Olanzapine for the Treatment of Chronic Nausea and/or Vomiting in Patients With Advanced Cancer

Study Overview
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Brief Summary
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This phase III trial compares olanzapine to placebo in decreasing nausea and vomiting in patients with cancer that has spread to other places in the body (advanced). Patients with advanced cancer may experience nausea and/or vomiting that is unrelated to chemotherapy or radiation. Giving olanzapine may help reduce nausea and increase appetite in patients who have advanced cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. To conduct a confirmatory phase III double-blind randomized clinical trial to evaluate the ability of olanzapine to decrease nausea in patients with advanced-cancer associated nausea/vomiting. SECONDARY OBJECTIVES: I. To evaluate toxicity associated with olanzapine in patients with advanced-cancer associated nausea/vomiting. II. To evaluate the effect of olanzapine on appetite, vomiting, sedation, sleep, the use of other antiemetic agents, fatigue, and well-being. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive olanzapine orally (PO) every night on days 1-28. ARM II: Patients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28.

Official Title
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Olanzapine for the Treatment of Chronic Nausea and/or Vomiting, Unrelated to Chemotherapy or Radiation, in Advanced Cancer Patients - A Confirmatory Phase III MNCCTN Trial

Conditions
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Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm

Intervention / Treatment
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* Drug: Olanzapine
* Drug: Placebo Administration
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years Histologically or cytologically-confirmed cancer in an advanced incurable stage Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 Chronic nausea that has been present for at least one week (daily score > 5, on a 0-10 visual analogue scale) Serum creatinine < 2.0 mg/dl =< 120 days prior to registration Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) values < 3 times upper limits of normal =< 120 days prior to registration Negative pregnancy test done =< 14 days prior to registration, for persons of childbearing potential only Able to provide written informed consent Able to complete questionnaire(s) by themselves or with assistance Exclusion Criteria: Any of the following because this study involves: an agent that has known genotoxic, mutagenic and teratogenic effects: Pregnant persons Nursing persons Received chemotherapy or radiation within the prior 14 days (advanced cancer patients receiving hormonal therapy or targeted therapy that does not come with a recommendation for prophylactic anti-emetic therapy are eligible) Receiving treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone for =< 30 days prior to registration or planned during protocol therapy (patients may have received prochloperazine and other phenothiazines as prior anti-emetic therapy) Those with concurrent use of ethyol; severe cognitive compromise; concurrent use of amifostine; concurrent use of quinolone antibiotic therapy; known hypersensitivity to olanzapine; or have planned chemotherapy or radiation during the 7 days following study initiation Uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection (including human immunodeficiency virus [HIV]) Cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient Psychiatric illness/social situations that would limit compliance with study requirements Inability to swallow oral formulations of the agent(s) Tube feeding or nasogastric tube

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (olanzapine)<br>Patients receive olanzapine PO every night on days 1-28. | Drug: Olanzapine<br>* Given PO<br>* Other names: Zyprexa Zydis;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Arm II (placebo, olanzapine)<br>Patients receive placebo PO every night on days 1-2 and olanzapine PO every night on days 3-28. | Drug: Olanzapine<br>* Given PO<br>* Other names: Zyprexa Zydis;Drug: Placebo Administration<br>* Given PO<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in nausea score | Evaluated using Visual Analogue Scale. Nausea scores at baseline and after the first two days and the change scores, for the first 2 days, will be summarized using mean (standard deviation) and median (range). The change scores from baseline to the end of the first 2 days will be compared between arms using a two-sample t-test or a Wilcoxon rank sum test as appropriate. The difference in nausea change scores from baseline to 2 days post treatment initiation between the two arms will be estimated along with a 95% confidence interval. | Baseline to 24 hours of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily nausea and vomiting scores | Chronic nausea this is present for at least 1 week (worst daily nausea numeric rating scores needed to be greater than 3 on a 0-10 scale). | Up to 28 days | 
| Daily episodes of vomiting/retching (number and time) | Chronic nausea that is present for at least 1 week (worst daily nausea numeric rating scores needed to be greater than 3 on a 0-10 scale). | Up to 28 days | 
| Utilization of rescue therapy | Baseline evaluation that includes assessment of symptom intensity for appetite, nausea, fatigue, sedation, and pain, all measured and recorded on a numeric rating score. (0 indicated the worst possible; 10, best possible). | Up to 28 days | 
| Incidence of adverse events with olanzapine | Measured by patient reported outcome questionnaires and Common Terminology Criteria for Adverse Events version 5.0. | Up to 28 days |