Sublingual Methadone for the Management of Cancer-related Breakthrough Pain in Outpatients

Study Overview
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Brief Summary
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The purpose of this Phase II study is to determine the feasibility of the dose titration and assessment protocol in the outpatient population before conducting an appropriately powered phase III study. Thus the primary purpose of this study is to determine the proportion of patients who are successfully titrated to an optimal dose of sublingual (Under the tongue) methadone and then studied at that optimal dose with successive episodes of breakthrough pain.

Official Title
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Sublingual Methadone for the Management of Cancer-related Breakthrough Pain in Outpatients: a Phase II Multicenter, Open Label, Feasibility Study

Conditions
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Cancer, Pain

Intervention / Treatment
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* Drug: Sublingual Methadone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pain due to cancer or its treatment; controlled baseline pain; episodes of breakthrough pain every day that are 4/10 in severity or greater, ; ast 10 minutes or longer, and are responsive to short acting oral opioids such as morphine or hydromorphone; are able to hole a volume of 1.0cc of water under the tongue for a 5-minute period; are able to provide written informed consent; are able to fill out the study forms Exclusion Criteria: Severe underlying respiratory disease such that an investigator is wary about the risk of respiratory failure from modest doses of opioid; prior sensitivity to methadone; currently are being administered methadone; have breakthrough pain that in the opinion of the investigator is likely to change within the next seven days (recent or imminent radiation therapy to the main site of pain, new chemotherapy or use of an injectable bisphosphonate likely to alter the pain, new use corticosteroids within the past week with a corresponding change in pain, or other interventions judged likely to alter pain); are clinically unstable or have a life expectancy of less than one month making completion of the trial unlikely

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pharmacokinetic<br>One episode of breakthrough pain was to be evaluated per patient. Clinical status and bloodwork was evaluated prior to entering into this phase of the trial, and patients were eligible if bloodwork demonstrated a HgB of >90 g/L with no concurrent bleeding. A peripheral intravenous catheter was inserted and saline locked. When breakthrough pain was experienced, methadone was administered, and the patient completed a pain intensity numeric rating scale at time 0 and every 10 minutes for one hour. A 10 cc specimen of blood was collected prior to administration of methadone, and again every 10 minutes for one hour. Blood was collected without anticoagulant, allowed to clot, separated by centrifugation, and serum samples flash frozen. Serum methadone levels were quantified by LC/MS/MS with comparison to isotopically labeled internal standards | Drug: Sublingual Methadone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to demonstrate the feasibility of a novel model to assess sublingual methadone to breakthrough pain in the outpatient setting |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to develop a model of PK/PD study of breakthrough pain |  | Baseline to 5 years | 
| to develop a research tool, the Breakthrough Pain Assessment Tool (BPAT) |  | Baseline to 5 years | 
| to demonstrate proof of concept |  | Baseline to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sublingual Methadone, Cancer related breakthrough pain, feasibility study, Phase II/open label, Outpatients, Safety/ efficacy, previously receiving opioids, speak English