Acinar Cell Carcinoma, Ampulla of Vater Adenocarcinoma, Cholangiocarcinoma, Duodenal Adenocarcinoma, Pancreatic Adenocarcinoma, Pancreatic Ductal Adenocarcinoma, Pancreatic Intraductal Papillary Mucinous Neoplasm, Periampullary Adenocarcinoma
Conditions
Brief summary
The goal of this clinical trial is to learn if a special washing treatment used during surgery can help people with pancreatic cancer live longer. The study includes adults who are having surgery for suspected pancreatic cancer or related cancers in nearby organs (called periampullary cancers). The main questions it aims to answer are: * Does the washing treatment improve overall survival (how long patients live)? * Does it improve how long patients remain cancer-free and reduce cancer recurrence or complications? The investigators will compare two types of washing treatments and standard care to see if either method improves outcomes. Participants will: Be assigned by chance (randomized) before surgery to one of three groups: * Washing with warm saltwater (saline) * Washing with sterile water * No extensive washing (standard care) Undergo their planned cancer surgery, during which the washing treatment (if assigned) will be performed right after the tumor is removed Be followed over time to monitor survival, cancer recurrence, and any side effects The investigators estimate the washing treatment could increase average survival from about 18 months to 27 months. To ensure enough patients with confirmed pancreatic cancer are included, about 845 participants will be enrolled over time.
Detailed description
PRIMARY OBJECTIVE: To compare overall survival (OS) following pancreatic resection between subjects receiving extensive abdominal lavage with saline (EAL-S), extensive abdominal lavage with distilled water (EAL-W), and standard of care without extensive lavage. SECONDARY OBJECTIVES: I. Disease-free survival (DFS). II. Complication rate. III. Site of first recurrence (by site and distant versus local recurrence). IV. Clearance of malignant cells pre- versus post-lavage. STUDY DESIGN: This is a prospective, randomized, participant-blinded clinical trial evaluating extensive abdominal lavage during pancreatic resection for pancreatic and periampullary malignancies. Subjects are enrolled preoperatively and randomized prior to entering the operating room. Randomization is stratified by study site and use of neoadjuvant therapy. Subjects are randomized to one of three treatment arms: Arm I (EAL-S): Subjects undergo pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy followed immediately after specimen removal by extensive abdominal lavage using 10 liters of warmed 0.9% normal saline administered as ten sequential 1-liter irrigations with aspiration. Arm II (EAL-W): Subjects undergo pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy followed immediately after specimen removal by extensive abdominal lavage using 10 liters of warmed distilled water administered as ten sequential 1-liter irrigations with aspiration. Arm III (Standard of Care/No Extensive Lavage): Subjects undergo pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy without protocol-directed extensive lavage following specimen removal. The extensive lavage procedure is performed immediately after specimen removal and generally requires approximately 15 minutes. A total of 845 subjects were enrolled. Subjects with suspected pancreatic or periampullary malignancy are enrolled preoperatively because definitive diagnosis cannot be established before resection. The primary efficacy analysis population consists of subjects with resected pancreatic cancer according to protocol-defined criteria. For approximately the first 200 enrolled subjects, cytologic washings are obtained at predefined intraoperative time points (pre-dissection, post-resection, post-lavage, and specimen washing) for correlative analyses evaluating malignant cell clearance. Additional biologic studies may be performed using collected specimens. Following completion of study treatment, subjects are followed initially at approximately 30 days after surgery and then every 3 months thereafter for survival, recurrence, postoperative outcomes, and adjuvant treatment information for up to 5 years following surgery or until death, whichever occurs first.
Interventions
PROCEDUREPancreatectomy
Undergo pancreaticoduodenectomy, distal pancreatectomy, or total pancreatectomy
OTHERLavage
Receive EAL-S
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The subject has a surgical indication for pancreatectomy (pancreaticoduodenctomy, distal pancreatectomy, total pancreatectomy) as determined by the treating physician/surgeon * A diagnosis of pancreatic or other periampullary cancer is suspected preoperatively * In the opinion of the surgeon, the subject has no medical contraindications to pancreatectomy * Age ≥18 years of age. * The subject is willing to consent to randomization of EAL-S vs. EAL-W vs. no extensive lavage (SOC)
Exclusion criteria
* The subject does not have a surgical indication for pancreatectomy * In the opinion of the surgeon, the subject has medical contraindications to pancreatectomy * Age \<18 years of age * The subject is not willing to consent to EAL-S vs. EAL-W vs. no extensive lavage (SOC) * Known benign or indolent disease (including benign pancreatic cystic tumors or pancreatic endocrine tumors) without possible risk of malignancy * Other malignancy within five years, unless the probability of recurrence of the prior malignancy is \<5% as determined by the Principal Investigator based on available information. Patient's curatively treated for squamous and basal cell carcinoma of the skin or patients with a history of malignant tumor in the past that have been disease free for at least five years are also eligible for this study. * Evidence of metastatic disease preoperatively
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 27 months after resection | Will use a one-sided log-rank test to separately compare lavage (EAL-S or EAL-W) to no lavage with respect to OS. Assuming the study is not stopped at the interim analyses, the final comparison will be made with an alpha level of 0.02493. Distribution of OS will be estimated using the Kaplan-Meier method. Secondary analyses will use Cox regression to adjust the lavage/no lavage comparison for other baseline patient and/or characteristics known to be associated with OS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of overall complications and specific complications graded in severity using Common Terminology Criteria for Adverse Events (v4.0) | Up to 5 years after resection | Will use chi-square or Fisher's exact test for dichotomous outcomes and Poisson regression for count outcomes. |
| Disease Free survival (DFS) | Up to 5 years after resection | Will use log-rank tests for time-to-event outcomes. |
| Site of first recurrence (by site, distant vs local) | Up to 5 years after resection | First recurrence site will be categorized by anatomic site and as local versus distant recurrence. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORHarish Lavu, MD
Thomas Jefferson University
Outcome results
None listed