Methadone for 'Adenocarcinopathic' Pain Treatment

• Status: Not yet recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Methadone is an opioid that has been used for over 80 years to treat various types of pain, including cancer pain. Despite its increasing popularity as a co-analgesic and first-line treatment for cancer pain, there remain some outstanding questions regarding its use in treating cancer pain, such as its efficacy compared to other opioids and its appropriateness as a first-line treatment. We will conduct a Vanguard Randomized Clinical Trial (RCT) to estimate the efficacy of methadone compared to morphine for the treatment of a newly defined type of cancer pain, which we have termed 'adenocarcinopathic' pain (ACPP).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ottawa Hospital Research Institute
• Collaborators: Bruyere Research Institute; The Ottawa Hospital
• Treatments: Methadone; Morphine

Criteria

Inclusion Criteria:

• Cancer type is adenocarcinoma;

• In the physician's opinion, mechanism of pain is most likely linked to an adenocarcinoma 'in proximity to' or invading a nerve or nerve plexus (i.e., 'adenocarcinopathic' pain; ACPP);

• Experiencing poorly controlled pain (defined as pain of 4 or higher on a 10-point visual analogue scale) despite the use of non-opioid analgesics or despite the regular use of up to 60 mg morphine equivalent daily dose (MEDD);

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2;

• Estimated prognosis of at least 3 months;

• Able to fill out questionnaires and understand procedures in English and/or French;

• Able to provide first person informed consent;

• Physician deems it appropriate to start the patient on the opioid.

Exclusion Criteria:

• Known QTc prolongation (QTc greater than 500ms, QRS less than 120ms) or known congenital QTc prolongation syndrome;

• Taking at least one medication that increases risk of Torsades de Pointes (TdP):

cisapride, disopyramide, dofetilide, flecainide, procainamide, propafenone, quinidine, quinine, sotalol;

• History of opioid abuse or dependence using Edmonton Pain Classification;

• Has geographic difficulties with follow-up in person;

• Has any of the following comorbidities: documented class 3 or 4 New York Heart Association (NYHA) heart failure, myocardial infarction in the last 3 months, unstable angina, pericardial disease, oxygen dependent pulmonary diseases, Parkinson's disease, suspected or diagnosed dementia, bipolar disorder, poorly managed major depression (current or treated) or anxiety disorder;

• Taking medication known to have clinically significant interactions with the CYP450 enzyme: carbamazepine, efavirenz, phenobarbital, rifampicin, azole antifungals, antiretrovirals, grapefruit juice, clarithromycin, erythromycin;

• Diagnosed with Child-Pugh class B and/or C cirrhosis;

• Has hepatic insufficiency, defined as jaundice with irreversible hyperbilirubinemia of at least 34 micromol/L despite biliary tract stents (severity criteria in Child-Pugh-Turcotte score);

• Received radiation or any nerve block or plexus block on the same side as the pain in the past 14 days or PLANNED within the next 14 days;

• PLANNED prescription for daily co-analgesia with pregabalin, gabapentin, or dexamethasone during the next 14 days (not including dexamethasone with chemotherapy);

• Taking medication associated with major risk of serotonin syndrome (monoamine oxidase inhibitors; MAOIs): linezolid, moclobemide, rasagiline, selegiline;

• Taking medication known to be an opioid agonist, antagonist, or partial agonist:

naltrexone, buprenorphine, tapentadol, tramadol;

• Other negative characteristic as per physician discretion (e.g., reduced renal function).