HIPEC As Neoadjuvant Treatment For Resectable Pancreatic Adenocarcinoma

Study Overview

HIPEC as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma

This single-center, prospective proof-of-concept study is designed to evaluate the surgical outcomes and clinicopathologic results of neoadjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in conjunction with perioperative systemic chemotherapy (SCT; neoadjuvant and adjuvant) and pancreaticoduodenectomy (PD) in a small cohort of patients having T1-T3 resectable pancreatic ductal adenocarcinoma (PDAC) with one or more high-risk clinical features. The investigators hypothesize that HIPEC administered in this clinical course will reduce postoperative peritoneal disease recurrence. The investigators also expect that local recurrence of disease will be reduced. The primary aim of this study is to compare 2-year peritoneal disease-free survival between patients receiving the experimental therapy (neoadjuvant HIPEC + SCT + PD) with historical controls receiving standard therapy (SCT + PD). Secondary aims are to determine the clinical feasibility and outcomes of neoadjuvant HIPEC for resectable PDAC using patient demographics and disease characteristic data.

N/A

Pancreatic Neoplasms
Pancreatic Adenocarcinoma

PROCEDURE: Hyperthermic intraperitoneal chemotherapy
PROCEDURE: Open pancreaticoduodenectomy
DRUG: Gemcitabine

02-16-05A

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-07-25	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-04-20
First Submitted that Met QC Criteria 2016-07-27	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-04-27
First Posted (ACTUAL) 2016-08-01	Results First Posted N/A	Last Verified 2021-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: HIPEC Immediately following laparoscopy for diagnosis and staging of disease, closed neoadjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) will be performed using the anatomical site of the laparoscopic procedure in the same operative encounter. Perfusi	PROCEDURE: Hyperthermic intraperitoneal chemotherapy HIPEC in this study involves the washing of the peritoneal cavity with a heated (40-48°C), (1000 mg/m sq) solution of gemcitabine in 1.5% dextrose for 90 min. Compared with systemic delivery of chemotherapy, intraperitoneal delivery can increase site-spec PROCEDURE: Open pancreaticoduodenectomy Tumors of the pancreatic head will be surgically removed by open PD (standard and pylorus-preserving approaches) with the aim of achieving en bloc R0 tumor resection (no macroscopic residual cancer remaining). In all patients, a lymphadenectomy will be pe DRUG: Gemcitabine Neoadjuvant and adjuvant systemic chemotherapy will be administered to all PDAC patients with the aim of diminishing the tumor burden and maximizing the chance of complete surgical resection. Gemcitabine (GEMZAR®) will be administered for 6 months (includ
OTHER: Historical Control Case-matched historical controls will have received neoadjuvant chemotherapy with gemcitabine prior to open pancreaticoduodenectomy (PD) by the standard Whipple or pylorus-preserving approach. Adjuvant systemic chemotherapy (SCT) with gemcitabine will be	PROCEDURE: Open pancreaticoduodenectomy Tumors of the pancreatic head will be surgically removed by open PD (standard and pylorus-preserving approaches) with the aim of achieving en bloc R0 tumor resection (no macroscopic residual cancer remaining). In all patients, a lymphadenectomy will be pe DRUG: Gemcitabine Neoadjuvant and adjuvant systemic chemotherapy will be administered to all PDAC patients with the aim of diminishing the tumor burden and maximizing the chance of complete surgical resection. Gemcitabine (GEMZAR®) will be administered for 6 months (includ

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: HIPEC

Immediately following laparoscopy for diagnosis and staging of disease, closed neoadjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) will be performed using the anatomical site of the laparoscopic procedure in the same operative encounter. Perfusi

PROCEDURE: Hyperthermic intraperitoneal chemotherapy

HIPEC in this study involves the washing of the peritoneal cavity with a heated (40-48°C), (1000 mg/m sq) solution of gemcitabine in 1.5% dextrose for 90 min. Compared with systemic delivery of chemotherapy, intraperitoneal delivery can increase site-spec

