Olanzapine and 5-HT3 With or Without Dexamethasone to Prevent CINV

Study Overview
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Brief Summary
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Nausea and vomiting caused by chemotherapy are considered by patients as the main side effects of cancer treatment, which affect the quality of treatment and life.At present, NCCN guidelines have recommended three or four drug regimens for highly emetic chemotherapy (HEC) to prevent vomiting, all containing dexamethasone.However, its side effects such as moderate to severe insomnia, hyperglycemia, dyspepsia, upper abdominal discomfort, irritability, increased appetite, weight gain and acne are gathering increasing concerns.For certain patients, the use of dexamethasone should be avoided.Analysis shows that olanzapine can replace the effect of dexamethasone.Hence, the investigators initiated this prospective, multi-center, phase III study to validate the dexamethasone-free protocol: removing dexamethasone from a three drug regimen containing olanzapine, dexamethasone, and 5-HT3RA.

Official Title
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Olanzapine and 5-HT3 With or Without Dexamethasone to Prevent Nausea and Vomiting Induced by Chemotherapy：:A Non-inferiority, Prospective, Multi-Centered, Randomized, Controlled, Phase III Clinical Trial

Conditions
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Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: 5HT3RA+Olanzapine
* Drug: 5HT3RA+Olanzapine+Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age or older with malignant disease； Life expectancy ≥ 3 months; Scheduled to receive highly emetogenic chemotherapy； Had a European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Exclusion Criteria: There are contraindications to chemotherapy(Absolute number of neutrophils ≤ 1,500/uL, hemoglobin ≤ 90g/L, platelet count ≤ 10000/uL, serum creatinine level ≥ 2.0mg/dl (177 μmol/L), ALT and AST ≥ 2.5 times the upper normal limit, bilirubin ≥ 1.5 times the upper normal limit); History of central nervous system disease (e.g., brain metastases or a seizure disorder); Severe cognitive impairment； Treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, a phenothiazine, or a butyrophenone within 30 days before enrollment or plans for such treatment during the study period; Concurrent use of pharyngeal or abdominal radiotherapy; Concurrent use of quinolone antibiotics; Concurrent use of Amifostine; Chronic alcoholism; Known hypersensitivity to olanzapine; Know arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within 6 months; Known uncontrolled diabetes mellitus; Vomiting or retching 24 hours before chemotherapy; Use of anti-emesis drugs 48 hours before chemotherapy; Patients who require medication with dexamethasone for pretreatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5HT3RA+Olanzapine<br>Using one of the 5-HT3 receptor antagonists within 30 minutes before cisplatin/adriamycin/cyclophosphamide.On day 1-4, Olanzapine is delivered orally after dinner. | Drug: 5HT3RA+Olanzapine<br>* Using one of the 5-HT3 receptor antagonists within 30 minutes before cisplatin/adriamycin/cyclophosphamide. On day 1-4, Olanzapine is delivered orally after dinner.<br>|
| Active Comparator: 5HT3RA+Olanzapine+Dexamethasone<br>Using one of the 5-HT3 receptor antagonists within 30 minutes before cisplatin/adriamycin/cyclophosphamide.On day 1-4, Olanzapine is delivered orally after dinner.On first day, dexamethasone is given orally within 30 minutes before cisplatin/adriamycin/cyclophosphamide administered. | Drug: 5HT3RA+Olanzapine+Dexamethasone<br>* Using one of the 5-HT3 receptor antagonists within 30 minutes before cisplatin/adriamycin/cyclophosphamide. On day 1-4, Olanzapine is delivered orally after dinner. On first day, dexamethasone is given orally within 30 minutes before cisplatin/adriamycin/cyclophosphamide administered. Other Names: Acidocont; Deronil; Dexacortal; Desameton; Fluprednisolone; (11β，16α-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 0-120h Complete Remission Rate | The ratio of patients who have no vomiting and apply no anti-nausea drugs during the whole observation period. | 24 hours ,48 hours, 72 hours, 96 hours, 120 hours after chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 25-120 hours Complete Remission Rate | The ratio of patients who have no vomiting and apply no anti-nausea drugs during the 25-120 hours observation period. | 24 hours ,48 hours, 72 hours, 96 hours, 120 hours after chemotherapy | 
| 0-120h No Nausea Rate | The ratio of patients who have no nausea during the whole observation period. | 24 hours, 48 hours, 72 hours, 96 hours, 120 hours after chemotherapy |