NeoplasmsPhase 2NCT01004393
Methylnaltrexone for Opioid-induced Constipation in Cancer Patients
A Phase 2 study testing Methylnaltrexone bromide in people with Neoplasms and Constipation, run by University of Vermont at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Constipation, Opioid-Related Disorders
- What is being tested?
- Methylnaltrexone bromide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Dec 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Fletcher Allen Health Care
Burlington, Vermont, 05401
About this study
Official title: Phase II Trial of Subcutaneous Methylnaltrexone in the Treatment of Severe Opioid-induced Constipation in Cancer Patients
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.
Read the 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
- Being tested
- Methylnaltrexone bromide
- Keywords
- Methylnaltrexone, Constipation, Narcotic Antagonists, Analgesics, Opioid, Neoplasms
- Medical subject headings
- Neoplasms, Constipation, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylnaltrexone bromideDrug
Also called Relistor
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
| Study group | Role | What they receive |
|---|---|---|
| Methylnaltrexone bromide | Experimental | 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. Receives: Drug: Methylnaltrexone bromide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone
Measured: 4 hours after the dose of subcutaneous methylnaltrexone
Secondary outcomes (7)
Laxation After Administration of Subcutaneous Methylnaltrexone
Measured: 24 and 48 hours after the dose of subcutaneous methylnaltrexone
Time to Laxation After Administration of Subcutaneous Methylnaltrexone
Measured: 48 hours after the dose of subcutaneous methylnaltrexone
Overall Pain Scores (0-10; 0=no Pain, 10=Worst Pain) After Administration of Subcutaneous Methylnaltrexone
Measured: 48 hours after the dose of subcutaneous methylnaltrexone
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
Measured: 48 hours after the dose of subcutaneous methylnaltrexone
Bowel Movement Assessment (Frequency, Consistency and Difficulty) After Administration of Subcutaneous Methylnaltrexone
Measured: 48 hours after the dose of subcutaneous methylnaltrexone
Constipation Assessment (Severity and Distress) After Administration of Subcutaneous Methylnaltrexone
Measured: 48 hours after the dose of subcutaneous methylnaltrexone
Patient Satisfaction With the Study Medication After Administration of Subcutaneous Methylnaltrexone
Measured: 48 hours after the dose of subcutaneous methylnaltrexone
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vermont
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven Ades, University of Vermont
- Investigators
- Steven Ades, MD, Principal investigator, Fletcher Allen Health Care / University of Vermont College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01004393
- Sponsor's protocol ID
- VCC 0911
- Other IDs
- VCC 0911
- Status last verified
- Dec 2015
- First submitted
- 28 Oct 2009
- Last updated
- 2 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27628064
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Subcutaneous Methylnaltrexone in the Treatment of Severe Opioid-induced Constipation in Cancer Patients
- ClinicalTrials.gov ID
- NCT01004393
- Acronym / sponsor ID
- VCC 0911
- Conditions
- Neoplasms, Constipation, Opioid-Related Disorders
- Keywords
- Methylnaltrexone, Constipation, Narcotic Antagonists, Analgesics, Opioid, Neoplasms
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of VermontUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 29 Oct 2009 (estimated)
- Results
- Posted 2 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Methylnaltrexone bromide | Experimental | Drug: Methylnaltrexone bromideA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylnaltrexone bromideAlso: RelistorMethylnaltrexone 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 | Drug | Methylnaltrexone bromide |
Primary outcome
Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone
Time frame: 4 hours after the dose of subcutaneous methylnaltrexone
7 secondary outcomes
Laxation After Administration of Subcutaneous Methylnaltrexone
Time frame: 24 and 48 hours after the dose of subcutaneous methylnaltrexone
Time to Laxation After Administration of Subcutaneous Methylnaltrexone
Time frame: 48 hours after the dose of subcutaneous methylnaltrexone
Overall Pain Scores (0-10; 0=no Pain, 10=Worst Pain) After Administration of Subcutaneous Methylnaltrexone
Time frame: 48 hours after the dose of subcutaneous methylnaltrexone
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
Time frame: 48 hours after the dose of subcutaneous methylnaltrexone
Bowel Movement Assessment (Frequency, Consistency and Difficulty) After Administration of Subcutaneous Methylnaltrexone
Time frame: 48 hours after the dose of subcutaneous methylnaltrexone
Constipation Assessment (Severity and Distress) After Administration of Subcutaneous Methylnaltrexone
Time frame: 48 hours after the dose of subcutaneous methylnaltrexone
Patient Satisfaction With the Study Medication After Administration of Subcutaneous Methylnaltrexone
Time frame: 48 hours after the dose of subcutaneous methylnaltrexone
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27628064Mori 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Ades, MD principal investigator
Fletcher Allen Health Care / University of Vermont College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methylnaltrexone bromide in people with Neoplasms and Constipation, run by University of Vermont at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rescue-free Laxation After Administration of Subcutaneous Methylnaltrexone (time frame: 4 hours after the dose of subcutaneous methylnaltrexone). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01004393, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2016.