Morphine Versus Methadone As First Line Strong Opioid for Cancer Pain

STUDY DRUGS:

MORPHINE is recommended as the first choice of strong pain killers by the World Health
Organization Pain Relief Guidelines.

METHADONE is recommended as the second choice of strong pain killers.

SCREENING TESTS:

Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. The following
tests and procedures will be performed:

- You will be asked about your level of pain.

- You will be asked about any pain killers you are currently taking.

- You will be asked about your history of allergies.

- Blood (about 1 teaspoon) will be drawn to check your kidney function.

STUDY GROUPS:

If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the toss of the coin) to 1 of 2 treatment groups. Group 1 will receive morphine while
on-study. Group 2 will receive methadone. You will have an equal chance of being placed in
either group. Neither you nor any of the study staff will know which study drug you are
receiving. However, if needed for your safety, the study staff and study doctor will be able
to find out which study drug you are receiving.

STUDY DRUG ADMINISTRATION:

If you are in Group 1, you will take 1 morphine capsule every 12 hours with water. If you
are in Group 2, you will take 1 methadone capsule every 12 hours. Morphine and methadone
should be swallowed whole.

You will be given additional capsules in another bottle to take for excessive pain. The
additional capsules should be taken every 2 hours, as needed. If you need 3 or more of these
additional doses in 24 hours, you should contact the study staff.

STUDY VISITS:

You will return to the clinic at the end of Weeks 1, 2, 4, 6, 8, 10 and 12 for
questionnaires about your pain levels, ability to sleep, constipation, other side effects,
and quality-of-life. You will complete 6 questionnaires at the Weeks 1, 2, 6, 10, and 11
visit. You will complete 11 questionnaires at the Weeks 4, 8, and 12 visits. Each
questionnaire will take 1-3 minutes to complete. The visit with the research nurse will last
about 45 minutes to 1 hour. Your study drug supply will also be checked. You also will be
asked about your overall health, non-health care questions, and activity level. At these
visits, you will receive a new prescription for a 2-week supply of the study drug.

PATIENT DIARY:

You will be given a patient diary booklet before you start taking the study drug. You will
be asked to record when you take the study drug, other medications you may be taking, and
any side effects you experience. You will fill out the patient diary once a day. It will
take less than 2 minutes to complete.

For the first week of the treatment, you will be contacted by the research nurse every day
either in person (if you are in the hospital) or by phone to check for pain, side effects,
and the number of pills you have taken.

You are allowed to take other medication, such as medications for constipation, nausea, and
other drugs during the study. All changes in medication for either symptoms or complications
must be recorded by the research nurse at each study visit.

LENGTH OF STUDY:

After the visit at the end of Week 12, you will be off-study. You will be taken off-study
early if your pain gets worse or intolerable side effects occur.

This is an investigational study. Both morphine and methadone are FDA approved and
commercially available. You will not be told which study drug you were receiving. Up to 250
patients will take part in this study. Up to 200 will be enrolled at M. D. Anderson.

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.