Phase 2 RCT of Alvimopan vs. Placebo After CRS/HIPEC

Study Overview
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Brief Summary
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The purpose of this study is to investigate the ability of alvimopan to reduce the time to return of bowel function in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Half of the participants will receive alvimopan or and half will receive placebo immediately before and for up to seven days after surgery.

Detailed Description
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Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a surgical procedure to treat cancer that has spread to the lining of the abdominal cavity (peritoneal metastases). It is associated with a prolonged time for return of bowel function after surgery. Alvimopan is a drug used to speed up the time for return of bowel function after surgery. It works by blocking the opioid receptors in the gastrointestinal tract, which normally slow down bowel function in patients receiving postoperative opioid pain medication. It has not previously been tested in patients undergoing CRS/HIPEC.

Official Title
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The ILEUS Study: A Phase 2 Randomized Controlled Trial Investigating Alvimopan for Enhanced Gastrointestinal Recovery After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Conditions
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Ileus

Intervention / Treatment
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* Drug: Alvimopan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent. Scheduled to undergo open (non-minimally invasive) CRS/HIPEC. Scheduled to receive postoperative pain management with intravenous opioids. Age > 18 years. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2. Women of child-bearing potential with negative pregnancy test prior to initiating study drug dosing. Exclusion Criteria: Greater than 7 days of consecutive opioid use immediately prior to scheduled surgery. Child-Pugh Class C hepatic impairment. End-stage renal disease (GFR < 15 mL/min/1.73 m2 and/or on peritoneal dialysis or hemodialysis). Complete mechanical bowel obstruction. Contraindication or inability to tolerate oral medication postoperatively. Presence of gastrointestinal ostomy after CRS/HIPEC. Pancreatic or gastric anastomosis performed during CRS/HIPEC. History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition as alvimopan at the treating investigators discretion. Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study treatment (i.e. uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements). History of myocardial infarction in the 12 months prior to scheduled surgery. Pregnant or nursing.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alvimopan<br>alvimopan 12 mg PO twice daily, starting POD 1 for the earlier of 7 days or hospital discharge | Drug: Alvimopan<br>* alvimopan pill<br>* Other names: Entereg;|
| Placebo Comparator: Placebo<br>Placebo pill PO twice daily, starting POD 1 for the earlier of 7 days or hospital discharge | Drug: Placebo<br>* placebo pill<br>* Other names: Placebi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Return of Upper and Lower GI Function | The later of the time from surgery that the participant first tolerates solid food and the time that the participant first passes a bowel movement. | from surgery to discharge (generally no longer than two weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prolonged Ileus | The proportion of patients who do not pass flatus or bowel movement greater than 7 days from the time of surgery. | from surgery to discharge (generally no longer than two weeks) | 
| Time to Return of Bowel Function Components | The time from surgery until: The time to first flatus The time to first bowel movement The time to tolerance of solid food | from surgery to discharge (generally no longer than two weeks) | 
| Time to Discharge | The time from surgery until discharge order written. | from surgery to discharge (generally no longer than two weeks) | 
| Serious Adverse Events | The number and proportion of serious adverse events. | up to 30 days from surgery | 
| Subgroup Analyses | All primary and secondary outcomes will be measured in the following subgroups: 0 vs. 1 or greater bowel anastomoses 0 vs. 1 or greater visceral resections high vs. low amount of postoperative opioid use epidural vs. no epidural | up to 30 days from surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIPEC, peritoneal carcinomatosis