Implantation of iodine125-Seeds Combined With Chemotherapy in the Treatment of Metastatic Pancreatic Carcinoma

Study Overview
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Brief Summary
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The goal of this clinical trial is to evaluate the clinical efficacy and safety of endoscopic ultrasonography (EUS)-guided radioactive iodine 125 seeds in combination with AG regimen chemotherapy for the treatment of metastatic pancreatic cancer. The main questions it aims to answer are: whether the combination of minimally invasive endoscopy-guided local radiation therapy with chemotherapy may improve overall survival the adverse events of the combination therapy Participants will receive the implantation of radioactive seeds under EUS guide. 48h after implantation, chemotherapy with Gem/nab-P given on days 1 and 8 of each 21-day cycle will be conducted. Researchers will compare the I125+AG group with the group that takes AG chemotherapy alone to see if the overall survival can be improved.

Official Title
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Endoscopic Ultrasound-guided Intratumoral Iodine125-Seeds Implantation Combined With Gem/Nab-P Chemotherapy Versus Gem/Nab-P Alone for Metastatic Pancreatic Carcinoma: a Randomized, Controlled, Trial

Conditions
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Metastatic Pancreatic Cancer

Intervention / Treatment
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* Procedure: Iodine125-Seeds implantation
* Drug: Gem/nab-P Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (Before the trial, subjects must meet all of the requirements listed below in order to be enrolled) 18 to 80 years old; Stage IV pancreatic ductal adenocarcinoma with distant metastases confirmed by clinical, imaging, and pathology, and the primary and metastatic mass can be measured on imaging. No treatment history of chemotherapy, radiotherapy, or surgery Expected survival > 6 months ECGO score of 0-2 Eligible for chemotherapy (white blood cell > 3.5×109/L, neutrophil value > 1.5×109/L, hemoglobin > 80g/L, platelets > 100×109/L, albumin > 25g/L, alanine aminotransferase or aspartate aminotransferase ≤ 3 times the upper limit of normal and total bilirubin level ≤ 34.2umol/L, creatinine < 176.8 umol/L, normal ECG) Signed written informed consent; Exclusion Criteria: Contraindication of EUS-guide procedure or technical infeasibility (e.g.,coagulation disorder, anatomical changes, large vessels along the puncture path) Pregnant or breastfeeding Presence of brain metastases Presence of deep vein thrombosis or pulmonary embolism Presence of HIV, HBV, HCV infection or other uncontrollable active infection Hypersensitivity to chemotherapy drugs History of other malignancies within 5 years Peripheral neuropathy or interstitial lung disease within 5 years Patient is enrolled in any other clinical protocol or investigational trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: I125-AG<br>Participants will receive the implantation of radioactive seeds under EUS guide. 48h after implantation, chemotherapy with Gemcitabine 1000mg/m2 plus albumin paclitaxel 125mg/m2 given on days 1 and 8 of each 21-day cycle will be conducted. | Procedure: Iodine125-Seeds implantation<br>* Endoscopic ultrasound-guided intratumoral iodine125-Seeds implantation<br>Drug: Gem/nab-P Chemotherapy<br>* nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8 every 3 weeks<br>|
| Active Comparator: AG<br>Participants receive chemotherapy alone. Gemcitabine 1000mg/m2 plus albumin paclitaxel 125mg/m2 given on days 1 and 8 of each 21-day cycle. | Drug: Gem/nab-P Chemotherapy<br>* nab-paclitaxel (125 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter) on days 1, 8 every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is defined as the time from the date of randomization to the date of death (any cause). Patients who are alive will be censored at the last known time that the patient was alive. | 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of Adverse events (AEs) | AEs are graded and reported using The CTCAE version 5.0. | 48 months | 
| Progression-free survival (PFS) | PFS is defined as the time from the date of randomization to the date of objective disease progression according to RECIST 1.1 criteria or death (due to any cause),whichever occurs first. | 48 months | 
| Overall Response Rate (ORR) | ORR is defined as the percentage of patients with an investigator-assessed complete (CR) or partial response (PR) according to RECIST v1.1. | 48 months | 
| CA19-9 response | CA19-9 response is defined as a decrease of CA19-9 concentration by 50% from the prespecified baseline concentration of 74 U/mL or more. | 48 months | 
| Metabolic response | Metabolic response is evaluated by PET/CT according to EORTC criteria. | from baseline to the end of 2nd chemotherapy cycle | 
| Visual analog scale (VAS) | Pain is scored according to a VAS score, with a score of 0 indicating no pain and a score of 10 indicating the most intense degree of pain (unbearable pain). | 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iodine 125, EUS-guided implantation, chemotherapy