Brain and Central Nervous System Tumors, Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Pain, Precancerous Condition, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
pain, unspecified adult solid tumor, protocol specific, accelerated phase chronic myelogenous leukemia, acute undifferentiated leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), atypical chronic myeloid leukemia, BCR-ABL1 negative, blastic phase chronic myelogenous leukemia, chronic myelomonocytic leukemia, chronic phase chronic myelogenous leukemia, mast cell leukemia, meningeal chronic myelogenous leukemia, progressive hairy cell leukemia, initial treatment, prolymphocytic leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent adult T-cell leukemia/lymphoma, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, stage III adult T-cell leukemia/lymphoma, stage III chronic lymphocytic leukemia, stage IV adult T-cell leukemia/lymphoma, stage IV chronic lymphocytic leukemia, T-cell large granular lymphocyte leukemia, untreated adult acute lymphoblastic leukemia, untreated adult acute myeloid leukemia, untreated hairy cell leukemia, adult grade III lymphomatoid granulomatosis, adult nasal type extranodal NK/T-cell lymphoma, AIDS-related diffuse large cell lymphoma, AIDS-related diffuse mixed cell lymphoma, AIDS-related diffuse small cleaved cell lymphoma, AIDS-related immunoblastic large cell lymphoma, AIDS-related peripheral/systemic lymphoma, AIDS-related primary CNS lymphoma, AIDS-related small noncleaved cell lymphoma, AIDS-related lymphoblastic lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, stage III adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult Hodgkin lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage III mycosis fungoides/Sezary syndrome, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage III small lymphocytic lymphoma, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult Hodgkin lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, stage IV mycosis fungoides/Sezary syndrome, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, HIV-associated Hodgkin lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, intraocular lymphoma, primary central nervous system non-Hodgkin lymphoma, primary central nervous system Hodgkin lymphoma, post-transplant lymphoproliferative disorder, chronic eosinophilic leukemia, chronic neutrophilic leukemia, primary myelofibrosis, essential thrombocythemia, polycythemia vera, extramedullary plasmacytoma, isolated plasmacytoma of bone, monoclonal gammopathy of undetermined significance, stage II multiple myeloma, stage III multiple myeloma, primary systemic amyloidosis, refractory multiple myeloma, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable, cutaneous B-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia
Brief summary
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.
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.
Interventions
Given orally
Given orally
DRUGmorphine sulfate
Given orally
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 New York Heart Association (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, Nonsteroidal Antiinflammatory Drugs (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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least a 3-point Reduction in Pain Score on the M.D. Anderson Symptom Inventory (MDASI) | 28 days | MDASI questionnaire completed on days 8, 15, and 22 after enrollment. The 'primary success' is defined as a 3-point reduction in pain score on the MDASI. Scores from baseline and from four weeks later compared using the MDASI average pain intensity on a scale of 0 (no pain) to 10 (worst pain). |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With 30% Reduction in Total Summary Score for the Individual Composite Drug Toxicity Score (CDTS) Items | 28 days |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: March 10, 2009 to October 1, 2010. Recruitment occured within University of Texas MD Anderson Cancer Center and Palmetto Hematology Oncology at Gibbs Regional Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Arm I: Opioid Rotation to Oral Methadone Participants are switched from their current opioid medication (oxycodone or morphine) to methadone. Participants receive oral methadone 2-3 times daily for 4 weeks. | 1 |
| Arm II: Opioid Rotation to Another Long-acting Strong Opioid Participants currently receiving oxycodone are switched to sustained-release (SR) morphine. Participants currently receiving morphine are switched to SR oxycodone. Participants receive either oral SR morphine or oxycodone 2-3 times daily for 4 weeks. | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Arm I: Opioid Rotation to Oral Methadone | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 1 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Number of Participants With at Least a 3-point Reduction in Pain Score on the M.D. Anderson Symptom Inventory (MDASI)
MDASI questionnaire completed on days 8, 15, and 22 after enrollment. The 'primary success' is defined as a 3-point reduction in pain score on the MDASI. Scores from baseline and from four weeks later compared using the MDASI average pain intensity on a scale of 0 (no pain) to 10 (worst pain).
Time frame: 28 days
Population: No Analysis accomplished as there is not sufficient participant data to meet the study end points.
Secondary
Number of Participants With 30% Reduction in Total Summary Score for the Individual Composite Drug Toxicity Score (CDTS) Items
Time frame: 28 days