Methadone, Morphine, or Oxycodone in Treating Pain in Patients With Cancer

Condition(s) targeted: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Pain; Precancerous/Nonmalignant Condition; Unspecified Adult Solid Tumor, Protocol Specific

Intervention: methadone hydrochloride (Drug); morphine sulfate (Drug); oxycodone hydrochloride (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Michael J. Fisch, MD, MPH, FACP, Study Chair, Affiliation: M.D. Anderson Cancer Center
James D. Bearden, MD, Affiliation: CCOP - Upstate Carolina

RATIONALE: Methadone, morphine, or oxycodone may help relieve pain caused by cancer. It is not yet known whether methadone is more effective than morphine or oxycodone in treating pain in patients with cancer.

PURPOSE: This randomized clinical trial is studying methadone to see how well it works compared with morphine or oxycodone in treating pain in patients with cancer.

Official title: A Randomized Comparison of Oral Methadone as a "First-Switch" Opioid Versus Opioid Switching Between Sustained-Release Morphine and Oxycodone for Oncology-Hematology Outpatients With Pain Management Problems: The "Simply Rotate" Study

Study design: Supportive Care, Randomized, Open Label

Primary outcome: At least a 3-point reduction in pain score on the M.D. Anderson Symptom Inventory (MDASI)

Secondary outcome:

30% reduction in patients' total summary score for the individual composite drug toxicity score (CDTS) items

Identification of a subset of patients most likely to benefit from an opioid rotation to oral methadone, in terms of significant improvement in pain control or opioid tolerability

Detailed description: OBJECTIVES:

Primary

- To compare the effectiveness of an opioid rotation to oral methadone versus an opioid

rotation to another long-acting strong opioid (sustained-release morphine or oxycodone) in controlling pain (i. e., analgesia) in patients with cancer.

Secondary

- To compare the tolerability of an opioid rotation to oral methadone versus an opioid

rotation to another long-acting strong opioid (sustained-release morphine or oxycodone).

- To identify a subset of patients most likely to benefit from an opioid rotation to oral

methadone, in terms of significant improvement in pain control or opioid tolerability.

OUTLINE: This is a multicenter study. Patients are stratified according to their baseline opioid (morphine vs oxycodone). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients are switched from their current opioid medication (oxycodone or

morphine) to methadone. Patients receive oral methadone 2-3 times daily for 4 weeks.

- Arm II: Patients currently receiving oxycodone are switched to sustained-release (SR)

morphine. Patients currently receiving morphine are switched to SR oxycodone. Patients receive either oral SR morphine or oxycodone 2-3 times daily for 4 weeks.

Patients are assessed for pain control and complete a symptom questionnaire on days 1, 8, 15, 22, and 28.

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

Criteria:

DISEASE CHARACTERISTICS:

- Receiving ongoing care in the outpatient medical oncology setting

- Self-reported pain (of any cause) for which long-acting strong opioids (morphine or

oxycodone) have been prescribed or administered

- Oral morphine-equivalent daily dose (MEDD) of existing opioid regimen

(long-acting or immediate-release) 40-300 mg/day

- Worst pain score on a scale of 0 (no pain) to 10 (worst pain) of ≥ 5 for ≥ 1 week

duration based on verbal self-report AND/OR ≥ 1 persistently bothersome symptom attributed to an opioid side effect (e. g., fatigue, confusion, depressed level of consciousness, memory loss, personality change, anorexia, constipation, dehydration, nausea, vomiting, weight loss, pruritus, urticaria, impotence, reduced libido, and urinary retention or hesitancy)

PATIENT CHARACTERISTICS:

- None of the following conditions that could predispose the patient to prolonged QT

interval-associated tachycardia:

- Serum potassium < 3. 0 mg/dL

- Cocaine abuse within the past 3 months

- Family history of sudden death

- Advanced heart failure (ejection fraction < 40% and/or NYHA class III or IV

heart disease)

- No known or suspected cognitive impairment that could interfere with adherence to the

medication plan or self-report of symptoms and side effects

- Not pregnant or nursing

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- More than 4 weeks since prior radiotherapy or surgery for local control of cancer or

pain palliation

- More than 60 days since prior use of the same long-acting opioid (i. e., the new

long-acting opioid) that patient is switching to on the study

- More than 12 weeks since prior methadone therapy

- More than 3 days since prior and no concurrent transdermal fentanyl, oxymorphone, or

buprenorphine

- Concurrent systemic anticancer therapy or bisphosphonates allowed provided therapy

was initiated ≥ 4 weeks ago

- Concurrent tricyclic antidepressants, NSAIDs, anticonvulsants, or other adjuvant

analgesics or psychostimulants allowed provided therapy was initiated ≥ 2 weeks ago

- Dose expected to remain stable until after the first week of opioid rotation on

study

- No concurrent methadone maintenance therapy for opioid addiction

- No concurrent intrathecal infusion of analgesics

- No concurrent antiarrhythmic medications (e. g., amiodarone or quinidine)

Palmetto Hematology Oncology, PC at Gibbs Regional Cancer Center, Spartanburg, South Carolina 29303, United States; Recruiting
James D. Bearden, MD, Phone: 864-560-6812, Email: jbearden@srhs.com

M. D. Anderson Cancer Center at University of Texas, Houston, Texas 77030-4009, United States; Recruiting
Michael J. Fisch, MD, MPH, FACP, Phone: 713-563-0276

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: March 2009
Last updated: June 9, 2009