HIPEC as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma

Wake Forest University (WFU)

Status and phase: Withdrawn; Phase 2

Conditions: Pancreatic Adenocarcinoma; Pancreatic Neoplasms

Treatments: Drug: Gemcitabine; Procedure: Hyperthermic intraperitoneal chemotherapy; Procedure: Open pancreaticoduodenectomy

Study type: Interventional

Funder types: Other

Identifiers

NCT02850874

02-16-05A

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

HIPEC

Experimental group

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.

Treatment:

Procedure: Open pancreaticoduodenectomy

Procedure: Hyperthermic intraperitoneal chemotherapy

Drug: Gemcitabine

Historical Control

Other group

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.

Treatment:

Procedure: Open pancreaticoduodenectomy

Drug: Gemcitabine