Morphine Versus Methadone As First Line Strong Opioid for Cancer Pain

• Status: Terminated
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Analgesics, Opioid; Methadone; Morphine

Criteria

Inclusion Criteria:

1. Patient has pain caused by advanced cancer (local recurrence or metastatic disease)

2. 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).

3. Patient is receiving mild opioids (e.g. propoxyphene, codeine, tramadol, hydrocodone), mixed agonist/antagonist (e.g. buprenorphine) or no opioids.

4. Patient requires initiation of strong opioid for cancer pain.

5. Patient has the ability to receive morphine or methadone orally.

6. 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).

7. Patient has normal cognition defined as normal state of arousal and absence of obvious clinical findings of confusion, memory or concentration deficit.

8. Patient has normal renal function (creatinine and blood urea nitrogen (BUN) within normal limits)

9. Patient's performance status (ECOG) is 3 or less.

10. Patient is willing to sign written informed consent.

11. Patient is 18 years of age or older.

12. 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:

1. 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.

2. Patient is receiving radiation therapy for pain control.

3. 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,).

4. Patients are determined incapable of completing the evaluation forms.

5. Severe hypotension, acute or severe asthma, paralytic ileus, gastrointestinal obstruction, severe respiratory depression.