Clinical trial NCT06478459: Endoscopic Ultrasound (EUS) Intratumoral Injection of CAR-NK Cells in the Treatment of Advanced Pancreatic Cancer
Official title: A Single-center, Single-arm, Open-label, Dose-escalation Clinical Study to Evaluate the Safety and Anti-tumor Efficacy of Intratumoral NKG2D CAR-NK Cell Injection Guided by EUS in the Treatment of Locally Advanced Pancreatic Cancer.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Pancreatic Cancer Non-resectable
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2024-06-27
Enrollment: 20
Sex: ALL
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: This is a single-center, single-arm, open-label, dose-escalation clinical study to evaluate the safety and anti-tumor efficacy of intratumoral NKG2D CAR-NK cell injection guided by endoscopic ultrasound in the treatment of locally advanced pancreatic cancer.


Eligibility criteria: Inclusion Criteria:

1. 18\~75 years old (including boundary value), both male and female.
2. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma or IPMN carcinogenesis.
3. Recurrent or unresectable locally advanced pancreatic cancer. Patients with technically resectable tumors but are considered as unable to undergo surgical treatment due to medical comorbidities or the patient\&#39;s refusal of surgery are also eligible for enrollment.
4. ECOG PS score of 0-1.
5. At least 3 months of life expectancy at screening, as judged by the investigator.
6. Subject has adequate organ and bone marrow function. Laboratory screening results should be within the stable range described below, and there should be no ongoing supportive care (\&#34;jaundice relieve\&#34; therapy such as PTCD, ENBD, or bile duct stenting is allowed when pancreatic cancer invades the common bile duct). a) Blood biochemistry: serum creatinine ≤ 1.5×ULN, serum total bilirubin ≤ 2.0×ULN, and serum liver aminotransferase ≤ 3 ×ULN b) Blood tests: neutrophil count ≥ 1.5×109/L, platelet count ≥ 60×109/L, hemoglobin ≥ 8.0g/dL, lymphocyte count ≥ 0.4×109/L;
7. Childbearing status: not pregnant and, if of childbearing potential, willing to use effective contraception from the time of signing the informed consent form until 6 months after the last cell infusion (women of childbearing potential include premenopausal women and women within 2 years of postmenopausal time).
8. Subjects must sign a written informed consent form.
9. Subjects must be voluntary and able to comply with the scheduled treatment regimen, laboratory tests, follow-up, and other study requirements.

Exclusion Criteria:

1. Pregnant and lactating females.
2. Received any anti-tumor therapy (including but not limited to radiotherapy, chemotherapy, or immunotherapy) for pancreatic cancer within 28 days prior to enrollment.
3. In the opinion of the investigator, the EUS technique poses undue risks to the subject, including but not limited to: - Previous EUS-FNA was technically deemed too difficult to perform; - Imaging showing multiple collateral vessels around or near the target tumor within the pancreas; - Presence of varicose veins near the target tumor. - If any of the above risk profiles become apparent after subject screening and/or enrollment, consideration should be given to withdrawal from the study prior to treatment.
4. History of malignancy within 5 years, with the exception of basal cell carcinoma of the skin and carcinoma in situ of the cervix.
5. Any other health condition by the judgment of the investigator would preclude participation in the study.

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: within 28 days after NKG2D CAR-NK treatment
measure: Dose limiting toxicity
timeFrame: From enrollment of the first subject to completion of follow-up of the last subject（up to 2 years））
Secondary outcomes:
measure: Effectiveness evaluation
timeFrame: At weeks 4，8 and months 3，6，9，12，16，20 and 24 after treatment
measure: Cell continued survival time in vivo
timeFrame: At weeks 4，8 and months 3，6，9，12，16，20 and 24 after treatment
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: the first affiliated hospital of Zhejiang University，school of medicine
state: Zhejiang
Study officials:
References: