Using methadone to relieve painful nerve damage from chemotherapy

Methadone to Treat Painful Chemotherapy Induced Peripheral Neuropathy (METACIN): a Randomized Double-blind Controlled Trial

This study is testing whether methadone can help cancer patients with painful nerve damage from chemotherapy feel better compared to a common medication called duloxetine.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: University of British Columbia (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 4 sites (Nanaimo, British Columbia and 3 other locations)
• Trial ID: NCT05786599 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of methadone compared to duloxetine in treating chemotherapy-induced peripheral neuropathy (CIPN), a painful condition affecting many cancer patients. It involves adult participants with a cancer diagnosis who have experienced moderate to severe nerve pain for at least three months after chemotherapy. The study employs a double-blind, double-dummy randomized controlled design, where participants will be assigned to receive either methadone or duloxetine over a five-week period, with weekly follow-ups to assess pain reduction and quality of life improvements.

Who should consider this trial

Good fit: Ideal candidates are adult cancer patients with a life expectancy greater than 12 weeks and moderate to severe CIPN lasting at least three months after chemotherapy.

Not a fit: Patients with other causes of peripheral neuropathy or severe psychiatric or medical conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients suffering from painful CIPN, potentially improving their quality of life.

How similar studies have performed: While duloxetine is the only recommended treatment for CIPN, studies on methadone for neuropathic pain in cancer patients suggest it may be a promising alternative, though this specific approach has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age \>18 years old.
2. Estimated life expectancy greater than 12 weeks.
3. Opioid naïve or oral morphine equivalent use \<60 mg/day.
4. Greater than grade 1 CIPN based on CTCAE.
5. \>3/10 average CIPN-related neuropathic pain lasting ≥3 months beyond chemotherapy completion.
6. A cancer diagnosis.
7. Treatment with one of the following neurotoxic chemotherapies: platinums, taxanes, vinca alkaloids, bortezomib, or thalidomide.

Exclusion Criteria:

1. Other causes of peripheral neuropathy.
2. The following psychiatric illnesses: severe depression, suicidality, bipolar disease or psychotic disorder, alcohol or substance use disorder, DSM V criteria eating disorder.
3. The following medical illnesses: known or suspected mechanical gastrointestinal obstruction or any disease/conditions that affect bowel transit, suspected surgical abdomen, acute or severe asthma, COPD, acute respiratory depression, elevated serum CO2 and cor pulmonale, delirium tremens, convulsive disorders, severe CNS depression such as from cerebrospinal or intracranial pressure and head injury, diarrhea from pseudomembranous colitis, leptomeningeal disease.
4. Liver or renal dysfunction within the last 90 days as defined by MELD-Na score ≥17 and GFR ≤30 ml/min respectively.
5. QTC \>499ms within last 90 days.
6. Current pregnancy or lactation.
7. Inability to take oral medications.
8. Positive CAGE and/or Opioid Risk Tool - Revised questionnaire
9. Known allergy or hypersensitivity to opioids, duloxetine, or any ingredient in their formulation.
10. Concomitant use of excluded medications: methadone, other antidepressants (including within 14 days of discontinuing monoamine oxidase inhibitors), thioridazine, potent CYP1A2 inhibitors (such as fluvoxamine and some quinolone antibiotics).
11. Uncontrolled narrow-angle glaucoma.
12. If women of child-bearing potential (i.e. Menstruation within \<2 years) are unable or unwilling to use Health Canada approved highly effective methods of contraception (hormonal contraceptives, intrauterine device or system, vasectomy, tubal ligation, or double barrier method), or abstinence during the treatment period.

Note: Any use of prior co-analgesics will be continued (and must have been stable for more than 2 weeks), but the use of new co-analgesics or titration of current co-analgesics will not be permitted during the trial.

Where this trial is running

Nanaimo, British Columbia and 3 other locations

• Nanaimo Regional Hospital — Nanaimo, British Columbia, Canada (Not_yet_recruiting)
• BC Cancer Surrey — Surrey, British Columbia, Canada (Recruiting)
• BC Cancer Vancouver — Vancouver, British Columbia, Canada (Not_yet_recruiting)
• BC Cancer Victoria — Victoria, British Columbia, Canada (Not_yet_recruiting)

Conditions Chemotherapy-induced Peripheral Neuropathy