Methylnaltrexone for Opioid-induced Constipation in Cancer Patients

NCT ID: NCT01004393

Last Updated: 2016-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2013-12-31

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.

Conditions

Neoplasms; Constipation; Opioid-Related Disorders

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Methylnaltrexone bromide

A single dose of methylnaltrexone will be administered subcutaneously to eligible subjects based on weight at the study entry. Since we will include subjects at all stages of cancer management, administering this study drug is considered experimental. We will use the dose approved by FDA, i.e., 0.15 mg/kg (round dose up to nearest 0.1 mL of volume) for weight less than 38 kg or greater than 114 kg; 8 mg (0.4 mL) for weight 38 kg to less than 62 kg; and 12 mg (0.6 mL) for weight 62 kg to 114 kg.

Group Type: EXPERIMENTAL

Methylnaltrexone bromide

Intervention Type: DRUG

Methylnaltrexone bromide, dosage based on weight (0.15 mg/kg (round dose up to nearest 0.1 mL of volume) for weight less than 38 kg or greater than 114 kg; 8 mg (0.4 mL) for weight 38 kg to less than 62 kg; and 12 mg (0.6 mL) for weight 62 kg to 114 kg), single dose

Interventions

Methylnaltrexone bromide

Methylnaltrexone bromide, dosage based on weight (0.15 mg/kg (round dose up to nearest 0.1 mL of volume) for weight less than 38 kg or greater than 114 kg; 8 mg (0.4 mL) for weight 38 kg to less than 62 kg; and 12 mg (0.6 mL) for weight 62 kg to 114 kg), single dose

Intervention Type: DRUG

Other Intervention Names

Relistor

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Vermont

OTHER

Sponsor Role: lead

Responsible Party

Steven Ades

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Steven Ades, MD

Role: PRINCIPAL_INVESTIGATOR

Fletcher Allen Health Care / University of Vermont College of Medicine

Locations

Fletcher Allen Health Care

Burlington, Vermont, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27628064 (View on PubMed)

Other Identifiers

VCC 0911

Identifier Type: OTHER

Identifier Source: secondary_id

VCC 0911

Identifier Type: -

Identifier Source: org_study_id