Morphine Versus Methadone As First Line Strong Opioid for Cancer Pain

NCT00634010 | Terminated Phase 3 Results DMC

• 3 other identifiers: 2007-04771R01CA124481-01A1NCI-2012-02126
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Advanced Cancer; Solid Tumors

Keywords

Advanced Cancer; Solid Tumors; Cancer Pain; Opioid Pain Killer; Morphine; Methadone

Outcome Measures

Primary Outcomes (1)

• Participant Pain Severity Score Measured Using Brief Pain Inventory

  Brief Pain Inventory (BPI): Pain severity measured with BPI, which asks participants to rate pain for last 24 hours on 0 to 10 scales at its "worst", "least", "average " and "now". The scales are presented on a 10 cm line, with each number equidistant from the next. Each scale is bounded by the words "no pain' at the 0 end and "pain as bad as you can imagine" at the other. BPI used to determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced pain over a 4 week (+/- 3 days) treatment period in participants with advanced cancer.

  Comparing baseline and pain scores at 4 weeks (+/- 3 days)

Study Arms (2)

Morphine Capsule

ACTIVE COMPARATOR

Morphine 15 mg slow release orally every 12 hours + additional doses as needed

Drug: Morphine

Methadone Capsule

ACTIVE COMPARATOR

Methadone 5 mg orally every 12 hours + additional as needed doses up to 40-50 mg/day

Drug: Methadone

Interventions

Morphine DRUG

15 mg oral every 12 Hours; additional capsules taken every 2 hours as needed.

Morphine Capsule

Methadone DRUG

5 mg orally every 12 hours; additional capsules every 2 hours as needed.

Methadone Capsule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 blood urea nitrogen (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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

LBJ General Hospital

Houston, Texas, 77030, United States

Location

The Michael E. DeBakey V.A. Medical Center

Houston, Texas, 77030, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Cancer Pain

Interventions

Morphine; Methadone

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Ketones; Organic Chemicals

Results Point of Contact

• Title: Eduardo Bruera, MD, Chair, Palliative Care Medicine
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Eduardo Bruera, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2008
• First Posted: March 12, 2008
• Study Start: February 1, 2008
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: May 9, 2016
• Results First Posted: May 9, 2016

Record last verified: 2016-04

Locations

US (3)