Clinical trial NCT01004393: Methylnaltrexone for Opioid-induced Constipation in Cancer Patients
Official title: Phase II Trial of Subcutaneous Methylnaltrexone in the Treatment of Severe Opioid-induced Constipation in Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms
Constipation
Opioid-Related Disorders
Keywords: Methylnaltrexone
Constipation
Narcotic Antagonists
Analgesics, Opioid
Neoplasms
Lead sponsor: University of Vermont
Sponsor class: OTHER
First posted: 2009-10-29
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to evaluate the efficacy of methylnaltrexone in relieving opioid-induced constipation in cancer patients at various stages of disease.

Detailed description: Pain is one of the most common and important symptoms of cancer, often requiring opioid analgesics for control. However constipation is one of the most frequent and debilitating side effects of opioids, occurring in 40%-70% of patients being treated for chronic pain. Although laxatives are commonly used to manage opioid-induced constipation, these agents are not always effective or satisfactory. Methylnaltrexone bromide is a peripherally acting antagonist of the mu-opioid receptor. As a quaternary amine, the ability of methylnaltrexone to cross the blood-brain barrier is limited. This allows methylnaltrexone to function as a peripherally-acting antagonist in the gastrointestinal tract without impacting opioid-mediated analgesic effects in the central nervous system. The efficacy and safety of methylnaltrexone in treating opioid-induced constipation in patients with advanced disease receiving palliative care has been demonstrated. However the efficacy of this agent has not been evaluated in more active patients who are earlier in their disease course. The present study will evaluate the efficacy and safety of methylnaltrexone for the relief of severe opioid-induced constipation in this population and will attempt to identify factors predictive of methylnaltrexone response.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed neoplasm
* 18 years of age or older
* Have received opioids for analgesia for at least 2 weeks and been on a stable regimen of opioids and laxatives for 3 or more days before study entry
* Fewer than three laxation during the preceding week and no laxation within 24 hours before study entry, or no laxation within 48 hours before study entry
* Life expectancy of at least 6 months
* World Health Organization Performance Status 0-3
* Women of childbearing potential must have a negative pregnancy test
* Breastfeeding should be discontinued prior to study entry
* Ability to understand and the willingness to sign a written informed consent document.
* Laboratory values within a week of study entry:

Absolute neutrophil count \> 1,500/microliter Hemoglobin \> 7 g/dL Platelet count \> 100,000/microliter Calculated calcium \< 10.5 mg/dL Calculated creatinine clearance \> 30 mg.min Alanine aminotransferase \< 3 x upper limit of normal (ULN) Aspartate aminotransferase \< 3 x ULN Alkaline phosphatase \< 2.5 x ULN Bilirubin \< 1.5 x ULN

Exclusion Criteria:

* Constipation not primarily caused by opioids, such as mechanical gastrointestinal obstruction or ongoing vinca alkaloid administration
* Indwelling peritoneal catheter
* Clinically active diverticular disease
* Fecal impaction
* Acute surgical abdomen
* Fecal ostomy
* Peritoneal carcinomatosis
* Known hypersensitivity to methylnaltrexone, naltrexone, or naloxone
* Administration of any investigational drug or experimental product within the previous 30 days
* Initiation of a new bowel regimen or prokinetic agents within a week of study entry

Primary outcomes:
measure: Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone
timeFrame: 4 hours after the dose of subcutaneous methylnaltrexone
Secondary outcomes:
measure: Laxation After Administration of Subcutaneous Methylnaltrexone
timeFrame: 24 and 48 hours after the dose of subcutaneous methylnaltrexone
measure: Time to Laxation After Administration of Subcutaneous Methylnaltrexone
timeFrame: 48 hours after the dose of subcutaneous methylnaltrexone
measure: Overall Pain Scores (0-10; 0=no Pain, 10=Worst Pain) After Administration of Subcutaneous Methylnaltrexone
timeFrame: 48 hours after the dose of subcutaneous methylnaltrexone
measure: Symptoms of Opioid Withdrawal (Modified Himmelsbach Withdrawal Scales (Ranging 7-28 in Total; 1=None - 4=Severe for 7 Items)) After Administration of Subcutaneous Methylnaltrexone
timeFrame: 48 hours after the dose of subcutaneous methylnaltrexone
measure: Bowel Movement Assessment (Frequency, Consistency and Difficulty) After Administration of Subcutaneous Methylnaltrexone
timeFrame: 48 hours after the dose of subcutaneous methylnaltrexone
measure: Constipation Assessment (Severity and Distress) After Administration of Subcutaneous Methylnaltrexone
timeFrame: 48 hours after the dose of subcutaneous methylnaltrexone
measure: Patient Satisfaction With the Study Medication After Administration of Subcutaneous Methylnaltrexone
timeFrame: 48 hours after the dose of subcutaneous methylnaltrexone
Other outcomes:
Locations:
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
Study officials:
affiliation: Fletcher Allen Health Care / University of Vermont College of Medicine
name: Steven Ades, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mori M, Ji Y, Kumar S, Ashikaga T, Ades S. Phase II trial of subcutaneous methylnaltrexone in the treatment of severe opioid-induced constipation (OIC) in cancer patients: an exploratory study. Int J Clin Oncol. 2017 Apr;22(2):397-404. doi: 10.1007/s10147-016-1041-6. Epub 2016 Sep 15.