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Methadone Hydrochloride as First-Line Therapy in Treating Patients With Chronic Neuropathic Cancer Pain

Primary Purpose

Nausea and Vomiting, Pain, Sleep Disorders

Status
Terminated
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
methadone hydrochloride
questionnaire administration
management of therapy complications
Sponsored by
NCIC Clinical Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Nausea and Vomiting focused on measuring sleep disorders, nausea and vomiting, unspecified adult solid tumor, protocol specific, pain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Patients diagnosed with cancer and experiencing chronic neuropathic pain syndrome

    • Pain syndrome diagnosed by the investigator
    • Pain syndrome related to the effects of cancer or its treatment (i.e., chemotherapy, radiotherapy, and surgery)

    • Meets 1 of the following criteria:

      • Need to be started on strong opioids
      • Require an increase in opioid dose and are currently taking ≤ 75 mg of total daily dose of oral morphine equivalent
  • Experiencing pain for ≥ 4 weeks with an average pain score of ≥ 4 or a worst pain score of ≥ 5 (using the 0-10 Brief Pain Inventory Scale) during the past 24 hours
  • Requires strong opioids to control pain and is using an oral morphine-equivalent dose of 0-75 mg per day, on average, including breakthrough analgesia, within the past 3 full calendar days
  • Mixed pain syndrome allowed provided the neuropathic component is the predominant pain

  • Meets 1 of the following criteria:

    • Receiving concurrent chemotherapy but the chronic neuropathic pain is not related to this treatment and is not expected to improve or worsen because of this therapy
    • Received prior chemotherapy but discontinued treatment, has not received chemotherapy within the past 7 days, and no further chemotherapy is planned
    • No prior chemotherapy

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 40-100%
  • ALT and AST ≤ 3 times upper limit of normal (ULN)
  • Creatinine ≤ 2 times ULN
  • No other known laboratory abnormality that, in the investigator's opinion, would contraindicate study participation
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Mini-Mental State Examination score ≥ 25/30
  • Able to speak, read, and write in either English or French
  • Willing to complete study diary and questionnaires
  • Available for study treatment and follow up (i.e., within reasonable geographical limits of the participating center)
  • Able to swallow and tolerate oral medications
  • Patients with prior exposure to methadone hydrochloride must be able to tolerate it
  • No intractable nausea and vomiting

  • No presence or history of unstable disease or condition that would, in the investigator's opinion, preclude patient participation in study treatment, such as:

    • Head injury
    • Increased intracranial pressure
    • Uncontrolled seizures
    • Uncontrolled asthma
    • Decompensated chronic obstructive pulmonary disease
    • Untreated prostate hypertrophy
    • Acute abdominal conditions
    • Untreated hyperthyroidism and Addison disease
    • Increased cerebrospinal fluid pressure
    • Urethral stricture
    • Severe cardiac arrhythmias (especially prolonged QT interval)
    • Symptomatic hypotension
    • Toxic psychosis
    • Cor pulmonale
    • Sleep apnea
    • Severe obesity
    • Kyphoscoliosis
    • Myxedema
    • Central nervous system depression
    • Coma
  • No history of significant alcohol, analgesic, or narcotic substance abuse within the past 6 months
  • Able physically and mentally to answer questions and comply with study treatment
  • No patient who lives alone and cannot access at least 1 caregiver who can monitor on a daily basis at home

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 3 weeks since prior radiopharmaceutical treatment or radiotherapy
  • Concurrent co-analgesics and medications that can affect methadone hydrochloride metabolism allowed provided patients have been on a stable dose for the past 3-5 days and ≥ 5 half lives have passed since any change in dose
  • Not scheduled to start chemotherapy during the study treatment
  • Not planning on starting or discontinuing medication associated with modified methadone hydrochloride clearance during study treatment
  • No concurrent therapeutic procedure that is likely to influence pain intensity during the study period
  • No concurrent other opioid medications
  • No other concurrent methadone hydrochloride

Sites / Locations

  • Cross Cancer Institute
  • BCCA - Cancer Centre for the Southern Interior
  • BCCA - Vancouver Cancer Centre
  • CancerCare Manitoba
  • Cancer Centre of Southeastern Ontario at Kingston
  • Univ. Health Network-Princess Margaret Hospital
  • McGill University - Dept. Oncology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Arm A: Methadone

