Selective Transvenous Chemoembolization of Primary Pancreatic Tumors

Study Overview
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Brief Summary
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Catheter directed retrograde venous infusion of gemcitabine/lipiodol into pancreatic tumors.

Detailed Description
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Overall, subjects with resectable, borderline-resectable and/or locally-advanced pancreatic cancer are eligible to be entered into the study. Each enrolled study subject will receive a single neoadjuvant pancreatic retrograde venous infusion (PRVI) administration of the gemcitabine/Lipiodol® emulsion. Complete enrollment in 12 months from date of enrollment of first study subject.

Official Title
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Selective Transvenous Chemoembolization of Primary Pancreatic Tumors

Conditions
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Pancreatic Adenocarcinoma

Intervention / Treatment
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* Drug: Retrograde venous infusion of gemcitabine/lipiodol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Pathologically and radiologically-confirmed pancreatic adenocarcinoma confined to the pancreas with initial diagnosis within 8 weeks of consent Resectable, borderline-resectable or locally-advanced primary pancreatic adenocarcinoma per NCCN guidelines The patient is deemed a candidate for the study by the Johns Hopkins Multidisciplinary Pancreatic Tumor Board Preserved liver function (Child-Pugh A-B class) without significant liver decompensation Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at study entry Measurable or evaluable disease that will be directly treated with intra-pancreatic therapy (as defined by Response Evaluation Criteria in Solid Tumors [RECIST 1.1] Suitable for PRVI, based on blood parameters such as platelet count, LFTs including bilirubin and coagulation status including international normalized ratio (see Exclusion Criteria below) The patient is able to give informed consent The patient, if a woman of childbearing potential, has a negative pregnancy test The patient is willing and able to comply with study procedures, scheduled visits, and treatment plans Life expectancy of at least 3 months Exclusion Criteria: Serum total bilirubin > 3.0 mg/dL Creatinine > 2.0 mg/dL Platelets < 75,000/μL Hgb < 8.0 g/dl ANC ≤ 1,000/μL INR > 2.0 Complete portal vein thrombosis or significant cavernous transformation of the portal vein Ascites (trace ascites on imaging is OK) The patient is pregnant or breast-feeding The patient is allergic to contrast media that cannot be readily managed or prevented with premedication Patients with peripheral neuropathy [> grade 1, according to the National Cancer Institute Common Toxicity Criteria v5.0 (CTAE v5.0)]

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label, single institution, single-arm pilot study, designed to assess the feasibility, safety and efficacy of retrograde venous infusion of gemcitabine/Lipiodol® administered in a neoadjuvant setting for the treatment of patients with resectable, borderline-resectable or locally-advanced pancreatic adenocarcinoma.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pancreatic adenocarcinoma<br>Participants with resectable, borderline-resectable or locally-advanced pancreatic adenocarcinoma will receive pancreatic retrograde venous infusion of gemcitabine/lipiodol | Drug: Retrograde venous infusion of gemcitabine/lipiodol<br>* Access will be gained into the portal vein via a transhepatic approach. The pancreatic tumor-draining veins will be accessed via a catheter positioned in the portal vein, superior mesenteric vein or splenic vein. The catheter is then advanced into the vein draining the segment in which the targeted tumor is located. Tumor location and its venous drainage will be confirmed with sub-selective pancreatic venography and cone-beam CT. Once correct catheter positioning is confirmed, the gemcitabine/Lipiodol® emulsion will be administered under real-time fluoroscopic guidance until the entire dose is administered or until stasis is achieved in the vein through which the drug is being delivered.<br>* Other names: Pancreatic retrograde venous infusion (PRVI);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility as determined by technical success of Pancreatic Retrograde Venous Infusion (PRVI) with gemcitabine and Lipiodol® | Technical success is measured as number of participants who did not experience technical failure, which is defined as the inability to administer the gemcitabine/ Lipiodol® to the targeted pancreatic tumor. | 30 days | 
| Safety as measured by number of participants with Grade 3, 4, and 5 toxicities | Number of participants with Grade 3, 4, and 5 toxicities as defined by the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; Version 5.0) that occur during and within 30 days after PRVI | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as assessed by Objective tumor response | Objective tumor response is measured as number of participants with response as determined by RECIST 1.1 criteria to assess change in tumor size and percent tumor enhancement as visualized on pancreatic protocol CT scans. | 30 days | 
| Efficacy as assessed by change in serum CA19-9 | Change in serum CA19-9 measurements pre- and post-PRVI. | Change from baseline to 30 days | 
| Efficacy as assessed by change in levels of gemcitabine and dFdu in peripheral blood samples | Change in levels of gemcitabine and its inactive metabolite 2',2'-Difluorodeoxyuridine (dFdU) found in peripheral blood samples pre-and post-PRVI. | Change from baseline to 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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retrograde venous infusion, chemotherapy, gemcitabine, lipiodol