Role of Methadone As Co-Opioid Analgesic

NCT00558870 | Terminated Phase 2 Results DMC

• 2 other identifiers: 2006-0641NCI-2012-01553
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: Primary Objective: To determine whether the addition of low dose methadone to morphine(in the methadone group) has a lower dose escalation index as compared to the morphine alone(in the morphine group) at Day 15 (+/- 3 days) Secondary Objectives: To determine whether individuals on the methadone arm have lower pain intensity than the morphine alone arm as demonstrated by a decrease in two points from baseline (+/- 3 days) in their ESAS score at Day 15 (+/- 3 days). To determine whether the methadone group of experiences fewer opioid induced neurotoxic side effects (including sedation, myoclonus, hallucinations, hyperalgesia and confusion) as compared to the morphine alone group at Day 15 (+/- 3 days).

Conditions

Pain

Keywords

Solid Tumors; Morphine; Methadone; Co-Opioid Analgesic; Pain

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Objective Response (OR)

  Objective response (OR) is defined as a dose escalation index \<20 where Opioid escalation index measured in milligrams is calculated by the formula, (OMD-OSD)/days, OMD = Opioid maximum dose as expressed in equianalgesic dose of oral morphine in milligrams, OSD= Opioid starting dose at the time of referral to palliative care/ pain specialist for the treatment of cancer pain as expressed in equianalgesic dose of oral morphine in milligrams. A low index indicates the achievement of adequate analgesia or appearance of uncontrollable side effects limiting upward titration over time. OR used in determining whether the addition of low dose methadone to morphine (in the methadone group) has a lower dose escalation index as compared to the morphine alone (in the morphine group) at Day 15.

  Day 15 (+/- 3 days)

• Dose Escalation Index at Day 15 (+/- 3 Days)

  Intended index period from baseline to Day 15 to determine whether the addition of low dose methadone to morphine (in the methadone group) has a lower dose escalation index as compared to the morphine alone (in the morphine group) at Day 15 (+/- 3 days). To determine whether the methadone group of individuals has a lower dose escalation index as compared to the morphine alone group: Participant dosages measured at baseline and daily until end of study (day 15), total daily dose of methadone converted to daily morphine equivalent daily dose for cancer pain and added to total daily morphine dosages. From these daily values, maximum dose recorded will be Opioid Maximum Dose (OMD). Opioid escalation index measured as described in Outcome 1 above (milligrams calculated by formula, (OMD-OSD)/days). Low index indicates achievement of adequate analgesia or appearance of uncontrollable side effects limiting upward titration over time.

  Day 15 (+/- 3 days)

Study Arms (2)

Morphine Only

ACTIVE COMPARATOR

Morphine - Arm 1: 2 Doses of "Slow-Release" Morphine PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days)."Immediate-release" morphine may be used, if needed, for pain.

Drug: Morphine

Morphine + Methadone

ACTIVE COMPARATOR

Arm 2: 1 Dose of Slow-Release Morphine PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days).)."Immediate-release" morphine may be used, if needed, for pain. 1 Dose of Methadone PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days)

Drug: Morphine; Drug: Methadone

Interventions

Morphine DRUG

Arm 1: 2 Doses of "Slow-Release" Morphine PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days)."Immediate-release" morphine may be used, if needed, for pain.

Morphine + Methadone; Morphine Only

Methadone DRUG

1 Dose of Methadone PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days) Arm 2: 1 Dose of Slow-Release Morphine PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days).)."Immediate-release" morphine may be used, if needed, for pain.

Morphine + Methadone

Eligibility Criteria

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

You may qualify if:

• Individual reporting average pain score for the last 24 hours that is at least a 4 on a numerical scale from 0 to 10 (0= no pain, 10=the worst possible pain) with a history of cancer (active or no evidence of disease).
• Individual is receiving strong opioids (morphine, fentanyl, oxycodone, hydromorphone) for 3 weeks prior to enrollment.
• Individual requires at least 150 mg of daily morphine equivalent daily dose for cancer pain. Using the formula MEDD = dose X MEDD Factor (App L) it would be follows: morphine: a 24 hour total oral intake (sum of PRN and around the clock doses) of 150 mg or greater would qualify the patient, for fentanyl alone: a 24 hour total transdermal intake of 75mcg/h or greater would qualify the patient, for oxycodone alone: a 24 hour total oral intake of 100 mg or greater would qualify the patient, and for hydromorphone alone: a 24 hour total oral intake of 30 mg/day or greater would qualify the patient.
• Individual has the ability to receive morphine or methadone orally.
• Individual has no known allergy of history of severe toxicity to morphine or methadone.
• Individual has normal cognition defined as normal state of arousal and absence of obvious clinical findings of confusion, memory or concentration deficit.
• Individual has adequate renal function (creatinine less or equal to 2.0 MG/DL)
• Individual has a Zubrod performance status of 3 or lower.
• Individual is willing to sign written informed consent.
• Individual is 18 years of age or older.
• Individual on stable doses(on same dose for at least one week) of nonopioid analgesics including NSAIDS, corticosteroids, gabapentin, pregabalin, or antidepressants prescribed for the purposes of pain control.

You may not qualify if:

• Individual is determined incapable of completing the evaluation forms.
• Individual with clinically evident impaired cognition.
• Patient with MEDD greater than 600.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

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

Pain

Interventions

Morphine; Methadone

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The study sample size is too low for any of the differences or non-differences between the groups to be statistically significant.

Results Point of Contact

• Title: Sriram Yennurajalingam, Palliative Care & Rehabilitation Medicine
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Sriram Yennurajalingam, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: November 14, 2007
• First Posted: November 15, 2007
• Study Start: November 1, 2007
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: April 5, 2016
• Results First Posted: April 5, 2016

Record last verified: 2016-03

Locations

US (1)