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

• Sponsor: University of California, San Diego (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03352414
• Collaborator: (none)
• Enrollment: 84
• Location: 1
• Arms: 2
• Actual Duration (Months): 25.7
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Ileus	Drug: Alvimopan; Drug: Placebo	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The ILEUS Study: A Phase 2 Randomized Controlled Trial Investigating Alvimopan for Enhanced Gastrointestinal Recovery After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
• Actual Study Start Date: Mar 8, 2018
• Actual Primary Completion Date: Apr 28, 2020
• Actual Study Completion Date: Apr 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alvimopan alvimopan 12 mg PO twice daily, starting POD 1 for the earlier of 7 days or hospital discharge	Drug: Alvimopan; alvimopan pill; Other Names: Entereg
Placebo Comparator: Placebo Placebo pill PO twice daily, starting POD 1 for the earlier of 7 days or hospital discharge	Drug: Placebo; placebo pill; Other Names: Placebi

Outcome Measures

Primary Outcome Measures

1. Time to Return of Upper and Lower GI Function [from surgery to discharge (generally no longer than two weeks)]

   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.

Secondary Outcome Measures

1. Prolonged Ileus [from surgery to discharge (generally no longer than two weeks)]

   The proportion of patients who do not pass flatus or bowel movement greater than 7 days from the time of surgery.

2. Time to Return of Bowel Function Components [from surgery to discharge (generally no longer than two weeks)]

   The time from surgery until: The time to first flatus The time to first bowel movement The time to tolerance of solid food

3. Time to Discharge [from surgery to discharge (generally no longer than two weeks)]

   The time from surgery until discharge order written.

4. Serious Adverse Events [up to 30 days from surgery]

   The number and proportion of serious adverse events.

5. Subgroup Analyses [up to 30 days from surgery]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSD Moores Cancer Center	La Jolla	California	United States	92093-0987

Sponsors and Collaborators

• University of California, San Diego

Investigators

• Principal Investigator: Joel M Baumgartner, MD, MAS, UCSD

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 25, 2019

More Information

Publications

None provided.

• Responsible Party: Joel Baumgartner, Assistant Professor of Surgery, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT03352414
• Other Study ID Numbers: 171044
• First Posted: Nov 24, 2017
• Last Update Posted: Aug 18, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Joel Baumgartner, Assistant Professor of Surgery, University of California, San Diego: HIPEC; peritoneal carcinomatosis
• Additional relevant MeSH terms: Ileus; Alvimopan

Study Results

Participant Flow

Pre-assignment Detail	84 participants were enrolled and randomized (constitute the safety population). All participants must later meet surgical eligibility for final allocation and analysis (n=62).

Arm/Group Title	Alvimopan	Placebo
Arm/Group Description	Alvimopan: alvimopan pill	Placebo: placebo pill
Period Title: Overall Study
STARTED	42	42
Allocated	30	32
COMPLETED	30	32
NOT COMPLETED	12	10

Baseline Characteristics

Arm/Group Title	Alvimopan	Placebo	Total
Arm/Group Description	Alvimpan Arm	Placebo Arm	Total of all reporting groups
Overall Participants	30	32	62
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53	61	57
Sex: Female, Male (Count of Participants)
Female	22 73.3%	12 37.5%	34 54.8%
Male	8 26.7%	20 62.5%	28 45.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Time to Return of Upper and Lower GI Function
Description	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.
Time Frame	from surgery to discharge (generally no longer than two weeks)

Outcome Measure Data

Analysis Population Description

Study was terminated early, preliminary data

Arm/Group Title	Alvimopan	Placebo
Arm/Group Description	Alvimopan: alvimopan pill	Placebo: placebo pill
Measure Participants	30	32
Median (95% Confidence Interval) [hours]	117	152

2. Secondary Outcome

Title	Prolonged Ileus
Description	The proportion of patients who do not pass flatus or bowel movement greater than 7 days from the time of surgery.
Time Frame	from surgery to discharge (generally no longer than two weeks)

Outcome Measure Data

Analysis Population Description

Study was terminated early, preliminary data

Arm/Group Title	Alvimopan	Placebo
Arm/Group Description	Alvimopan: alvimopan pill	Placebo: placebo pill
Measure Participants	30	32
Count of Participants [Participants]	3 10%	12 37.5%

3. Secondary Outcome

Title	Time to Return of Bowel Function Components
Description	The time from surgery until: The time to first flatus The time to first bowel movement The time to tolerance of solid food
Time Frame	from surgery to discharge (generally no longer than two weeks)

Outcome Measure Data

Analysis Population Description

Study was terminated early, preliminary data

Arm/Group Title	Alvimopan	Placebo
Arm/Group Description	Alvimopan: alvimopan pill	Placebo: placebo pill
Measure Participants	30	32
Time to first flatus	64	79
Time to first BM	67	89
Time to tolerance of solid food	117	149

4. Secondary Outcome

Title	Time to Discharge
Description	The time from surgery until discharge order written.
Time Frame	from surgery to discharge (generally no longer than two weeks)

Outcome Measure Data

Analysis Population Description

Study was terminated early, preliminary data

Arm/Group Title	Alvimopan	Placebo
Arm/Group Description	Alvimpan Arm	Placebo Arm
Measure Participants	30	32
Median (95% Confidence Interval) [hours]	188	190

5. Secondary Outcome

Title	Serious Adverse Events
Description	The number and proportion of serious adverse events.
Time Frame	up to 30 days from surgery

Outcome Measure Data

Analysis Population Description

From Safety population (n=84) Study was terminated early, preliminary data

Arm/Group Title	Alvimopan	Placebo
Arm/Group Description	Alvimopan: alvimopan pill	Placebo: placebo pill
Measure Participants	42	42
Count of Participants [Participants]	7 23.3%	5 15.6%

6. Secondary Outcome

Title	Subgroup Analyses
Description	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
Time Frame	up to 30 days from surgery

Outcome Measure Data

Analysis Population Description

Study was terminated early, data was not collected.

Arm/Group Title	Alvimopan	Placebo
Arm/Group Description	Alvimopan: alvimopan pill	Placebo: placebo pill
Measure Participants	0	0

Adverse Events

Time Frame	30 days from the the time of surgery
Adverse Event Reporting Description	CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.
Arm/Group Title	Alvimopan		Placebo
Arm/Group Description	Alvimopan: alvimopan pill		Placebo: placebo pill
All Cause Mortality
	Alvimopan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0%)		0/42 (0%)
Serious Adverse Events
	Alvimopan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/42 (16.7%)		5/42 (11.9%)
Blood and lymphatic system disorders
Thromboembolic Event	0/42 (0%)	0	1/42 (2.4%)	1
Cardiac disorders
Cardiac Arrest	0/42 (0%)	0	1/42 (2.4%)	1
Gastrointestinal disorders
Abdominal Pain	4/42 (9.5%)	4	0/42 (0%)	0
Rectal Perforation	1/42 (2.4%)	1	0/42 (0%)	0
Constipation	1/42 (2.4%)	1	0/42 (0%)	0
Gastric Perforation	0/42 (0%)	0	1/42 (2.4%)	1
Metabolism and nutrition disorders
Dehydration	0/42 (0%)	0	1/42 (2.4%)	1
Renal and urinary disorders
Acute Kidney Injury	1/42 (2.4%)	1	0/42 (0%)	0
Surgical and medical procedures
Wound Dehiscence	0/42 (0%)	0	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Alvimopan		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/42 (83.3%)		37/42 (88.1%)
Surgical and medical procedures
Non-Serious Adverse Events	35/42 (83.3%)	35	37/42 (88.1%)	37

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.