Arm B: Methadone

Arm Description

Level 1: 1 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA** per day) Level 2: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 1: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 2: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 4 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Outcomes

Primary Outcome Measures

Optimum starting dose

Secondary Outcome Measures

Pain control as assessed by the number and timing of breakthrough analgesics, the number of episodes of breakthrough pain, the total daily dose of methadone, and the average pain scores
Adverse events (including respiratory depression) according to NCI CTCAE v3.0 criteria
Frequency and severity of sleep disturbance from pain
Feasibility of recruiting patients

Full Information

First Posted
June 27, 2009
Last Updated
August 3, 2023
Sponsor
NCIC Clinical Trials Group
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1. Study Identification

Unique Protocol Identification Number
NCT00930332
Brief Title
Methadone Hydrochloride as First-Line Therapy in Treating Patients With Chronic Neuropathic Cancer Pain
Official Title
A Phase I Study to Determine the Dose of Methadone as a First Line Agent in the Treatment of Chronic Neuropathic Cancer Pain
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual
Study Start Date
June 17, 2010 (Actual)
Primary Completion Date
April 8, 2011 (Actual)
Study Completion Date
January 6, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NCIC Clinical Trials Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Methadone hydrochloride may reduce chronic neuropathic pain in patients with cancer. PURPOSE: This phase I trial is studying the side effects and best dose of methadone hydrochloride as first-line therapy in treating patients with chronic neuropathic cancer pain.
Detailed Description
OBJECTIVES: Primary To determine the optimum starting dose (defined as the dose that does not require modification within the first 4 days of treatment for lack of efficacy or the occurrence of adverse events) of methadone hydrochloride as a first-line opioid treatment in patients with chronic neuropathic cancer pain. Secondary To assess the number and timing of breakthrough analgesic usage. To assess the number of episodes of breakthrough pain. To assess the total daily dose of methadone hydrochloride. To assess the average pain score. To determine the safety and adverse event profile of methadone hydrochloride as a first-line opioid in the treatment of chronic neuropathic cancer pain. To assess the frequency and severity of sleep disturbance associated with the use of methadone hydrochloride. To determine the feasibility of recruiting patients with chronic neuropathic cancer pain in a reasonable time frame for a future phase III study of methadone hydrochloride vs morphine. OUTLINE: This is a multicenter study. Patients are assigned to a group according to their average daily dosage of morphine-equivalent for the 3 full days prior to study entry (≤ 45 mg/day OR > 45 but ≤ 75 mg/day). Patients receive oral methadone hydrochloride at various doses every 8 hours. Patients also may receive breakthrough oral methadone hydrochloride every 2 hours, as needed, for up to 6 breakthrough analgesics per day. Treatment continues for up to 35 days. Treatment stops if the patient has well-controlled pain or experiences intolerable side effects. Patients complete the Short-Form McGill Pain Questionnaire at baseline. Patients rate their pain according to questions from the Brief Pain Inventory on a scale of 0 (no pain) to 10 (worst pain imaginable) to best describe pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on average, and pain right now; record the number and timing of breakthrough analgesic usage, the number of episodes of breakthrough pain, and the total daily dose of methadone hydrochloride; and complete nausea and sleep assessments once daily on days 1-14. After completion of study treatment, patients are followed at 4, 6-7, and 28 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nausea and Vomiting, Pain, Sleep Disorders, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
sleep disorders, nausea and vomiting, unspecified adult solid tumor, protocol specific, pain

