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

Phase 1

Terminated

• Conditions: Nausea and Vomiting; Unspecified Adult Solid Tumor, Protocol Specific; Pain; Sleep Disorders
• Interventions: Drug: methadone hydrochloride; Other: questionnaire administration; Procedure: management of therapy complications

• Registration Number: NCT00930332
• Lead Sponsor: NCIC Clinical Trials Group

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.

Study Timeline

• Study First Submitted: 2009-06-27
• Study First Submitted QC: 2009-06-27
• Study First Posted: 2009-06-30
• Study Start: 2010-06-17
• Primary Completion: 2012-01-06
• Study Completion: 2012-01-06
• Status Verified: 2020-04
• Last Update Submitted: 2024-02-09
• Last Update Posted: 2024-02-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm B: Methadone	methadone hydrochloride	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)
Arm A: Methadone	methadone hydrochloride	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 A: Methadone	questionnaire administration	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 A: Methadone	management of therapy complications	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 B: Methadone	questionnaire administration	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)
Arm B: Methadone	management of therapy complications	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)

Primary Outcome Measures

Name	Time	Method
Optimum starting dose	28 days

Secondary Outcome Measures

Name	Time	Method
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	28 days
Feasibility of recruiting patients	28 days
Adverse events (including respiratory depression) according to NCI CTCAE v3.0 criteria	28 days
Frequency and severity of sleep disturbance from pain	28 days

Trial Locations

Locations (7)

Cancer Centre of Southeastern Ontario at Kingston; 🇨🇦 Kingston, Ontario, Canada

CancerCare Manitoba; 🇨🇦 Winnipeg, Manitoba, Canada

BCCA - Vancouver Cancer Centre; 🇨🇦 Vancouver, British Columbia, Canada

BCCA - Cancer Centre for the Southern Interior; 🇨🇦 Kelowna, British Columbia, Canada

Cross Cancer Institute; 🇨🇦 Edmonton, Alberta, Canada

McGill University - Dept. Oncology; 🇨🇦 Montreal, Quebec, Canada

Univ. Health Network-Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada