disease control rate, Progression free survival, Overall survival)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Female

Include criteria

1. 1st time registration
1) Histologically diagnosed advanced or metastatic ovarian clear cell carcinoma with radiographically confirmed peritoneal metastases irrespective of metastases in other organs.
2) Patients who have progressed after receiving standard treatments for ovarian cancer.
3) At least one measurable lesion as defined by RECIST ver.1.1, and/or non-target lesion such as the malignant ascites retention.
4) Tumor must be glypican-3-positive by immunohistochemistry.
5) Age at registration is of 20 years or older.
6) ECOG Performance status, 0-2.
7) HLA typing, HLA-A24 or HLA-B52.
8) Adequate organ function by laboratory parameters within 7 days prior to the enrollment.
9) A non-pregnant female. Female of childbearing potential who are negative in a pregnancy test within 7 days before enrollment. Patients should agree to use an adequate method of contraception in this study and in the future.
10) The patient survival is expected to be longer than 3 months after registration.
11) Patients who provided written informed consent to be subjects in this study.
2. 2nd time registration
1)-11) Patients met inclusion Criteria of 1st time registration.
12) Patients who was able to produce iCAR-ILC-N101 at least 0.5 x 10^6 cells/kg/dose based on weight at the time of apheresis. Expansion cohort ; Patients for whom at least 4 doses of 3.0 x 10^6 cells/kg/once is able to be produced in the first production and more than 8 doses of cells can be expected to be produced in the second production

Exclude criteria

1. 1st time registration
1) Synchronous or metachronous (within 2 years) malignancies.
2) Patients who has or is suspected to have bacterial infection or virus infection.
3) Patients who require platelet or red blood cell transfusion within 14 days prior to the apheresis.
4) Severe cardiovascular disease.
5) Has concurrent interstitial lung disease/pneumonitis, or a history of (noninfectious) interstitial lung disease/pneumonitis that required treatment with steroids.
6) History of hypersensitivity reactions to biological ingredients.
7) Females who are pregnant or breastfeeding.
8) History of the therapy derived from induced pluripotent stem cells.
9) Has pericardial effusion, pleural effusion requiring any therapies.
10) Has a history of cerebral infarction, cerebral hemorrhage, or transient cerebral ischemia within 180 days prior to enrollment.
11) Has a history of deep vein thrombosis or pulmonary embolism.
12) Is receiving systemic corticosteroids therapy or systemic immunosuppressive therapy.
13) Has received a live vaccine within 28 days prior to enrollment.
14) Has active brain metastasis or a tumor causing spinal cord compression.
15) Patients who is considered to interfere with evaluation of the study therapy or safety or interpretation of study results.
2. 2nd time registration
1)-15) Patients met exclusion Criteria of 1st time registration.
16) Has received prior antitumor therapy (e.g., chemotherapy, molecular-targeted therapy, therapeutic antibody, endocrine therapy, immunotherapy, and investigational therapy) or other investigational drug after 1st time registration.
17) Has received radiotherapy after 1st time registration.
18) Has received surgery under general anesthesia within 28 days prior to 2nd time registration.
19) Is not eligible to enroll in the clinical trial based on the judgment by the Principal Investigator or Sub-investigator.

Related Information

• Primary Sponsor: Harano Kenichi
• Source(s) of Monetary Support: AMED