Aprepitant ,Olanzapine,Palonosetron and Dexamethasone for the Prevention of Chemotherapy-induced Nausea and Vomiting

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to mainly evaluate the efficacy and safety of aprepitant in combination with olanzapine ,palonosetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly or moderately emetogenic chemotherapy.

Detailed Description
-----------------
Eligible patients will be randomized to receive different antiemetic regimens . In the experimental group,patients will receive aprepitant,olanzapine ,palonosetron and dexamethasone .In the other group,patients will accept the same dose of aprepitant ,palonosetron and dexamethasone .During the treatment, any grade of nausea and vomiting should be recorded in order to evaluate the complete response rate of CINV,nausea patients will be measured by a visual analogue scale (VAS) ,other adverse events should be recorded as well.

Official Title
-----------------
Aprepitant ,Olanzapine,Palonosetron and Dexamethasone for the Prevention of Chemotherapy-induced Nausea and Vomiting---A Randomized Single Center Phase III Trial

Conditions
-----------------
Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
-----------------
* Drug: Olanzapine
* Drug: Aprepitant
* Drug: Palonosetron
* Drug: Dexamethasone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or older Histologically or cytologically confirmed malignant disease Accept chemotherapy for the first time Patients who will receive high emetogenic cancer chemotherapy (HEC) (cisplatin>=70mg/m2,adriamycin in combination with cyclophosphamide ,cyclophosphamide>=1500mg/m2,adriamycin>60mg/m2,epirubicin>90mg/m2,dacarbazine，ifosfamide>=2g/m2) or moderate emetogenic chemotherapy cancer (carboplatin>=300mg/m2,cyclophosphamide>=600-1000mg/m2,adriamycin>50mg/m2) Written informed consent Exclusion Criteria: Pregnant or breast-feeding Uncontrolled psychosis history Inability or unwillingness to understand or cooperate with study procedures Central nervous system tumors primary or secondary Concurrent abdominal radiotherapy History of uncontrolled diabetes mellitus Patients of prostatic hyperplasia ，paralytic ileus，narrow feet glaucoma. Known cardiac arrhythmia, uncontrolled congestive heart failure ,or acute myocardial infarction with the previous six month Pre-existing nausea or vomiting Inadequate hematological function and abnormal liver and renal function. History of sensitivity to olanzapine Concurrent application of quinolone antibiotic therapy Treatment with another antipsychotic agent such as risperidone,quetiapine, clozapine,phenothiazine,or butyrophenone for 30 days prior to or during the chemotherapy. Cytochrome P450 3A4 substrates within 7 days (terfenadine, cisapride, astemizole, pimozide) Concurrent application of systemic corticosteroids Active infection or gastrointestinal dysfunction

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine regimen<br>Olanzapine in combination with aprepitant ,palonosetron and dexamethasone. | Drug: Olanzapine<br>* 5mg,twice a day orally on day 1 to day 4<br>Drug: Aprepitant<br>* 125 mg capsule per oral, 1 hour before chemotherapy on day 1, 80 mg capsule daily in the morning during days 2 to 3.<br>Drug: Palonosetron<br>* 0.25mg IV 30-60min before chemotherapy on day 1<br>Drug: Dexamethasone<br>* 6mg IV on day 1 ，3.75mg IV on day 2 to 4<br>|
| Other: Control regimen<br>Aprepitant in combination with palonosetron and dexamethasone | Drug: Aprepitant<br>* 125 mg capsule per oral, 1 hour before chemotherapy on day 1, 80 mg capsule daily in the morning during days 2 to 3.<br>Drug: Palonosetron<br>* 0.25mg IV 30-60min before chemotherapy on day 1<br>Drug: Dexamethasone<br>* 6mg IV on day 1 ，3.75mg IV on day 2 to 4<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Receiving HEC With Complete Response in Overall Phase | Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. | 0 to 120 hours | 
| Proportion of Participants Receiving MEC With Complete Response in Overall Phase | Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. | 0 to 120 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Receiving HEC With Complete Response in the Acute Phase | Acute phase was defined as 0 to 24 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. | 0 to 24 hours | 
| Proportion of Participants Receiving HEC With Complete Response in the Delayed Phase | Delayed phase was defined as 24 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. | 24 to 120 hours | 
| Proportion of Participants Receiving HEC With No Vomiting in the Overall Phase | Overall phase was defined as 0 to 120 hours following initiation of chemotherapy. No vomiting was defined as no vomiting or retching or dry heaves (included participants who received rescue therapy). | 0 to 120 hours | 
| Proportion of Participants Receiving HEC With No Vomiting in the Acute Phase | Overall Phase was defined as 0 to 120 hours following initiation of chemotherapy. No vomiting was defined as no vomiting or retching or dry heaves (included participants who received rescue ） | 0 to 24 hours | 
| Proportion of Participants Receiving HEC With No Vomiting in the Delayed Phase | Overall Phase was defined as 24 to 120 hours following initiation of chemotherapy. No vomiting was defined as no vomiting or retching or dry heaves (included participants who received rescue therapy). | 24 to 120 hours | 
| Proportion of Participants Receiving MEC With Complete Response in the Acute Phase | Acute phase was defined as 0 to 24 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. | 0 to 24 hours | 
| Proportion of Participants Receiving MEC With Complete Response in the Delayed Phase | Delayed phase was defined as 24 to 120 hours following initiation of chemotherapy. Complete response was defined as no vomiting with no rescue therapy. | 24 to 120 hours | 
| Proportion of Participants Receiving MEC With No Vomiting in the Overall Phase | Overall Phase was defined as 0 to 120 hours following initiation of chemotherapy. No vomiting was defined as no vomiting or retching or dry heaves (included participants who received rescue therapy). | 0-120 hours | 
| Proportion of Participants Receiving MEC With No Vomiting in the Acute Phase | Overall Phase was defined as 0 to 24 hours following initiation of chemotherapy. No vomiting was defined as no vomiting or retching or dry heaves (included participants who received rescue therapy). | 0 to 24 hours | 
| Proportion of Participants Receiving MEC With No Vomiting in the Delayed Phase | Overall Phase was defined as 24 to 120 hours following initiation of chemotherapy. No vomiting was defined as no vomiting or retching or dry heaves (included participants who received rescue therapy). | 24 to 120 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chemotherapy nausea vomiting