Safety and Feasibility of HIPEC for High-Risk Gallbladder Adenocarcinoma

Safety and Feasibility of Prophylactic Heated Intra-peritoneal Chemotherapy (HIPEC) for High-Risk Gallbladder Adenocarcinoma

Gallbladder adenocarcinoma is a devastating disease associated with a poor prognosis. Gallbladder and other biliary cancers will be responsible for an estimated 11,980 new cases, and 4,090 deaths in the US during 2020. The 5-year survival for all patients with gallbladder cancer is 18%, however this plummets to 2% for patients with metastatic disease. Patients with gallbladder cancer frequently develop peritoneal recurrence, particularly after intra-operative bile spillage during cholecystectomy for incidentally discovered gallbladder malignancy. Once developed, peritoneal metastases are difficult to treat and result in significant morbidity and mortality. As a result, novel approaches that target peritoneal metastases are needed for this disease. Prophylactic use of heated intraperitoneal chemotherapy (HIPEC) has been explored or is under active investigation for numerous gastrointestinal malignancies, including colon, gastric, and appendiceal cancers. HIPEC has efficacy in gallbladder cancer patients with macroscopic peritoneal disease undergoing cytoreductive surgery (CRS)/HIPEC and has been associated with a survival advantage in a multi-institutional retrospective case series. Incidentally discovered gallbladder cancer is treated with central hepatectomy and portal lymphadenectomy, therefore a prophylactic HIPEC can be easily incorporated into the second operation performed as part of the standard of care. In this early phase clinical trial, the investigators will explore the safety and feasibility of prophylactic HIPEC for gallbladder cancer in patients at high-risk of peritoneal recurrence. The primary endpoint is to assess feasibility of the prophylactic heated intraperitoneal chemotherapy (HIPEC) approach in gallbladder cancer. The primary endpoints include occurrence of intra-operative complications, technical challenges, 90-day postoperative morbidity and mortality, length of stay and readmission, which will be documented and compared with historical controls after follow-up.

Study Overview

• Status: Recruiting
• Conditions: Gallbladder Adenocarcinoma
• Intervention / Treatment: Drug: HIPEC

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Brian Boone, MD; Phone Number: 3045984000; Email: brian.boone@hsc.wvu.edu

Study Locations

• United States
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University Cancer Institute Mary Babb Randolph Cancer Center
      • Contact: Brian Boone, MD; Phone Number: 3045984000; Email: brian.boone@hsc.wvu.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects must have histologically or cytologically confirmed gallbladder adenocarcinoma AND inadvertent spillage of bile or intentional decompression during cholecystectomy OR tumors extending through the serosa of the gallbladder (T3/T4) OR poorly differentiated gallbladder adenocarcinoma.
• ECOG Performance status ≤ 2

• Subjects must have normal organ and marrow function as defined below:

  • Hemoglobin ≥ 10.0 g/dl
  • Leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelet count ≥ 100,000/mcL
  • Total bilirubin within normal institutional limits
  • AST (SGOT) ≤ 2.5 X institutional upper limit of normal
  • ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
  • Serum Creatinine within normal institutional limits
• Eligible TNM staging includes >T1b meeting above criteria, any N, and M0
• Eligible candidates for standard surgical management which includes central liver resection (+ cholecystectomy if not already performed) and portal lymphadenectomy
• Subjects must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior systemic therapy for gallbladder adenocarcinoma
• Subjects receiving any other investigational agents.
• Subjects with known or suspected metastatic disease
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MMC or other agents used in this study.
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding are excluded from this study because MMC has the potential for teratogenic or abortifacient effects. Because there is known risk for adverse events in nursing infants secondary to treatment of the mother with MMC, breastfeeding should be discontinued if the mother is treated with MMC.
• Subjects with past medical history of hepatitis B or C
• Subjects with evidence of biliary obstruction thought to be cancer related, including subjects requiring biliary stent

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: HIPEC; Prophylactic Heated Intra-peritoneal Chemotherapy (HIPEC) 30 mg of mitomycin C (MMC) over the first 60 minutes followed by 10 mg over an additional 30 minutes. Perfusate will be heated to obtain a tissue temperature of 42°.

Drug: HIPEC; Heated Intra-Peritoneal Chemotherapy (HIPEC) HIPEC will be performed at the time of the index operation if a cancer is known pre-operatively, at the time of re-operation for incidentally discovered cancers already treated with cholecystectomy that are undergoing central hepatectomy and portal lymphadenectomy as part of standard of care, or independently if no other procedures are indicated. A closed technique will be utilized to deliver mitomycin C (MMC) over the first 60 minutes followed by an additional smaller dose over an additional 30 minutes. Perfusate will be heated to obtain a tissue temperature of 42°; Other Names: intra-peritoneal chemotherapy; mitomycin c

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrences of intraoperative complications	Number of occurrences of intraoperative complications	During procedure
Occurrences of Postoperative Morbidity and Mortality	Number of occurrences of postoperative morbidity and mortality	90 days postoperative
Length of Stay	LOS Median	Up to 90 days
Readmission	Number of readmission occurrences	Up to 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peritoneal Metastases	Incidence of Peritoneal Metastases	Up to 5 Years
Disease Free Survival	Incidence of Disease Free Survival	Up to 5 Years

Collaborators and Investigators

• Sponsor: West Virginia University
• Investigators: Principal Investigator: Brian Boone, MD, WVU Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: June 17, 2022
• First Submitted That Met QC Criteria: June 17, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Drug Therapy; Indoles; Hyperthermia, Induced; Quinones; Azirines; Combined Modality Therapy; Mitomycins; Indolequinones; Chemotherapy, Adjuvant; Mitomycin; Hyperthermic Intraperitoneal Chemotherapy
• Other Study ID Numbers: 2202522011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes