Olanzapine or Dexamethasone, With 5-HT3 RA and NK-1 RA, to Prevent CINV

Study Overview
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Brief Summary
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Chemotherapy-induced nausea and vomiting is a common side effect of cancer treatments, and dexamethasone offers a clear advantage over placebo for protection against chemotherapy-induced emesis in both acute and delayed phases. 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. Several clinical trials have shown that olanzapine plays an important role in treating delayed, refractory, breakthrough nausea and vomiting. Its side effects mainly include sedation and weight gaining. At present, the NCCN guidelines have recommended olanzapine-containing three-drug regimen for Highly Emetogenic Chemotherapy (HEC) and moderate emetic chemotherapy (MEC) to prevent vomiting, but its data in the Chinese population is limited. Hence, we initiated this prospective, multi-center, phase III study to validate the dexamethasone-free protocol: applying olanzapine to prevent CINV instead of dexamethasone.

Official Title
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Olanzapine or Dexamethasone, With 5-HT3 RA and NK-1 RA, to Prevent Nausea and Vomiting Induced by Cisplatin-Based Doublet 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: Olanzapine+NK-1 RA+5-HT3 RA
* Drug: Dexamethasone+NK-1 RA+5-HT3 RA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Patients are eligible to be included in the study only if they meet all of the following criteria): Cancer patients, age ≥ 18 years and ≤75 years, ECOG score 0-2 points, receiving cisplatin-containing doublet chemotherapy such as cisplatin + gemcitabine / albumin paclitaxel / etoposide /fluorouracil / irinotecan / temozolomide as first line treatment; Life expectancy ≥ 3 months; Leucocytes≥3,000/uL; AST≤2.5 × upper limit of normal; Bilirubin ≤1.5 × upper limit of normal; Serum creatinine ≤ 1.5 × upper limit of normal. Exclusion Criteria (Patients will be excluded if any of the following criteria is met): History of CNS disease, such as brain metastases or epilepsy; Use of other antipsychotic drugs (such as risperidone, quetiapine, clozapine, phenothiazine, or butyrophenone, or such treatment is under scheduling during the study) within 30 days before enrollment; long-term use of phenothiazine as an antipsychotic agent; Concurrent use of pharyngeal or abdominal radiotherapy; Concurrent use of quinolone antibiotics; 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; Concurrent use of amifostine; Concurrent use of corticosteroids and the only anti-allergic choice is corticosteroids

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Olanzapine+NK-1 RA+5-HT3 RA<br>Using one of the 5-HT3 receptor antagonists (a. Palonosetron: 0.25 mg d1 intravenous; b. Granisetron: 1 mg d1 intravenously, or 2 mg d1 orally; c. Ondansetron: 8-16 mg d1 intravenous or oral. the specific agent is chosen by the primary clinician, and is only delivered on the first day) within 30 minutes before cisplatin. Using one of the NK-1 receptor antagonists(a. Aprepitant: 125 mg orally, d1, 80 mg orally, d2-3; b. Fosaprepitant: 150 mg intravenously, d1) within 1 hour before cisplatin. On day 1-4, Olanzapine (5mg) is delivered orally after dinner. | Drug: Olanzapine+NK-1 RA+5-HT3 RA<br>* On day 1-4, Olanzapine (5mg) is delivered orally after dinner.<br>|
| Active Comparator: Dexamethasone+NK-1 RA+5-HT3 RA<br>Using one of the 5-HT3 receptor antagonists (a. Palonosetron: 0.25 mg d1 intravenous; b. Granisetron: 1 mg d1 intravenously, or 2 mg d1 orally; c. Ondansetron: 8-16 mg d1 intravenous or oral. the specific agent is chosen by the primary clinician, and is only delivered on the first day) within 30 minutes before cisplatin. Using one of the NK-1 receptor antagonists (a. Aprepitant: 125 mg orally, d1, 80 mg orally, d2-3; b. Fosaprepitant: 150 mg intravenously, d1) within 1 hour before cisplatin. On first day, dexamethasone (12 mg) is given orally/intravenously within 30 minutes before cisplatin administered, and on day 2-4, the given dose of dexamethasone is 8 mg. | Drug: Dexamethasone+NK-1 RA+5-HT3 RA<br>* On first day, dexamethasone (12 mg) is given orally/intravenously within 30 minutes before cisplatin administrated, and on day 2-4, the given dose of dexamethasone is 8 mg.<br>* Other names: (11β，16α）-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione;|

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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nausea, vomiting, antiemesis