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

• Comparison of active treatment vs placebo [ Designated as safety issue: No ]
• Effect of olanzapine on opiod adverse effects [ Designated as safety issue: No ]
• Relationships between endpoints [ Designated as safety issue: No ]

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.

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.

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

• Drug: olanzapine
  Given orally
• Other: placebo
  Given orally

• Active Comparator: Arm I
  Patients receive oral opioid and oral placebo once daily for 4 weeks.
  Intervention: Other: placebo
• Experimental: Arm II
  Patients receive oral opioid and 2.5 mg oral olanzapine once daily for 4 weeks.
  Intervention: Drug: olanzapine
• Experimental: Arm III
  Patients receive oral opioid and 5 mg oral olanzapine once daily for 4 weeks.
  Intervention: Drug: olanzapine

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