Morphine Versus Methadone As First Line Strong Opioid for Cancer Pain - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00634010

Purpose

Primary Aims:

To determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced pain over a 12-week treatment period in patients with advanced cancer. Previous studies have demonstrated consistent improvement of pain control after opioid rotation from morphine to methadone. In addition, the pilot study showed that there was a trend towards lower pain intensity when methadone used as first line opioid as compared to morphine. Researchers postulate that due to its superior analgesic effects, methadone will result in better pain control over time as compared to morphine.
To determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced frequency of neurotoxicity, dose escalation and treatment failure over a 12-week treatment period. Previous studies have demonstrated that patients develop increased pain or neurotoxicity after chronic use of morphine and require frequent opioid escalation. Researchers postulate that methadone will demonstrate lower opioid induced neurotoxicity, less frequent dose escalation and less treatment failure over 12-week treatment period as compared to morphine.

Secondary Aim:

-To perform an economic evaluation, comparing the costs and clinical benefits of methadone and morphine. Researchers will perform an evaluation that incorporates both treatment and potential "downstream" costs, as well as an examination of clinical benefits that incorporate preferences, to perform an appropriate economic comparison. We postulate that methadone and its associated costs will be cheaper than morphine. However, if one strategy is both more expensive and clinically superior than the other, researchers are prepared to perform an incremental cost-effectiveness analysis. In that case, researchers expect to show that the greater pharmaceutical costs involved with morphine will make its use not be a cost-effective strategy.

Condition	Intervention	Phase
Advanced Cancer Solid Tumors	Drug: Morphine Drug: Methadone	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Morphine Versus Methadone As First Line Strong Opioid for Cancer Pain

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Methadone Methadone hydrochloride

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Patient Pain Severity Score measured using Brief Pain Inventory [ Time Frame: Comparing baseline and 4 weeks (+/- 3 days) pain scores ] [ Designated as safety issue: No ]

Estimated Enrollment:	250
Study Start Date:	February 2008
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Morphine Capsule Morphine 15 mg slow release orally every 12 hours + additional doses as needed	Drug: Morphine 15 mg oral every 12 Hours; additional capsules taken every 2 hours as needed.
Active Comparator: Methadone Capsule Methadone 5 mg orally every 12 hours + additional as needed doses up to 40-50 mg/day	Drug: Methadone 5 mg orally every 12 hours; additional capsules every 2 hours as needed.

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Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient has pain caused by advanced cancer (local recurrence or metastatic disease)
Patient reporting average pain score for the last 24 hours is >/= 4 on a numerical scale from 0 to 10 (0= no pain, 10=the worst possible pain).
Patient is receiving mild opioids (e.g. propoxyphene, codeine, tramadol, hydrocodone), mixed agonist/antagonist (e.g. buprenorphine) or no opioids.
Patient requires initiation of strong opioid for cancer pain.
Patient has the ability to receive morphine or methadone orally.
Patient has no known allergy or severe toxicity to morphine or morphine-like drugs (e.g. hydromorphone, oxycodone, oxymorphone, codeine, hydrocodone, levorphanol), or methadone or methadone-like drug (e.g. propoxyphene).
Patient has normal cognition defined as normal state of arousal and absence of obvious clinical findings of confusion, memory or concentration deficit.
Patient has normal renal function (creatinine and BUN within normal limits) </= 4 weeks of study entry.
Patient's performance status (ECOG) is 3 or less.
Patient is willing to sign written informed consent.
Patient is 18 years of age or older.
Patient is able to return to clinic for evaluation by physician day 8 , 15 , 29, 57 and 85 ( +/- 3 days) during study period.

Exclusion Criteria:

Patient has concurrent strong opioid for cancer pain, such as morphine, hydromorphone, oxycodone, meperidine, fentanyl, oral transmucosal fentanyl citrate (OTFC), sufentanil, methadone, levorphanol, transdermal fentanyl.
Patient is receiving radiation therapy for pain control.
Patient is receiving drugs that interacting with methadone, such as (delavirdine, fluconazole, fluvoxamine, bravavir, amprenavir, efavirenz, lopinavir, nelfinavir, nevirapine, carbamazepine, dexamethasone (Patients receiving short term chemotherapy-related doses are permitted) , phenytoin, rifampin, or grapefruit,).
Patients are determined incapable of completing the evaluation forms.
Severe hypotension, acute or severe asthma, paralytic ileus, gastrointestinal obstruction, severe respiratory depression.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00634010

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
LBJ General Hospital
Houston, Texas, United States, 77030
The Michael E. DeBakey V.A. Medical Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Eduardo Bruera, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00634010 History of Changes
Other Study ID Numbers:	2007-0477
Study First Received:	March 5, 2008
Last Updated:	September 26, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Advanced Cancer
Solid Tumors
Cancer Pain

Opioid Pain Killer
Morphine
Methadone

Additional relevant MeSH terms:

Neoplasms
Methadone
Morphine
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics

ClinicalTrials.gov processed this record on February 09, 2012