Methadone Versus Morphine for Cancer-Related Pain

Mayo Clinic

Status and phase

Terminated

Phase 2

Conditions

Neoplasms

Pain

Treatments

Drug: Methadone

Drug: Morphine

Study type

Interventional

Funder types

Other

Identifiers

NCT00573937

07-003051

Details and patient eligibility

About

The purpose of this study is to compare methadone with morphine in the management of moderate to severe cancer pain.

Full description

Treatment of cancer pain is based on the World Health Organization (WHO) step ladder approach to the use of analgesic drugs. Medication potency increases at each step of the WHO ladder, from nonopioid (step 1; e.g., aspirin and nonsteroidal anti-inflammatory drugs) through weak opioids (step 2; e.g. codeine) plus a nonopioid to strong opioids (step 3; e.g., morphine) plus a nonopioid analgesic. Morphine is considered the gold standard for the treatment of moderate to severe pain, but this is based on level C criteria. Research has discovered that methadone is a potent opioid that operates at several levels which are important for pain control. The primary aim is to compare morphine versus methadone as a first-line analgesic in patients with moderate to severe cancer pain. Patients will be randomized to receive either oral slow-release morphine (15 mg) every 8 hours and immediate-release morphine (10 mg) every 4 hours as needed for breakthrough pain or oral methadone 2.5 mg every 8 hours and methadone 2.5 mg every 4 hours as needed for breakthrough pain. Our hypothesis is that methadone will provide equivalent pain control efficacy after 4 weeks of therapy. We postulate that methadone will be as preferable as morphine as an analgesic. We will compare the two drugs via adverse effects and compare stability of analgesia via comparison of the number of breakthrough pain episodes. The study will attempt to establish equivalency of methadone as a first-line analgesic for moderate to severe cancer pain.

Enrollment

1 patient

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Must have a telephone
Age: patient must be 18 years or older and less than 70 years of age
Life expectancy of 3 months or greater
No prior use of step-3 opioids (step 2 opioids are allowed)
Provision of informed consent
Score of 26 or greater on Mini-Mental Status Exam (MMSE) (to be done by investigator if there is question about mental status)
Nonmalignant pain will be excluded; however, if the patient has both malignant and nonmalignant pain, entry into the trial will be determined by the predominant site of pain
Moderate to severe cancer related pain that requires the use of step-3 opioids
Normal renal function
There will be no exclusionary criteria based on Karnofsky score
Must live no more than 1 hour away from clinic
Patient must have pain severity of 5-7/10 on a 0-10 pain scale

Exclusion criteria

Nursing home patients
Obvious cognitive dysfunction
Intractable nausea or vomiting
A true allergy or intolerance to opioids
Unstable renal function
Undergoing therapeutic procedures likely to influence pain during the study period
Gastrointestinal pathology or surgery that influences absorption of morphine or methadone
Must not have had treatment with radiotherapy, chemotherapy or radionuclides in the last 30 days
History of drug seeking behavior
Respiratory compromise
Treatment with bisphosphonates within the last month
Use of MAO inhibitors
Drugs that interfere with CYP34A or CYP2D6
Drugs that interfere with morphine metabolism
Retroviral therapies
Active radiation or antineoplastic therapies
Hepatic dysfunction
As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study
Study will exclude women who are pregnant and/or nursing
Women who are of child bearing potential must have a negative urine pregnancy test
Patients with a recent substance abuse history will be excluded
Patients with major depression will be excluded