Clinical trial NCT00726830: Methadone, 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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: 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
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
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-08-01
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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)

Primary outcomes:
measure: Number of Participants With at Least a 3-point Reduction in Pain Score on the M.D. Anderson Symptom Inventory (MDASI)
timeFrame: 28 days
Secondary outcomes:
measure: Number of Participants With 30% Reduction in Total Summary Score for the Individual Composite Drug Toxicity Score (CDTS) Items
timeFrame: 28 days
Other outcomes:
Locations:
city: Spartanburg
country: United States
facility: Palmetto Hematology Oncology, PC at Gibbs Regional Cancer Center
state: South Carolina
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Michael J. Fisch, MD, MPH, FACP
role: STUDY_CHAIR
affiliation: CCOP - Upstate Carolina
name: James D. Bearden, MD
role: STUDY_CHAIR
References: