Morphine Versus Methadone As First Line Strong Opioid for Cancer Pain
Condition: Advanced Cancer; Solid Tumors
MeSH terms: Cancer Pain
Intervention: Morphine; Methadone
Intervention description: 15 mg oral every 12 Hours; additional capsules taken every 2 hours as needed.; 5 mg orally every 12 hours; additional capsules every 2 hours as needed.
Intervention MeSH terms: Morphine; Methadone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Cancer; Solid Tumors; Cancer Pain; Opioid Pain Killer; Morphine; Methadone

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.
    

Eligibility 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) </= 4 weeks of study entry.

          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.