Methadone Versus Morphine for Cancer-Related Pain

This study has been terminated.
(Slow accrual.)
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00573937
First received: December 12, 2007
Last updated: October 4, 2010
Last verified: October 2010
  Purpose

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


Condition Intervention Phase
Neoplasms
Pain
Drug: Methadone
Drug: Morphine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Methadone Versus Morphine for Moderate to Severe Cancer-Related Pain: A Double-Blind Randomized Parallel Group Study

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • The Primary Outcome Measure is Whether the Patient Had at Least 33% Reduction From the Baseline Visual Numeric Scale Score for Pain at the Time of the Visit. [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Whether the Patient Had at Least 33% Reduction From the Baseline Visual Numeric Scale Score for Pain at the Time of the Visit. [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: August 2007
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methadone Drug: Methadone
Oral methadone 2.5 mg every 8 hours, and oral methadone 2.5 mg every 4 hours as needed for breakthrough pain.
Active Comparator: Morphine
Oral slow-release morphine (15 mg) every 8 hours, and immediate-release morphine (10 mg) every 4 hours as needed for breakthrough pain.
Drug: Morphine
Oral slow-release morphine 15 mg every 8 hours, and oral immediate-release morphine 10 mg every 4 hours as needed for breakthrough pain.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00573937

Locations
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Eric E. Prommer, M.D. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Eric E. Prommer, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT00573937     History of Changes
Other Study ID Numbers: 07-003051
Study First Received: December 12, 2007
Results First Received: October 4, 2010
Last Updated: October 4, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Neoplasms
Pain
Methadone
Morphine

Additional relevant MeSH terms:
Neoplasms
Morphine
Methadone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Antitussive Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on September 18, 2014