Opioids With or Without Olanzapine in Treating Patients With Moderate to Severe Cancer Pain

Study Overview
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Brief Summary
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RATIONALE: Opioids lessen pain caused by cancer. It is not yet known whether opioids are more effective when given together with or without olanzapine in treating cancer pain. PURPOSE: This randomized clinical trial is studying opioids to see how well they work when given together with or without olanzapine in treating patients with moderate to severe cancer pain.

Detailed Description
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OBJECTIVES: To assess the analgesic effect of olanzapine when administered in combination with opioids in patients with cancer pain. To assess the opiod-sparing effect of olanzapine vs placebo. To assess the effect of olanzapine on opioid adverse effects. OUTLINE: Patients undergo opioid titration with a step 3 opioid to maintain a less than 4/10 level of pain (on a 0-10 numeric pain rating scale) to establish a opioid starting dose. When the pain rating increases, patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive oral opioid and oral placebo once daily for 4 weeks. Arm II: Patients receive oral opioid and 2.5 mg oral olanzapine once daily for 4 weeks. Arm III: Patients receive oral opioid and 5 mg oral olanzapine once daily for 4 weeks. Patients undergo quality of life assessments at baseline and three times weekly by questionnaires using a scale from 0-3 and pain assessments periodically by Brief Pain Inventory, Edmonton Symptom Assessment Scale, Linear Analogue Scale Assessments, and Mini-Mental State Examination.

Official Title
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Analgesic Effect of Olanzapine in Cancer Pain: A Double-Blind Randomized Placebo-Controlled Parallel Group Pilot Study

Conditions
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Hematopoietic/Lymphoid Cancer, Pain, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: olanzapine
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Moderate to severe cancer pain Pain score ≥ 7/10 (0-10 numeric pain rating scale) Requires strong opioids (step 3) for pain control or are already on stable doses of step 3 opioids Opioid induced cognitive dysfunction or cognitive impairment, defined as cognitive disorder not otherwise specified according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) allowed No nonmalignant pain If patient has both malignant and nonmalignant pain, eligibility will be determined by the predominant site of pain PATIENT CHARACTERISTICS: Life expectancy ≥ 3 months Normal renal function Not pregnant or nursing Negative pregnancy test Must have a telephone Able to complete patient questionnaires alone or with assistance No delirium No hepatic dysfunction No nursing home patients No intractable nausea or vomiting No true allergy or intolerance to opioids No gastrointestinal pathology that influences absorption of opioids No drug seeking behavior or recent substance abuse history No major depression No respiratory compromise No evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) No evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study PRIOR CONCURRENT THERAPY: More than 1 month since prior radiotherapy, chemotherapy, or radionuclides More than 1 month since prior bisphosphonates No prior surgery that influences absorption of opioids No concurrent therapeutic procedures or treatments that influence pain No concurrent active radiation or antineoplastic therapies No concurrent retroviral therapies No concurrent drugs that interfere with CYP34A, CYP1A2, or CYP2D6 No concurrent drugs that interfere with morphine metabolism No concurrent medications that will influence the disposition of morphine or methadone No other concurrent antiemetics, antianxiety, or neuroleptic agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive oral opioid and oral placebo once daily for 4 weeks. | Other: placebo<br>* Given orally<br>|
| Experimental: Arm II<br>Patients receive oral opioid and 2.5 mg oral olanzapine once daily for 4 weeks. | Drug: olanzapine<br>* Given orally<br>|
| Experimental: Arm III<br>Patients receive oral opioid and 5 mg oral olanzapine once daily for 4 weeks. | Drug: olanzapine<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Two-point pain improvement from baseline (0-10 numeric pain rating scale) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of active treatment vs placebo |  |  | 
| Effect of olanzapine on opiod adverse effects |  |  | 
| Relationships between endpoints |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific, hematopoietic/lymphoid cancer, pain