NCT02850874

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Feb 2016

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2016

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

July 25, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

August 1, 2016

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

April 27, 2022

Status Verified

January 1, 2021

Enrollment Period

10 months

First QC Date

July 25, 2016

Last Update Submit

April 20, 2022

Conditions

Pancreatic NeoplasmsPancreatic Adenocarcinoma

Keywords

hyperthermic intraperitoneal chemotherapyperioperative systemic chemotherapyperitoneal disease

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (4)

  • Overall survival

    1, 2, 3, 5 years

  • Local disease-free survival

    2 years

  • Postoperative morbidity

    1 and 3 months

  • Postoperative mortality

    1 and 3 months

Study Arms (2)

HIPEC

EXPERIMENTAL

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.

Procedure: Hyperthermic intraperitoneal chemotherapyProcedure: Open pancreaticoduodenectomyDrug: Gemcitabine

Historical Control

OTHER

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.

Procedure: Open pancreaticoduodenectomyDrug: Gemcitabine

Interventions

Hyperthermic intraperitoneal chemotherapyPROCEDURE

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.

Also known as: HIPEC
HIPEC
Open pancreaticoduodenectomyPROCEDURE

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.

Also known as: Whipple procedure, Pylorus-preserving pancreaticoduodenectomy (PPPD)
HIPECHistorical Control
GemcitabineDRUG

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.

Also known as: GEMZAR®
HIPECHistorical Control

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Carolinas Medical Center

Charlotte, North Carolina, 28204, United States

Location

MeSH Terms

Conditions

Pancreatic NeoplasmsPeritoneal Diseases

Interventions

Hyperthermic Intraperitoneal ChemotherapyPancreaticoduodenectomyGemcitabine

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Chemotherapy, AdjuvantCombined Modality TherapyTherapeuticsDrug TherapyHyperthermia, InducedDigestive System Surgical ProceduresSurgical Procedures, OperativeHeterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Dionisios Vrochides, MD PhD FACS

    Carolinas Medical Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 25, 2016

First Posted

August 1, 2016

Study Start

February 1, 2016

Primary Completion

December 1, 2016

Study Completion

December 1, 2016

Last Updated

April 27, 2022

Record last verified: 2021-01

Locations

US(1)