Selective Transvenous Chemoembolization of Primary Pancreatic Tumors

Catheter directed retrograde venous infusion of gemcitabine/lipiodol into pancreatic tumors.

Study Overview

• Status: Withdrawn
• Conditions: Pancreatic Adenocarcinoma
• Intervention / Treatment: Drug: Retrograde venous infusion of gemcitabine/lipiodol

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)]

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: Pancreatic adenocarcinoma; 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; 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.; Other Names: Pancreatic retrograde venous infusion (PRVI)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Robert P Liddell, MD, Johns Hopkins School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2019
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: March 5, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Actual): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 22, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: chemotherapy; gemcitabine; retrograde venous infusion; lipiodol
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Ethiodized Oil
• Other Study ID Numbers: J1936; IRB00164996 (Other Identifier: JHM IRB)

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