Nimotuzumab Combined With Nab-paclitaxel/Gemcitabine in the Perioperative Treatment of High-risk Resectable/Borderline Resectable Pancreatic Cancer (NOTABLE-309)

Randomized Double-blind, Placebo-controlled, Multicenter Clinical Study of Nimotuzumab Combined With Nab-paclitaxel/Gemcitabine in the Perioperative Treatment of High-risk Resectable/Borderline Resectable Pancreatic Cancer

This is a prospective, multicenter, randomized, double-blind, placebo-controlled study. The main purpose of the study is to evaluate the clinical efficacy and safety of Nimotuzumab combined with nab-paclitaxel plus gemcitabine (AG) in the perioperative treatment of high-risk resectable/borderline resectable pancreatic cancer.

Study Overview

• Status: Withdrawn
• Conditions: Pancreatic Cancer, Adult
• Intervention / Treatment: Drug: Nimotuzumab; Drug: AG regimen; Drug: Placebo

Detailed Description

This clinical study is designed as a prospective, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy and safety of Nimotuzumab combined with nab-paclitaxel plus gemcitabine (AG) in the perioperative treatment of high-risk resectable/borderline resectable pancreatic cancer. About 156 patients will be enrolled in this study and randomly divided into experimental group (nimotuzumab plus AG) and control group (placebo plus AG) at a ratio of 1:1. The main endpoint is disease-free survival (DFS). Additional end points include overall survival (OS), R0 resection rate, preoperative objective response rate (ORR), postoperative complications and safety, etc.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100000
      • Beijing Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • The First Affiliated Hospital with Nanjing Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Age 18-75 years old, gender unlimited;
• 2. Histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC);
• 3. Confirmed as resectable/borderline resectable pancreatic cancer by CT/MRI imaging (resectability assessment refers to the NCCN criteria). If it is resectable pancreatic cancer, any of the following high-risk factors should also be met: 1) Carbohydrate Antigen 19-9(CA199) > 500 U/ml; 2) the maximum diameter of the primary tumor > 3.0 cm; 3) severe weight loss; 4) Extreme pain; regional lymph node metastasis (N1 or N2);
• 4. Voluntarily accept sample collection (for KRAS gene testing and subsequent analysis);
• 5. Adequate organ and bone marrow function, defined as follows: hemoglobin≥9.0 g/dL; absolute neutrophil count (ANC)≥1.5×10^9/L; platelets≥80×10^9/L; serum total bilirubin (TBIL)≤1.5×ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN); serum creatinine≤1.5×ULN or estimated creatinine clearance > 60 mL/min;
• 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2;
• 7. Life expectancy of at least 3 months;
• 8. Women of childbearing age should have a negative result of serum human chorionic gonadotropin (HCG) test or urine pregnancy test within 72 hours prior to randomization (Postmenopausal women who have had amenorrhea for at least 12 months are considered sterile and women known to have had tubal ligation are not required to undergo pregnancy tests);
• 9. Good compliance and signed informed consent.

Exclusion Criteria:

• 1. Previous treatment for pancreatic cancer.
• 2. Accompanied by other serious diseases, including but not limited to: active infections; unmanageable diabetes mellitus and uncontrolled hypertension (Systolic Blood Pressure>160mmHg or Diastolic Blood Pressure>100mmHg); compensatory heart failure (New York Heart Association (NYHA) grade III and IV), unstable angina or poorly controlled arrhythmias within 3 months prior to randomization; presence of uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage; severe portal hypertension; digestive tract obstruction; respiratory insufficiency and severe lung disease; central nervous system disease or mental illness;
• 3. Clinically diagnosed as local recurrence of pancreatic cancer, or there is evidence of peritoneal/other distant metastases;
• 4.History of other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix);
• 5. bleeding or clotting disorder;
• 6. Known allergy to prescription or any component of the prescription used in this study;
• 7. With human immunodeficiency virus (HIV) or syphilis infection, or active hepatitis (hepatitis B, hepatitis C);
• 8. Women who are pregnant or are breastfeeding;
• 9.Other reasons that are not suitable to participate in this study according to the researcher's judgment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nimotuzumab+ AG	Drug: Nimotuzumab; Patients will receive 3 cycles of neoadjuvant treatment with Nimotuzumab (400 mg on days 1, 8, and 15 of a 21-day cycle), followed by surgery and 5 cycles of adjuvant Nimotuzumab (400 mg on days 1, 8, and 15 of a 21-day cycle).; Drug: AG regimen; Patients will receive 3 cycles of AG (gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2 on days 1 and 8 of a 21-day cycle), followed by surgery and 5 cycles of adjuvant AG (gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2 on days 1 and 8 of a 21-day cycle).
Placebo Comparator: Placebo+ AG	Drug: AG regimen; Patients will receive 3 cycles of AG (gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2 on days 1 and 8 of a 21-day cycle), followed by surgery and 5 cycles of adjuvant AG (gemcitabine 1000 mg/m^2 and nab-paclitaxel 125 mg/m^2 on days 1 and 8 of a 21-day cycle).; Drug: Placebo; Patients will receive 3 cycles of neoadjuvant treatment with placebo (400 mg on days 1, 8, and 15 of a 21-day cycle), followed by surgery and 5 cycles of adjuvant therapy (placebo 400 mg on days 1, 8, and 15 of a 21-day cycle).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
disease-free survival (DFS)	The time from the date of surgery to the disease recurrence or death, whichever is earlier.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events	Frequency and severity of adverse events.	Up to 30 days after last administration
overall survival (OS)	The time from the date of randomization to death due to any cause.	Up to 24 months
R0 resection rate	Pathologic review will determine if an R0 resection has been performed. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.	within 30 days after surgery
Surgical Resection rate	Patients who undergo surgical resection will be documented.	within 30 days after surgery
Objective response rate (ORR)	Objective response rate (ORR), including complete response (CR) and partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions.	Up to 9 weeks during the neoadjuvant treatment]

Collaborators and Investigators

• Sponsor: Biotech Pharmaceutical Co., Ltd.
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): January 20, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): January 17, 2025

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: resectable pancreatic cancer; Nimotuzumab; borderline resectable pancreatic cancer
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic cancer, adult; Antineoplastic Agents, Immunological; Antineoplastic Agents; nimotuzumab
• Other Study ID Numbers: IST-Nim-PC-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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