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

Unresectable Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06278454
• Other study ID #: NrtPac-1
• Secondary ID: CTR20240312
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: March 2024
• Est. completion date: December 2026

Study information

• Verified date: January 2024
• Source: Chengdu New Radiomedicine Technology Co. LTD.
• Contact: Zhaoshen Li
• Phone: +8602131162338
• Email: zhsl[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 58
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Neoplasms
• Unresectable Pancreatic Cancer

Intervention

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.

Locations

Country	Name	City	State
China	Chongqing University Cancer Hospital	Chongqing
China	Shanghai Changhai Hospital	Shanghai	Shanghai
China	Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tianjin Medical University General Hospital	Tianjin
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chengdu New Radiomedicine Technology Co. LTD.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Concentration of tumor biomarkers	Changes of tumor biomarkers through the study	Up to 52 weeks
Other	Numeric rating scale (NRS) of pain	Changes of NRS score	Up to 52 weeks
Other	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
Primary	Maximum tolerated dose (MTD) or the recommended phase ? dose (RP2D)	Optimal dose for NRT6008 injection	28 days after NRT6008 administration
Primary	Dose-limiting toxicity (DLT)	Incidence rate of DLT	28 days after NRT6008 administration
Primary	Adverse events (AE) and severe adverse events (SAE)	Incidence rate and severity of AE and SAE	Up to 52 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall survival (OS)	How long the participant lives after the administration	Up to 52 weeks
Secondary	Resection rate (R0 and R1)	R0 (=1 mm margin), R1 (<1 mm clearance)	Up to 52 weeks