Safety and Efficacy of NRT6008 in Patients With Unresectable Locally Advanced Pancreatic Cancer (LAPC) and Advanced Pancreatic Cancer With Lymph Node Metastases

Официальное название

A Phase I Study to Evaluate the Safety, Tolerance and Efficacy of NRT6008 Injection in Unresectable Locally Advanced Pancreatic Cancer (LAPC) and Advanced Pancreatic Cancer With Lymph Node Metastases

Обзор

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.

Подробное описание

The efficacy and safety of Yttrium-90 carbon microspheres in patients with unresectable LAPC or advanced pancreatic cancer with lymph node metastases 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.

Вмешательства

• Препарат NRT6008 Injection + Systematic chemotherapy
  -Systematic chemotherapy The chemotherapy regimen is selected by the investigators at the consideration of participants' conditions, with either GN or (m)FOLFIRINOX. GN: gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, every 21 days (3 weeks/cycle). FOLFIRINOX: oxaliplatin 85 mg/m\^2, irinotecan 180 mg/m\^2, leucovorin 400 mg/m\^2 and fluorouracil 400 mg/m\^2 given as a bolus followed by 2400 mg/m\^2 given as a 46-hour continuous infusion, every 2 weeks (4 weeks/cycle). mFOLFIRINOX: o

Первичные конечные точки

• Maximum tolerated dose (MTD) or the recommended phase Ⅱ dose (RP2D) [Срок оценки: 28 days after NRT6008 administration]
• Dose-limiting toxicity (DLT) [Срок оценки: 28 days after NRT6008 administration]
• Adverse events (AE) and severe adverse events (SAE) [Срок оценки: Up to 52 weeks]

Вторичные конечные точки (5)

• Objective response rate (ORR) [Срок оценки: Up to 52 weeks]
• Duration of response (DOR) [Срок оценки: Up to 52 weeks]
• Progression-free survival (PFS) [Срок оценки: Up to 52 weeks]
• Overall survival (OS) [Срок оценки: Up to 52 weeks]
• Resection rate (R0 and R1) [Срок оценки: Up to 52 weeks]

Критерии участия

Критерии включения

• Aged ≥18 years and ≤80 years, able to comprehend and sign an informed consent form;
• Diagnosed with pancreatic adenocarcinoma confirmed histologically or cytologically;
• Evaluated as unresectable LAPC or metastatic pancreatic cancer with lymph node metastasis only, as determined by the investigator; or having contraindications to surgery, or refusing surgical resection;
• ECOG performance status score ≤1;
• Expected survival ≥3 months;
• 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);
• 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;
• 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.

Критерии исключения

• Allergic to the investigational drug NRT6008 injection itself or any of its components;
• Contraindications to any of the three optional systemic chemotherapy regimens in this study judged by investigators;
• 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;
• Contraindications to anesthesia;
• 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;
• Presence or suspected presence of distant metastases according to imaging;
• Pregnant or lactating females;
• Participants assessed by the investigators to be at high risk or had difficulty in operation for EUS-FNI procedures;
• Evidence of radiographic invasion into stomach, duodenum or peritoneum;
• Participants with chronic diseases that are actively treated but not well controlled, such as primary hypertension, diabetes, etc.;
• 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;
• Participated in other interventional clinical trials within 1 month prior to the first administration of chemotherapy;
• Positive for human immunodeficiency virus (HIV) antibodies;
• 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);
• 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;
• Participants with syphilis infection or active tuberculosis;
• Other reasons deemed unsuitable for participation in this trial by the investigators.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 6 центров

• Henan Cancer Hospital — Чжэнчжоу
• Second Affiliated Hospital of Soochow University — Сучжоу
• Shanghai Changhai Hospital — Шанхай
• Shanghai General Hospital — Шанхай
• Chongqing University Cancer Hospital — Чунцин
• Tianjin Medical University General Hospital — Тяньцзинь

Идентификаторы

NCT: NCT06278454 · NrtPac-1 · CTR20240312

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)
• NMPA/CDE CTR20240312 (платформа chinadrugtrials.org.cn)

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