Clinical trial NCT00003687: Treatment for Chronic Pain in Patients With Advanced Cancer
Official title: A Phase III Double-Blind Equivalence Study of Two Different Formulations of Slow-Release Morphine Followed by a Randomization Between Dextromethorphan or Placebo Plus Statex SR for Chronic Cancer Pain Relief in Terminally Ill Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Pain
Precancerous/Nonmalignant Condition
Small Intestine Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
monoclonal gammopathy of undetermined significance
recurrent adult Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
isolated plasmacytoma of bone
extramedullary plasmacytoma
refractory multiple myeloma
Waldenstrom macroglobulinemia
stage III multiple myeloma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
small intestine lymphoma
unspecified adult solid tumor, protocol specific
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
polycythemia vera
chronic idiopathic myelofibrosis
essential thrombocythemia
untreated hairy cell leukemia
progressive hairy cell leukemia, initial treatment
refractory hairy cell leukemia
chronic myelomonocytic leukemia
T-cell large granular lymphocyte leukemia
acute undifferentiated leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
pain
prolymphocytic leukemia
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
primary systemic amyloidosis
non-Hodgkin lymphoma during pregnancy
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
chronic eosinophilic leukemia
chronic neutrophilic leukemia
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
childhood myelodysplastic syndromes
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 87
Sex: ALL
Minimum age (years): 16
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: RATIONALE: Different drug formulations and combinations of drugs may help patients with chronic pain live more comfortably. It is not yet known which regimen is most effective for chronic pain.

PURPOSE: Randomized phase III trial to compare the effectiveness of different morphine formulations with or without dextromethorphan in treating chronic pain in patients who have advanced cancer.

Detailed description: OBJECTIVES:

* Compare the analgesic efficacy of two formulations of morphine (Statex SR versus MS-Contin) in patients requiring morphine for the treatment of chronic cancer pain.
* Compare the effect of these 2 formulations of morphine on the total analgesic consumption, sleep disturbances, sleep and nausea, responses of different types of pain, and toxic effects experienced in the two treatment groups.
* Compare the effect of coadministration of morphine and dextromethorphan versus morphine and placebo on pain control in the respective patient groups (phase B).
* Compare the effect of morphine and dextromethorphan or placebo on total analgesic consumption, sleep disturbances, sleep and nausea, responses of different types of pain, and toxic effects on the two treatment groups (phase B).

OUTLINE: This is a randomized, double-blind, parallel-group, multicenter study. Patients are stratified by stabilization dose (less than 120 mg/day vs greater than 120 mg/day of morphine) and institution in phase A, and neuropathic pain (yes vs no) in phase B.

* Phase A: Patients are randomized to receive oral morphine in one of two formulations (MS Contin or Statex SR) every 12 hours for 7 days.
* Phase B: Eligible patients from phase A who have taken no more than 2 breakthrough doses of analgesic per day in the previous 2 days are re-randomized to receive dose escalated oral dextromethorphan capsules or placebo every 4 hours, and oral morphine tablets every 12 hours for 14 days.
* Phase C: All patients fulfilling entry criteria at the end of phase A or any time during phase B may receive compassionate use morphine tablets for up to 90 days.

Patients complete a pain diary twice each day during treatment.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically proven advanced cancer with chronic pain
* Cancer pain requiring strong opioids having an average pain score of less than 6/10 on the visual analog scale within last 24 hours
* Pain managed by a stable maintenance dose of MS-Contin formulation of morphine for at least 2 days with no more than 2 breakthrough immediate release morphine doses per 24 hours
* Pain that is expected to be controlled by a stable and adequate total daily dose of sustained release morphine for the first 7 days of the study

PATIENT CHARACTERISTICS:

Age:

* 16 and over

Performance status:

* Not specified

Life expectancy:

* At least 2 months

Hematopoietic:

* Not specified

Hepatic:

* SGOT or SGPT no greater than 3 times upper limit of normal (ULN)
* No liver disease

Renal:

* Creatinine no greater than 2 times ULN
* No kidney failure

Pulmonary:

* No clinically significant respiratory depression
* No severe obstructive airway disease

Other:

* Fluent in English or French
* No known hypersensitivity or allergy to study medications or components or other multiple drug allergies
* Normal cognition defined by the Folstein Mini-Mental State Questionnaire (at least 24/30 correct)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* At least 14 days since prior chemotherapy

Endocrine therapy:

* Concurrent steroids allowed

Radiotherapy:

* At least 14 days since prior analgesic radiotherapy

Surgery:

* Not specified

Other:

* At least 3 months since prior investigational agents
* At least 1 month since prior clinical study
* No concurrent analgesics other than morphine
* No other concurrent medications containing dextromethorphan
* Concurrent antidepressant medication allowed
* Concurrent nonsteroidal antiinflammatory drugs allowed
* At least 14 days since prior monoamine oxidase (MAO) inhibitors
* No concurrent MAO inhibitors

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: St. Johns
country: Canada
facility: Newfoundland Cancer Treatment and Research Foundation
state: Newfoundland and Labrador
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Eduardo Bruera, MD
role: STUDY_CHAIR
References:
citation: MacDonald S, Dudgeon DJ, Bruera E, et al.: A phase III double-blind equivalence study of two different formulations of slow-release morphine followed by a randomization between dextromethorphan or placebo plus Statex SR for chronic cancer pain relief in terminally ill patients. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1521, 2002.
citation: Dudgeon DJ, Bruera E, Gagnon B, Watanabe SM, Allan SJ, Warr DG, MacDonald SM, Savage C, Tu D, Pater JL. A phase III randomized, double-blind, placebo-controlled study evaluating dextromethorphan plus slow-release morphine for chronic cancer pain relief in terminally ill patients. J Pain Symptom Manage. 2007 Apr;33(4):365-71. doi: 10.1016/j.jpainsymman.2006.09.017.