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Phase II Trial of Subcutaneous Methylnaltrexone in the Treatment of Severe Opioid-induced Constipation in Cancer Patients

Phase 2
18 Years
Open (Enrolling)
Neoplasms, Constipation, Opioid-Related Disorders

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Trial Information

Phase II Trial of Subcutaneous Methylnaltrexone in the Treatment of Severe Opioid-induced Constipation in Cancer Patients

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.

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 laxations 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

- WHO 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Outcome Measure:

Rescue-free laxation after administration of subcutaneous methylnaltrexone

Outcome Time Frame:

4 hours after the dose of subcutaneous methylnaltrexone

Safety Issue:


Principal Investigator

Steven M Grunberg, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fletcher Allen Health Care / University of Vermont College of Medicine


United States: Institutional Review Board

Study ID:

VCC 0911



Start Date:

October 2009

Completion Date:

January 2013

Related Keywords:

  • Neoplasms
  • Constipation
  • Opioid-Related Disorders
  • Methylnaltrexone
  • Constipation
  • Narcotic Antagonists
  • Analgesics, Opioid
  • Neoplasms
  • Neoplasms
  • Constipation
  • Opioid-Related Disorders



Fletcher Allen Health CareBurlington, Vermont  05401