Clinical trial NCT06278454: Safety and Efficacy of NRT6008 in Patients With Unresectable Locally Advanced Pancreatic Cancer (LAPC)
Official title: A Phase I Study to Evaluate the Safety, Tolerance and Efficacy of NRT6008 Injection in Unresectable Locally Advanced Pancreatic Cancer (LAPC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Unresectable Pancreatic Cancer
Keywords: Yttrium-90
Endoscopic ultrasound-guided fine-needle injection
Locally Advanced Pancreatic Carcinoma
Lead sponsor: Chengdu New Radiomedicine Technology Co. LTD.
Sponsor class: INDUSTRY
First posted: 2024-02-26
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single arm, open label, multi-center phase I study, including phase Ia dose escalation and phase Ib dose expansion. Safety review committee (SRC) will be formed to monitor safety and efficacy data through the study. And the independent review committee (IRC) will be formed to monitor efficacy data through the study.

Detailed description: The efficacy and safety of Yttrium-90 carbon microspheres in patients with unresectable LAPC remain unknown. This trial is a prospective, multicenter, open-label, single-arm phase I trial designed to evaluate the safety and efficacy of NRT6008 injection. The primary objective is to evaluate the safety of NRT6008 Injection. While the secondary objectives include the assessments of the preliminary efficacy. In addition, the distribution of NRT6008 injection in human body, and the changes of tumor biomarkers and the improvement of cancer pain status of participants after administration will also be evaluated.

Eligibility criteria: Inclusion Criteria:

1. Aged ≥18 years and ≤80 years, able to comprehend and sign an informed consent form;
2. Diagnosed with pancreatic adenocarcinoma confirmed histologically or cytologically;
3. Evaluated as unresectable LAPC by the investigator, or having contraindications to surgery, or refusing surgical resection (only patients with non-regional lymph node metastasis are eligible);
4. ECOG performance status score ≤1;
5. Expected survival ≥3 months;
6. According to RECIST v1.1 criteria, there is only one measurable lesion in the pancreas confirmed by imaging, and the lesion has the shortest axis diameter ≥2.0 cm, the longest axis diameter ≤6.0 cm (based on baseline imaging);
7. Adequate normal organ and marrow function as defined below: (1) Renal function: serum creatinine ≤1.5×ULN, or creatinine clearance ≥60 mL/min (calculated by the Cockcroft-Gault formula); (2) Liver function: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3×ULN; serum total bilirubin ≤1.5×ULN; (3) Bone marrow function \[\[no blood transfusion or granulocyte colony-stimulating factor (G-CSF), human thrombopoietin (TPO), or TPO receptor agonist treatment within 14 days prior to signing informed consent\]: neutrophils ≥1.5×10\^9/L, hemoglobin ≥90 g/L, platelets ≥100×10\^9/L; (4) Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5×ULN;
8. Female and male participants of reproductive age must voluntarily agree to practice strict and effective contraception after signing the informed consent form, during the study period, and within 12 months after administration of the investigational drug. Males are prohibited from donating sperm during this period. Female participants of reproductive age must have a negative pregnancy test result during the screening period and within 24 hours before administration of the investigational drug.

Exclusion Criteria:

1. Allergic to the investigational drug NRT6008 injection itself or any of its components;
2. Contraindications to any of the three optional systemic chemotherapy regimens in this study judged by investigators;
3. Previous anti-tumor treatments for pancreatic cancer, including but not limited to chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc. Except for discontinuation of traditional chinese medicine or herbal medicine for at least 7 days prior to the screening period;
4. Contraindications to anesthesia;
5. History of any other malignant tumors within 5 years before receiving investigational drug treatment, except for cases of cured non-melanoma skin cancer, cervical carcinoma in situ, or basal cell carcinoma of the skin, Stage I Grade 1 endometrial carcinoma, or thyroid cancer;
6. Presence or suspected presence of distant metastases according to imaging;
7. Pregnant or lactating females;
8. Participants assessed by the investigators to be at high risk or had difficulty in operation for EUS-FNI procedures;
9. Evidence of radiographic invasion into stomach, duodenum or peritoneum;
10. Participants with chronic diseases that are actively treated but not well controlled, such as primary hypertension, diabetes, etc.;
11. Within 6 months prior to the the first administration of chemotherapy, occurrence of acute pancreatitis, severe gastrointestinal bleeding, severe cardiovascular diseases (including but not limited to stroke, unstable angina), or occurrence of acute infections requiring systemic treatment within 2 weeks before the screening period;
12. Participated in other interventional clinical trials within 1 month prior to the first administration of chemotherapy;
13. Positive for human immunodeficiency virus (HIV) antibodies;
14. Positive for hepatitis B virus (HBV) surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb), HBV DNA testing required, participants with HBV-DNA levels below the lower limit of the reference range or \< 500 IU/mL will be eligible for inclusion in this study (use of antiviral drugs during the study period is required);
15. Positive for hepatitis C virus (HCV) antibodies, HCV RNA testing required, participants with negative HCV RNA results will be eligible for inclusion in this study;
16. Participants with syphilis infection or active tuberculosis;
17. Other reasons deemed unsuitable for participation in this trial by the investigators.

Primary outcomes:
measure: Maximum tolerated dose (MTD) or the recommended phase Ⅱ dose (RP2D)
timeFrame: 28 days after NRT6008 administration
measure: Dose-limiting toxicity (DLT)
timeFrame: 28 days after NRT6008 administration
measure: Adverse events (AE) and severe adverse events (SAE)
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 52 weeks
measure: Duration of response (DOR)
timeFrame: Up to 52 weeks
measure: Progression-free survival (PFS)
timeFrame: Up to 52 weeks
measure: Overall survival (OS)
timeFrame: Up to 52 weeks
measure: Resection rate (R0 and R1)
timeFrame: Up to 52 weeks
Other outcomes:
measure: Concentration of tumor biomarkers
timeFrame: Up to 52 weeks
measure: Numeric rating scale (NRS) of pain
timeFrame: Up to 52 weeks
measure: Distribution of NRT6008 injection in human body and radioactivity of biological samples
timeFrame: Up to 48 hours
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Suzhou
country: China
facility: Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai General Hospital
state: Shanghai
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
Study officials:
affiliation: Changhai Hospital
name: Zhaoshen Li
role: PRINCIPAL_INVESTIGATOR
References: