- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02850874
HIPEC as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma
Hyperthermic Intraperitoneal Chemotherapy as Neoadjuvant Treatment for Resectable Pancreatic Adenocarcinoma: A Prospective, Phase II, Proof-of-concept Study
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Carolinas Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
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.
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.
|
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.
Other Names:
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.
Other Names:
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.
Other Names:
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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 administered for 6 mo (including period of neoadjuvant therapy) according to established institutional protocol.
|
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.
Other Names:
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Peritoneal disease-free survival
Time Frame: 2 years
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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.
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2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 1, 2, 3, 5 years
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1, 2, 3, 5 years
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Local disease-free survival
Time Frame: 2 years
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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.
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2 years
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Postoperative morbidity
Time Frame: 1 and 3 months
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1 and 3 months
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Postoperative mortality
Time Frame: 1 and 3 months
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1 and 3 months
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Collaborators and Investigators
Investigators
- Principal Investigator: Dionisios Vrochides, MD PhD FACS, Carolinas Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Adenocarcinoma
- Pancreatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Gemcitabine
Other Study ID Numbers
- 02-16-05A
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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