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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Unresectable Pancreatic Cancer
• Intervention / Treatment: Drug: NRT6008 Injection + Systematic chemotherapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhaoshen Li; Phone Number: +8602131162338; Email: zhsl@vip.163.com
• Study Contact Backup: Name: Zhaoshen Li; Email: zhsl@vip.163.com

Study Locations

• China
  • Chongqing, China
    • Chongqing University Cancer Hospital
    • Contact: Weiqing Chen
    • Principal Investigator: Weiqing Chen
  • Tianjin, China
    • Tianjin Medical University General Hospital
    • Contact: Bangmao Wang
    • Principal Investigator: Bangmao Wang
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
      • Principal Investigator: Suxia Luo
      • Contact: Suxia Luo
  • Jiangsu
    • Suzhou, Jiangsu, China
      • Second Affiliated Hospital of Soochow University
      • Principal Investigator: Duanmin Hu
      • Contact: Duanmin Hu
  • Shanghai
    • Shanghai, Shanghai, China, +8602131162338
      • Shanghai Changhai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥18 years, able to comprehend and sign an informed consent form;
2. Diagnosed with pancreatic ductal adenocarcinoma confirmed histologically or cytologically;
3. Evaluated as unresectable LAPC by the investigator, or having contraindications to surgery, or refusing surgical resection;
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 ≥100 g/L, platelets ≥80×10^9/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 (e.g. >150/100 mmHg), diabetes (meeting diagnostic criteria for diabetes, e.g. fasting blood glucose ≥7.0 mmol/L, and/or postprandial blood glucose ≥11.1 mmol/L), etc.;
11. Within 6 months prior to the screening period, occurrence of acute or chronic 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 30 days prior to screening period;
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NRT6008 Injection; In this study, participants shall receive NRT6008 injection in combination with chemotherapy.

Drug: 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: oxaliplatin 85 mg/m^2, irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, and fluorouracil 2400 mg/m^2 given as a 46-hour continuous infusion, every 2 weeks (4 weeks/cycle). -NRT6008 injection administration: NRT6008 injection is implanted into pancreatic tumor via endoscopic ultrasound (EUS)-guided fine-needle injection, at the instruction of the investigator. The dose of NRT6008 injection is determined by tumor volume and estimated tumor average absorbed dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) or the recommended phase Ⅱ dose (RP2D)	Optimal dose for NRT6008 injection	28 days after NRT6008 administration
Dose-limiting toxicity (DLT)	Incidence rate of DLT	28 days after NRT6008 administration
Adverse events (AE) and severe adverse events (SAE)	Incidence rate and severity of AE and SAE	Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	According to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1 (evaluated by the investigator and Independent Review Committee respectively)	Up to 52 weeks
Duration of response (DOR)	According to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1 (evaluated by the investigator and Independent Review Committee respectively)	Up to 52 weeks
Progression-free survival (PFS)	According to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1 (evaluated by the investigator and Independent Review Committee respectively)	Up to 52 weeks
Overall survival (OS)	How long the participant lives after the administration	Up to 52 weeks
Resection rate (R0 and R1)	R0 (≥1 mm margin), R1 (<1 mm clearance)	Up to 52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of tumor biomarkers	Changes of tumor biomarkers through the study	Up to 52 weeks
Numeric rating scale (NRS) of pain	Changes of NRS score	Up to 52 weeks
Distribution of NRT6008 injection in human body and radioactivity of biological samples	Distribution of NRT6008 injection in human body and radioactivity of Yttrium-90 in blood, urine, and feces (if available)	Up to 48 hours

Collaborators and Investigators

• Sponsor: Chengdu New Radiomedicine Technology Co. LTD.
• Investigators: Principal Investigator: Zhaoshen Li, Changhai Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Estimated): February 26, 2024

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Yttrium-90; Selective internal radiation therapy; Endoscopic ultrasound-guided fine-needle injection
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: NrtPac-1; CTR20240312 (Other Identifier: Center for Drug Evaluation, NMPA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Relevant results will be selectively disclosed in the future.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No