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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pain; Cancer
• Intervention / Treatment: Drug: Sublingual Methadone

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Tom Baker Cancer Centre
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pharmacokinetic; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta
• Collaborators: University of Calgary
• Investigators: Principal Investigator: Neil Hagen, MD, AHS Cancer Control Alberta

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: July 11, 2006
• First Submitted That Met QC Criteria: July 12, 2006
• First Posted (Estimate): July 13, 2006

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 17, 2019
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: Outpatients; feasibility study; Sublingual Methadone; Cancer related breakthrough pain; Phase II/open label; Safety/ efficacy; previously receiving opioids; speak English
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Breakthrough Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Methadone
• Other Study ID Numbers: 20144; 22206