A Phase I Study to Determine the Dose of Methadone as a First Line Agent in the Treatment of Chronic Neuropathic Cancer Pain
- 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.
- 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
- 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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Optimum starting dose
Bruno Gagnon, MD, MSC
McGill Cancer Centre at McGill University
Canada: Ethics Review Committee