Selective Transvenous Chemoembolization of Primary Pancreatic Tumors

• ClinicalTrials.gov Identifier: NCT03865563
• Recruitment Status: Withdrawn
• First Posted: March 7, 2019
• Last Update Posted: January 27, 2020
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Pancreatic Adenocarcinoma	Drug: Retrograde venous infusion of gemcitabine/lipiodol	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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)
• Primary Purpose: Treatment
• Official Title: Selective Transvenous Chemoembolization of Primary Pancreatic Tumors
• Estimated Study Start Date: July 2019
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

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 Name: Pancreatic retrograde venous infusion (PRVI)

Outcome Measures

Primary Outcome Measures :

1. Feasibility as determined by technical success of Pancreatic Retrograde Venous Infusion (PRVI) with gemcitabine and Lipiodol® [ Time Frame: 30 days ]
   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.
2. Safety as measured by number of participants with Grade 3, 4, and 5 toxicities [ Time Frame: 30 days ]
   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

Secondary Outcome Measures :

1. Efficacy as assessed by Objective tumor response [ Time Frame: 30 days ]
   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.
2. Efficacy as assessed by change in serum CA19-9 [ Time Frame: Change from baseline to 30 days ]
   Change in serum CA19-9 measurements pre- and post-PRVI.
3. Efficacy as assessed by change in levels of gemcitabine and dFdu in peripheral blood samples [ Time Frame: Change from baseline to 30 days ]
   Change in levels of gemcitabine and its inactive metabolite 2',2'-Difluorodeoxyuridine (dFdU) found in peripheral blood samples pre-and post-PRVI.

Eligibility Criteria

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

Criteria

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)]

Contacts and Locations

Locations

United States, Maryland

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Robert P Liddell, MD; Johns Hopkins School of Medicine

More Information

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT03865563
• Other Study ID Numbers: J1936; IRB00164996 ( Other Identifier: JHM IRB )
• First Posted: March 7, 2019
• Last Update Posted: January 27, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:

retrograde venous infusion; chemotherapy; gemcitabine; lipiodol

Additional relevant MeSH terms:

Pancreatic Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; Ethiodized Oil; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs