Radiotherapy With Sequential Chemotherapy Combined With PD-1 Inhibitor and Thymalfasin for BRPC

Efficacy and Safety of Radiotherapy With Sequential Chemotherapy Combined With PD-1 Inhibitor and Thymalfasin for Borderline Resectable Pancreatic Cancer

This is a prospective, single-center, single-arm, phase II clinical study. The primary purpose of the study was to evaluate the efficacy and safety of radiotherapy with sequential albumin-bound paclitaxel + Gemcitabine chemotherapy + anti-PD-1 monoclonal antibody and Thymalfasin for borderline resectable pancreatic cancer, and to explore clinical indicators related to efficacy, further guiding subsequent individualized precise treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Carcinoma, Pancreatic Ductal
• Intervention / Treatment: Combination product: SBRT with Sequential AG regimen +Tislelizumab+Thymalfasin

Detailed Description

This is a prospective, single-center, single-arm, phase II clinical study. In this study, 20 patients with borderline resectable pancreatic cancer and without any prior treatment will be enrolled. After signing the informed consent form, patients will be screened to ensure they meet the eligibility criteria.Before surgery, eligible patients will receive 4 cycles of neoadjuvant therapy: Tislelizumab combined with AG regimen and SBRT and 13 weeks of Thymalfasin therapy; after 4 cycles, the efficacy will be evaluated and radical surgery will be performed on schedule. The postoperative treatment of patients will be jointly decided by clinical physicians and patients according to the actual conditions of clinical diagnosis and treatment.

The main observation indicator is the R0 resection rate after neoadjuvant therapy; Safety assessment: The safety will be assessed after each cycle of neoadjuvant therapy and at 30 days after the last dose; Event follow-up: The events will be followed once every 3 months during the first year after surgery, and once every 6 months during the second year after surgery.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jiabin Jin, PhD; Phone Number: +86 18101870031; Email: jjb11501@rjh.com.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years, with ECOG score of 0 ~ 1;
2. Histologically or cytologically confirmed diagnosis of ductal adenocarcinoma of pancreas;
3. Classification as borderline resectable pancreatic cancer according to the NCCN Guidelines (2024 Edition);
4. Deemed suitable for neoadjuvant therapy following discussion by the MDT team of the study site;

5. Subjects must meet the following criteria for hematology test:

   1. Neutrophil count ≥ 1.5 × 10^9/L
   2. Hemoglobin ≥ 10 g/dL
   3. Platelet count ≥ 100 × 10^9/L

6. Subjects must meet the following criteria for blood chemistry tests:

   1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
   2. AST and ALT < 1.5 × ULN
   3. Creatinine clearance ≥ 60 mL/min
   4. Good coagulation, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN
7. Subjects of childbearing potential should take appropriate protective measures (contraceptive methods or other birth control methods) prior to enrollment and throughout the clinical study;
8. Has signed the informed consent form;
9. Capable of complying with the study protocol and follow-up procedures.

Exclusion Criteria:

1. Prior systemic anti-tumor therapy;
2. Prior medical history of other tumors, except for cervical carcinoma in situ, treated squamous cell carcinoma or urothelial bladder carcinoma (Ta and TIS), or other malignant tumors that have received radical treatment (at least 5 years prior to enrollment);
3. Prior history of abdominal radiotherapy;
4. Subjects with active bacterial or fungal infection (≥ Grade 2 as per NCI-CTC, Version 3).
5. Subjects with HIV, HCV, or HBV infection, uncontrollable coronary artery disease or asthma, uncontrollable cerebrovascular disease or other diseases judged by the investigator to be ineligible for enrollment;
6. Subjects with autoimmune diseases or immunodeficiency and requiring treatment with immunosuppressive agents;
7. Pregnant or lactating women; women of childbearing potential must have a negative pregnancy test results within 7 days prior to enrollment;
8. Subjects with drug abuse/clinical/psychological/social factors that affect informed consent or study conduct;
9. Subjects who may be allergic to PD-1 monoclonal antibody immunotherapy drugs;
10. Patients who are scheduled to undergo or have previously undergone organ or bone marrow transplant;
11. Patients requiring treatment with systemic corticosteroids (at dose level > 10 mg/day prednisone efficacy) or other immunosuppressive drugs within 14 days prior to the first dose or during the study. However, enrollment is permitted if: In the absence of active autoimmune disease, patients are permitted to use topical or inhaled steroids, or adrenal hormone replacement therapy at dose level ≤ 10 mg/day prednisone efficacy;
12. Treatment with live vaccines within 28 days prior to the first dose; except for inactivated viral vaccines for seasonal influenza;
13. Active pulmonary tuberculosis;
14. Treatment with related drugs or medical technology affecting immunity within 6 months prior to the first dose (including but not limited to: thymopentin, thymalfasin, interferon, CAR-T therapy, etc.);
15. Patients with other conditions unsuitable for this clinical trial judged by the investigator.