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: Methadone
Arm Type
Active Comparator
Arm Description
Level 1: 1 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA** per day) Level 2: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)
Arm Title
Arm B: Methadone
Arm Type
Active Comparator
Arm Description
Level 1: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 2: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 4 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)
Intervention Type
Drug
Intervention Name(s)
methadone hydrochloride
Intervention Description
Level 1: 1 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA** per day) Level 2: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 3mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) OR Level 1: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 2: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 4 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)
Intervention Type
Other
Intervention Name(s)
questionnaire administration
Intervention Description
within 48 hours of registration
Intervention Type
Procedure
Intervention Name(s)
management of therapy complications
Intervention Description
if required
Primary Outcome Measure Information:
Title
Optimum starting dose
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Pain control as assessed by the number and timing of breakthrough analgesics, the number of episodes of breakthrough pain, the total daily dose of methadone, and the average pain scores
Time Frame
28 days
Title
Adverse events (including respiratory depression) according to NCI CTCAE v3.0 criteria
Time Frame
28 days
Title
Frequency and severity of sleep disturbance from pain
Time Frame
28 days
Title
Feasibility of recruiting patients
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Patients diagnosed with cancer and experiencing chronic neuropathic pain syndrome Pain syndrome diagnosed by the investigator Pain syndrome related to the effects of cancer or its treatment (i.e., chemotherapy, radiotherapy, and surgery) Meets 1 of the following criteria: Need to be started on strong opioids Require an increase in opioid dose and are currently taking ≤ 75 mg of total daily dose of oral morphine equivalent Experiencing pain for ≥ 4 weeks with an average pain score of ≥ 4 or a worst pain score of ≥ 5 (using the 0-10 Brief Pain Inventory Scale) during the past 24 hours Requires strong opioids to control pain and is using an oral morphine-equivalent dose of 0-75 mg per day, on average, including breakthrough analgesia, within the past 3 full calendar days Mixed pain syndrome allowed provided the neuropathic component is the predominant pain Meets 1 of the following criteria: Receiving concurrent chemotherapy but the chronic neuropathic pain is not related to this treatment and is not expected to improve or worsen because of this therapy Received prior chemotherapy but discontinued treatment, has not received chemotherapy within the past 7 days, and no further chemotherapy is planned No prior chemotherapy PATIENT CHARACTERISTICS: Karnofsky performance status 40-100% ALT and AST ≤ 3 times upper limit of normal (ULN) Creatinine ≤ 2 times ULN No other known laboratory abnormality that, in the investigator's opinion, would contraindicate study participation Not pregnant or nursing Fertile patients must use effective contraception Mini-Mental State Examination score ≥ 25/30 Able to speak, read, and write in either English or French Willing to complete study diary and questionnaires Available for study treatment and follow up (i.e., within reasonable geographical limits of the participating center) Able to swallow and tolerate oral medications Patients with prior exposure to methadone hydrochloride must be able to tolerate it No intractable nausea and vomiting No presence or history of unstable disease or condition that would, in the investigator's opinion, preclude patient participation in study treatment, such as: Head injury Increased intracranial pressure Uncontrolled seizures Uncontrolled asthma Decompensated chronic obstructive pulmonary disease Untreated prostate hypertrophy Acute abdominal conditions Untreated hyperthyroidism and Addison disease Increased cerebrospinal fluid pressure Urethral stricture Severe cardiac arrhythmias (especially prolonged QT interval) Symptomatic hypotension Toxic psychosis Cor pulmonale Sleep apnea Severe obesity Kyphoscoliosis Myxedema Central nervous system depression Coma No history of significant alcohol, analgesic, or narcotic substance abuse within the past 6 months Able physically and mentally to answer questions and comply with study treatment No patient who lives alone and cannot access at least 1 caregiver who can monitor on a daily basis at home PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 3 weeks since prior radiopharmaceutical treatment or radiotherapy Concurrent co-analgesics and medications that can affect methadone hydrochloride metabolism allowed provided patients have been on a stable dose for the past 3-5 days and ≥ 5 half lives have passed since any change in dose Not scheduled to start chemotherapy during the study treatment Not planning on starting or discontinuing medication associated with modified methadone hydrochloride clearance during study treatment No concurrent therapeutic procedure that is likely to influence pain intensity during the study period No concurrent other opioid medications No other concurrent methadone hydrochloride
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Gagnon, MD, MSC
Organizational Affiliation
McGill Cancer Centre at McGill University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ray Viola
Organizational Affiliation
Queen's University
Official's Role
Study Chair
Facility Information:
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
BCCA - Cancer Centre for the Southern Interior
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1Y 5L3
Country
Canada
Facility Name
BCCA - Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
CancerCare Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 0V9
Country
Canada
Facility Name
Cancer Centre of Southeastern Ontario at Kingston
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5P9
Country
Canada
Facility Name
Univ. Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
McGill University - Dept. Oncology
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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Methadone Hydrochloride as First-Line Therapy in Treating Patients With Chronic Neuropathic Cancer Pain

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