Tripegfilgrastim Trial to Reduce the Risk of Severe Neutropenia in Patients With Unresectable Pancreaticobiliary Cancers

Study Overview
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Brief Summary
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Clinical trial phase: Phase 2 Intervention model: Control group Group allocation: Randomized controlled trial Research perspective: Prospective study Participating centers: Multicenter study Definition of the intervention period: Based on the RECIST 1.1 guidelines, patients will receive treatment until dropout due to disease progression or unacceptable toxicity related to the trial drug. Patients will be followed up with to assess survival every 2 months until either death or the end of the trial, whichever is first. The intervention period is from the date of IRB approval to December 31st, 2025 The follow-up duration is one year, and the statistical analysis duration is six months The total research period is from the date of IRB approval to June 30th, 2026

Detailed Description
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Pancreatic cancer and Bile duct cancer are the 8th and 9th leading causes of all cancer in Korea, have 5-year survival rates of approximately 20%, and unresectable cancers show a poor prognosis of approximately 5%. The first-line treatment recommended for unresectable pancreaticobiliary cancer is chemotherapy. FOLFIRINOX or gemcitabine/nab-paclitaxel combination therapy is recommended for pancreatic cancer, and gemcitabine/cisplatin combination therapy is recommended for bile duct cancer. Recently, anticancer therapy advances have led to an increase in survival for pancreaticobiliary cancer patients, and more than half of patients receive secondary chemotherapy due to disease progression after first-line treatment. Recently, with the introduction of nanoliposomal irinotecan (nal-IRI) and the clinical outcomes of Phase 3 NAPOL-1 trial and the Phase 2b NIFTY trial, nal-IRI/5-FU/LV combination therapy is being used as second-line chemotherapy following gemcitabine treatment. Granulocyte colony-stimulating factors (G-CSFs) (filgrastim, pegfilgrastim, and tripegfilgrastim) can be used for neutropenia prevention and treatment. In particular, pegylated G-CSF can reduce patient discomfort due to its long retention time. In a retrospective study analyzing the use of G-CSF for primary neutropenia prevention in Korea, pancreatic cancer patients who received FOLFIRINOX treatment that exhibited neutropenia and FN were significantly reduced from 55.6% to 31.6% (P = 0.003) and from 18.5% to 1.8% (P = 0.002), respectively. Similarly, in a retrospective study in Japan, preventive pegylated G-CSF treatment reduced the incidence of FN from 23% to 0%, and in a double-blinded, randomized, phase 3 breast cancer clinical trial, pegylated G-CSF treatment significantly reduced the incidence of FN from 68.8% to 1.2%. In a retrospective study of non-small cell lung cancer, another solid cancer, the incidence of FN in the preventive pegylated G-CSF treatment group was 0%, compared to an incidence of 50% in the control group. However, no studies have evaluated the efficacy of G-CSF in pancreaticobiliary cancer patients receiving nal-IRI/5-FU/LV combination therapy yet. Hence, our objective was to report the effects of pegylated G-CSF on preventing severe neutropenia in patients receiving nal-IRI/5-FU/LV combination chemotherapy for unresectable pancreaticobiliary cancer.

Official Title
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An Open-label, Randomized, Multicenter, Phase II Tripegfilgrastim Trial to Reduce the Risk of Severe Neutropenia in Patients With Unresectable Pancreaticobiliary Cancers

Conditions
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Unresectable Pancreatic Cancer, Unresectable Bile Duct Carcinoma, Unresectable Biliary Tract Carcinoma

Intervention / Treatment
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* Drug: Tripegfilgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged at least 19 years old, diagnosed with unresectable pancreaticobiliary cancer, and scheduled to receive chemotherapy using nal-IRI/5-FU/LV combination chemotherapy Exclusion Criteria: Patients who refuse to sign the consent form Patients who have previously experienced severe neutropenia during chemotherapy

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Clinical trial phase: Phase 2 Group allocation: Randomized controlled trial Research perspective: Prospective study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Premedication: depending on the center (Ondansetron 8 mg +Dextrose 5% 50 mL, MIV, Dexamethason 10 mg IV, and Atropine sulfate 0.25 mg [0.5 amp] SC) Onivyde 70 mg/m2 + Dextrose 5% 500 mL (bag), and MIV for 90 min Leucovorin 400 mg/m2 + Dextrose 5% 500 mL (bag), and MIV for 30 min 5-FU (2400 mg/m2) + Dextrose 5% 500 mL (bag) and MIV for 46 h Tripegfilgrastim 6 mg SC administered 24 h after completing 5-FU infusion The above chemotherapy will be administered every two weeks | Drug: Tripegfilgrastim<br>* Tripegfilgrastim to reduce the risk of severe neutropenia in patients with unresectable pancreaticobiliary cancers<br>* Other names: Dulastin;|
| No Intervention: Control Group<br>Premedication: depending on center (Ondansetron 8 mg+Dextrose 5% 50 mL, MIV, Dexamethason 10 mg IV, and Atropine sulfate 0.25 mg [0.5 amp] SC) Onivyde 70 mg/m2 + Dextrose 5% 500 mL (bag), and MIV for 90 min Leucovorin 400 mg/m2 + Dextrose 5% 500 mL (bag), and MIV for 30 min 5-FU (2400 mg/m2) + Dextrose 5% 500 mL (bag), and MIV for 46 h The following medication will be provided in the event that the patient develops febrile neutropenia after the above chemotherapy Tripegfilgrastim 6 mg SC administered 24 h after stopping 5-FU. In the event of neutropenia, chemotherapy will be paused until the patient recovers, and then restarted after recovery. The above chemotherapy will be administered every two weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint | Severe neutropenia incidence | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| neutropenia incidence | All grades of neutropenia incidence | through study completion, an average of 1 year | 
| Febrile neutropenia | Febrile neutropenia incidence | through study completion, an average of 1 year | 
| emergency department visits | Frequency of unexpected emergency department visits and length of stay | through study completion, an average of 1 year | 
| Overall survival | Overall survival | through study completion, an average of 1 year | 
| Progression-free survival | Progression-free survival | through study completion, an average of 1 year | 
| biomarkers | Predictive biomarkers for treatment response analysis | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unresectable Pancreatic Cancer, Unresectable Bile Duct Carcinoma, Unresectable Biliary Tract Carcinoma