PROCEDURE: Open pancreaticoduodenectomy

Tumors of the pancreatic head will be surgically removed by open PD (standard and pylorus-preserving approaches) with the aim of achieving en bloc R0 tumor resection (no macroscopic residual cancer remaining). In all patients, a lymphadenectomy will be pe

DRUG: Gemcitabine

Neoadjuvant and adjuvant systemic chemotherapy will be administered to all PDAC patients with the aim of diminishing the tumor burden and maximizing the chance of complete surgical resection. Gemcitabine (GEMZAR®) will be administered for 6 months (includ

OTHER: Historical Control

Case-matched historical controls will have received neoadjuvant chemotherapy with gemcitabine prior to open pancreaticoduodenectomy (PD) by the standard Whipple or pylorus-preserving approach. Adjuvant systemic chemotherapy (SCT) with gemcitabine will be

PROCEDURE: Open pancreaticoduodenectomy

Tumors of the pancreatic head will be surgically removed by open PD (standard and pylorus-preserving approaches) with the aim of achieving en bloc R0 tumor resection (no macroscopic residual cancer remaining). In all patients, a lymphadenectomy will be pe

DRUG: Gemcitabine

Neoadjuvant and adjuvant systemic chemotherapy will be administered to all PDAC patients with the aim of diminishing the tumor burden and maximizing the chance of complete surgical resection. Gemcitabine (GEMZAR®) will be administered for 6 months (includ

Primary Outcome Measures	Measure Description	Time Frame
Peritoneal disease-free survival	Peritoneal disease-free survival is defined as the time between staging laparoscopy confirming no peritoneal disease (at the time of HIPEC treatment) and regional recurrence of pancreatic ductal adenocarcinoma on the peritoneal surfaces as determined by diagnostic imaging. This definition is exclusive of recurrence status in the pancreatic remnant after resection.	2 years

Secondary Outcome Measures	Measure Description	Time Frame
Overall survival		1, 2, 3, 5 years
Local disease-free survival	Local disease-free survival is defined as the time between staging laparoscopy (at the time of HIPEC treatment) and local recurrence of pancreatic ductal adenocarcinoma in the pancreatic remnant as determined by diagnostic imaging.	2 years
Postoperative morbidity		1 and 3 months
Postoperative mortality		1 and 3 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Primary diagnosis of pancreatic ductal adenocarcinoma (PDAC) confined to the head of the pancreas classified as T1-T3 with one or more of the following high-risk clinical features:

Carbohydrate antigen (CA) 19-9 greater than 1,000 U/mL with a normal bilirubin;
Vascular involvement; and/or
Suspicious regional lymphadenopathy
Intention to undergo open pancreaticoduodenectomy (standard Whipple or pylorus-preserving pancreaticoduodenectomy) as treatment for PDAC
Adequate clinical condition to undergo preoperative (neoadjuvant) hyperthermic intraperitoneal chemotherapy
Adequate clinical condition to undergo perioperative systemic chemotherapy
White blood cell count of at least 3000/mL
Platelet count of at least 100,000/mL
Normal creatinine (< 2 mg/dL) or creatinine clearance of at least 50 mL/min
Willing and able to give informed consent

Evidence of locoregional spread (carcinomatosis of peritoneal surfaces, mesenteric arteries, or body/tail of pancreas) or distant (liver, lung, or other) metastases (histological, CT, or MRI confirmation)
Non-curative intent of treatment (≥R2 resection)
Body mass index (BMI) > 35
Previous history of pancreatic resections for tumors in the body and/or tail of the pancreas, distal cholangiocarcinoma, duodenal carcinoma, neuroendocrine tumors, cyst-adenocarcinoma, or solid and papillary tumors.
Unstable or uncompensated respiratory or cardiac disease
Severe hepatic or renal dysfunction
Bleeding diathesis or coagulopathy
Pregnant or nursing women

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Dionisios Vrochides, MD PhD FACS, Carolinas Medical Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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