HIPEC as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma

Pancreatic Neoplasms Clinical Trial

Official title:

Hyperthermic Intraperitoneal Chemotherapy as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma: A Prospective, Phase II, Proof-of-concept Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02850874
• Other study ID #: 02-16-05A
• Status: Withdrawn
• Phase: Phase 2
• Start date: February 2016
• Est. completion date: December 2016

Study information

• Verified date: January 2021
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Adenocarcinoma
• Pancreatic Neoplasms

Intervention

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-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.
• 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 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.

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 (including period of neoadjuvant therapy) according to established institutional guidelines for dosing, frequency, duration, administration route, and setting.

Locations

Country	Name	City	State
United States	Carolinas Medical Center	Charlotte	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival		1, 2, 3, 5 years
Secondary	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
Secondary	Postoperative morbidity		1 and 3 months
Secondary	Postoperative mortality		1 and 3 months