Methadone for 'Adenocarcinopathic' Pain Treatment (METHADOPT)
Cancer Pain, Adenocarcinoma
About this trial
This is an interventional treatment trial for Cancer Pain focused on measuring Cancer, Methadone, Morphine, Hydromorphone, Adenocarcinoma
Eligibility 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).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Methadone
Morphine
DESCRIPTION: Blinded methadone 1mg tablets PO -- DOSAGE: A) For patients initially taking 0-30 mg MEDD: Starting dose: 0.5mg Q4H x 4 doses + 1.0mg QHS + 0.5mg Q2H PRN (max 4 doses) First increase: 1.0 mg Q4H x 4 doses + 2.0mg QHS + 0.5mg Q2H PRN (max 4 doses) Second increase: 1.5mg Q4H x 4 doses + 3.0mg QHS + 0.5mg Q2H PRN (max 4 doses) Third increase: 2.0mg Q4H x 4 doses + 4.0mg QHS + 1.0mg Q2H PRN (max 4 doses) Fourth increase: 2.5mg Q4H x 4 doses + 5.0mg QHS + 1.0mg Q2H PRN (max 4 doses) B) For patients initially taking 31-60 mg MEDD: Starting dose: 1.0mg Q4H x 4 doses + 2.0mg QHS + 0.5mg Q2H PRN (max 4 doses) First increase: 1.5mg Q4H x 4 doses + 3.0mg QHS + 1.0mg Q2H PRN (max 4 doses) Second increase: 2.0mg Q4H x 4 doses + 4.0mg QHS + 1.0mg Q2H PRN (max 4 doses) Third increase: 2.5mg Q4H x 4 doses + 5.0mg QHS + 1.5mg Q2H PRN (max 4 doses) Fourth increase: 3.0mg Q4H x 4 doses + 6.0mg QHS + 1.5mg Q2H PRN (max 4 doses)
DESCRIPTION: Blinded morphine 5mg tablets PO -- DOSAGE: A) For patients initially taking 0-30 mg MEDD: Starting dose: 2.5mg Q4H x 4 doses + 5.0mg QHS + 2.5mg Q2H PRN (max 4 doses) First increase: 5.0 mg Q4H x 4 doses + 10.0mg QHS + 2.5mg Q2H PRN (max 4 doses) Second increase: 7.5mg Q4H x 4 doses + 15.0mg QHS + 2.5mg Q2H PRN (max 4 doses) Third increase: 10.0mg Q4H x 4 doses + 20.0mg QHS + 5.0mg Q2H PRN (max 4 doses) Fourth increase: 12.5mg Q4H x 4 doses + 25.0mg QHS + 5.0mg Q2H PRN (max 4 doses) B) For patients initially taking 31-60 mg MEDD: Starting dose: 5.0mg Q4H x 4 doses + 10.0mg QHS + 2.5mg Q2H PRN (max 4 doses) First increase: 7.5mg Q4H x 4 doses + 15.0mg QHS + 5.0mg Q2H PRN (max 4 doses) Second increase: 10.0mg Q4H x 4 doses + 20.0mg QHS + 5.0mg Q2H PRN (max 4 doses) Third increase: 12.5mg Q4H x 4 doses + 25.0mg QHS + 12.5mg Q2H PRN (max 4 doses) Fourth increase: 15.0mg Q4H x 4 doses + 30.0mg QHS + 12.5mg Q2H PRN (max 4 doses)