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: CRT+PD-1 inhibitor+Thymalfasin; All eligible 20 subjects will receive a neoadjuvant therapy regimen of chemoradiotherapy combined with anti-PD-1 monoclonal antibody and Thymalfasin.

Combination product: SBRT with Sequential AG regimen +Tislelizumab+Thymalfasin; Stereotactic body radiation therapy (SBRT): 30 ~ 40 Gy/5f, Week 1, Day 1 ~ Day 5, 6-8 Gy/time, once a day; 3 weeks as a cycle, for 4 cycles Tislelizumab: 200 mg, i.v., single infusion, 21 days as a cycle for 4 cycles, on Day 1 of each treatment cycle; Thymalfasin: 4.8 mg, subcutaneous injection, twice a week, on Day 1 and Day 4 of each week during Weeks 1 ~ 13; Albumin-bound paclitaxel: 125 mg/m2, i.v., on Day 1 and Day 8 of each treatment cycle; Gemcitabine: 1000mg/m2, i.v., on Day 1 and Day 8 of each treatment cycle; After 4 cycles of preoperative neoadjuvant therapy, radical surgery will be evaluated by the MDT team within 2-4 weeks after completion of chemotherapy + immunotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	Defined as the proportion of patients in the ITT population who undergo R0 resection following neoadjuvant therapy among patients undergoing surgery.	within 10 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor regression grade (TRG)	Tumor regression grade was determined according to the postoperative pathological results.	within 10 days after surgery
Pathologic complete response (pCR) rate	Defined as the proportion of patients in the ITT population who reach pT0N0M0 among patients undergoing surgery.	within 10 days after surgery
Median progression-free survival (mPFS)	The median time from the first dose to any documented tumor progression or death due to any cause (whichever occurs first) in the ITT population. Patients who are alive at the time of analysis and have no documented disease progression will be reviewed on the date of the last imaging assessment.	24 months
Median overall survival (mOS)	The median time from the first dose to death due to any cause in the ITT population. Patients who are alive at the time of analysis will be reviewed on their last contact date.	24 months
Major pathologic response (MPR) rate	Defined as the proportion of patients in the ITT population who achieve TRG1 among patients undergoing surgery.	within 10 days after surgery
Objective response rate (ORR)	Defined as the proportion of patients in the ITT population achieving complete response (CR) + partial response (PR) according to iRECIST.	Baseline (before surgery)
Disease control rate (DCR)	Defined as the proportion of subjects in the ITT population who achieve disease response and stable disease among all subjects.	Baseline (before surgery)
TRAE	Incidence of treatment-related adverse event	from commencing of treatment to the 30th day after surgery
irAE	Incidence of immune-related adverse event	from commencing of PD-1 inhibitor to the 30th day after surgery
Incidence of surgical complications	Incidence of surgical complications within 30 days after surgery	within 30 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The expression of CD68	The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC	up to 3 months after surgery
The expression of CD86	The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC	up to 3 months after surgery
The expression of CD163	The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC	up to 3 months after surgery
The expression of CD4	The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC	up to 3 months after surgery
The expression of CD8	The density, H-score of each marker in paraffin-embedded tissue sections detected by mIHC	up to 3 months after surgery

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Investigators: Principal Investigator: Jiabin Jin, PhD, Ruijin Hospital; Principal Investigator: Baiyong Shen, PhD,MD, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: August 23, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: chemotherapy; radiotherapy; PD-1 inhibitor; borderline resectable; pancreatic ductal adenocarcinoma; thymalfasin
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Ductal, Lobular, and Medullary; Pancreatic Neoplasms; Carcinoma, Ductal; Carcinoma, Pancreatic Ductal; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Adjuvants, Immunologic; Thymalfasin; Tislelizumab
• Other Study ID Numbers: ZDX+PD-1+CRT-PDAC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Export of individual patient data is a sensitive issue according to current Chinese laws.

Drug and device information, study documents

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