Role of Methadone As Co-Opioid Analgesic

Condition(s) targeted: Pain

Intervention: Morphine (Drug); Methadone (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Sriram Yennurajalingam, MD, Principal Investigator, Affiliation: U.T.M.D. Anderson Cancer Center

Overall contact:
Sriram Yennurajalingam, MD, Phone: 713-792-6085

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).

Official title: Role of Methadone As Co-Opioid Analgesic in Cancer Patients

Study design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To study whether participants taking low-dose methadone plus morphine have a lower pain score and experience fewer side effects as participants taking morphine only.

Detailed description: The Study Drugs:

Methadone and morphine are both designed to block pain receptors (cells that are sensitive to particular drugs) in your nerves and brain.

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.

- You will be asked about the type of cancer you have.

- You will be asked questions about your symptoms, side effects, and any changes in the

medications you may be taking.

- You will complete 4 questionnaires about any side effects you may be having. They will

take about 30 minutes to complete.

- You will have blood (about 1 teaspoon) drawn to check your kidney function.

- You will have tests to see how sensitive your skin is. These tests involve putting

pressure on the skin over the muscles below your thumb on the palm of your hand.

Study Groups and Study Drug Administration:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in toss of a coin) to 1 of 2 groups. Participants in Group 1 will stay on morphine only. Participants in Group 2 will receive morphine plus methadone. You will have an equal chance (50/50) of being placed in either of the 2 groups. You, the medical staff, and study researchers will not know which group you have been assigned to. If necessary, your doctor will be able to find out what group you are in the event of an emergency.

Participants in Group 1 will take 2 doses of "slow-release" morphine by mouth every 12 hours, every day for 15 days (plus or minus 3 days). You will also have access to "immediate-release" morphine to be used, as needed, for pain. If you need more than 3 of these immediate-release doses in a 24-hour period, you should call your study doctor.

Participants in Group 2 will take 1 dose of slow-release morphine and 1 dose of methadone by mouth every 12 hours, every day for 15 days (plus or minus 3 days). You will also have access to immediate-release morphine to be used, as needed, for pain. If you need more than 3 of these immediate-release doses in a 24-hour period, you should call your study doctor.

You will complete a questionnaire once daily about symptoms and pain you may be experiencing. It will take about 5 minutes to complete each time.

You will be provided with a drug diary to write down when and how often you take pain medication.

Study Visits:

On Days 8 and 15 (plus or minus 3 days) the following test and procedures will be performed:

- You will complete 3 questionnaires about any side effects you may be having. They will

take about 15-20 minutes to complete.

- You will have tests to see how sensitive your skin is.

On Day 15 only (plus or minus 3 days), you will have blood (about 1 teaspoon) drawn to measure kidney function.

Length of Study:

You will be off-study after Day 15 (plus or minus 3 days). You will be taken off study early if the disease gets worse or intolerable side effects occur.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

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

2. Individual is receiving strong opioids (morphine, fentanyl, oxycodone, hydromorphone) for 3 weeks prior to enrollment.

3. 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.

4. Individual has the ability to receive morphine or methadone orally.

5. Individual has no known allergy of history of severe toxicity to morphine or methadone.

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

7. Individual has adequate renal function (creatinine less or equal to 2. 0 MG/DL)

8. Individual has a Zubrod performance status of 3 or lower.

9. Individual is willing to sign written informed consent.

10. Individual is 18 years of age or older.

11. 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.

Exclusion Criteria:

1. Individual is determined incapable of completing the evaluation forms.

2. Individual with clinically evident impaired cognition.

Sriram Yennurajalingam, MD, Phone: 713-792-6085

U.T.M.D. Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Sriram Yennurajalingam, MD, Principal Investigator

The University of Texas M.D.Anderson Cancer Center

Starting date: November 2007
Last updated: September 8, 2009