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HIPEC as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma

Primary Purpose

Pancreatic Neoplasms, Pancreatic Adenocarcinoma

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hyperthermic intraperitoneal chemotherapy
Open pancreaticoduodenectomy
Gemcitabine
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Neoplasms focused on measuring hyperthermic intraperitoneal chemotherapy, perioperative systemic chemotherapy, peritoneal disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Carolinas Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

HIPEC

Historical Control

Arm Description

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. Perfusion will be initiated with 4-6 L of 1.5% dextrose at a 500 mL/min flow rate with manual agitation of the abdominal wall. Once the temperature in the abdomen becomes stable above 40°C, perfusate volume will be reduced to 1.5 L/m sq, and gemcitabine (GEMZAR®) will be instilled into the abdomen (1000 mg/m sq) for 90 min. Neoadjuvant chemotherapy with gemcitabine will be administered prior to open pancreaticoduodenectomy by the standard Whipple or pylorus-preserving approach. Adjuvant systemic chemotherapy with gemcitabine will be administered for 6 months (including period of neoadjuvant therapy) according to established institutional protocol.

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 administered for 6 mo (including period of neoadjuvant therapy) according to established institutional protocol.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Overall survival
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.
Postoperative morbidity
Postoperative mortality

Full Information

First Posted
July 25, 2016
Last Updated
April 20, 2022
Sponsor
Wake Forest University Health Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02850874
Brief Title
HIPEC as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma
Official Title
Hyperthermic Intraperitoneal Chemotherapy as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma: A Prospective, Phase II, Proof-of-concept Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Withdrawn
Why Stopped
no accrual rate
Study Start Date
February 2016 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Neoplasms, Pancreatic Adenocarcinoma
Keywords
hyperthermic intraperitoneal chemotherapy, perioperative systemic chemotherapy, peritoneal disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HIPEC
Arm Type
Experimental
Arm Description
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. Perfusion will be initiated with 4-6 L of 1.5% dextrose at a 500 mL/min flow rate with manual agitation of the abdominal wall. Once the temperature in the abdomen becomes stable above 40°C, perfusate volume will be reduced to 1.5 L/m sq, and gemcitabine (GEMZAR®) will be instilled into the abdomen (1000 mg/m sq) for 90 min. Neoadjuvant chemotherapy with gemcitabine will be administered prior to open pancreaticoduodenectomy by the standard Whipple or pylorus-preserving approach. Adjuvant systemic chemotherapy with gemcitabine will be administered for 6 months (including period of neoadjuvant therapy) according to established institutional protocol.
Arm Title
Historical Control
Arm Type
Other
Arm Description
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 administered for 6 mo (including period of neoadjuvant therapy) according to established institutional protocol.
Intervention Type
Procedure
Intervention Name(s)
Hyperthermic intraperitoneal chemotherapy
Other Intervention Name(s)
HIPEC
Intervention Description
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-specific concentration of chemotherapeutic agents and decrease duration of perfusion, vascular complications, and systemic toxicity. The use of heated chemotherapeutic agents, compared to conventional protocols, has been shown to increase direct cytotoxicity to malignant cells and augment penetration into tumors.
Intervention Type
Procedure
Intervention Name(s)
Open pancreaticoduodenectomy
Other Intervention Name(s)
Whipple procedure, Pylorus-preserving pancreaticoduodenectomy (PPPD)
Intervention Description
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 performed along the hepatoduodenal ligament, common hepatic artery, vena cava, and the interaortocaval and right side of the superior mesenteric artery. In cases with portal vein involvement, a venous resection will be performed to achieve R0 resection. Patients with arterial infiltration by the tumor will be deemed locally nonresectable and will be excluded from analysis. Established, routine surgical and ERAS protocols will be followed for pre-, intra-, and postoperative care of patients. Patients will be discharged after postoperative day 5 if tolerating oral intake and showing no signs or symptoms of complications.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
GEMZAR®
Intervention Description
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 (including period of neoadjuvant therapy) according to established institutional guidelines for dosing, frequency, duration, administration route, and setting.
Primary Outcome Measure Information:
Title
Peritoneal disease-free survival
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
1, 2, 3, 5 years
Title
Local disease-free survival
Description
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.
Time Frame
2 years
Title
Postoperative morbidity
Time Frame
1 and 3 months
Title
Postoperative mortality
Time Frame
1 and 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dionisios Vrochides, MD PhD FACS
Organizational Affiliation
Carolinas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Carolinas Medical Center
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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HIPEC as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma

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