Aprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting

Study Overview
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Brief Summary
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To compare the antiemetic combination of palonosetron, dexamethasone, and aprepitant (PDA) with antiemetic combination of palonosetron and dexamethasone (PD) in nasopharyngeal carcinoma patients receiving docetaxel, cisplatin, and 5-FU based chemotherapy.

Detailed Description
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Eligible patients will be randomized to receive different antiemetic regimens . In the experimental group,patients will receive aprepitant, palonosetron and dexamethasone .In the other group,patients will accept the same dose of 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
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Aprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting Following High-dose Cisplatin in Nasopharyngeal Carcinoma Patients：a Randomized Phase 3 Trial

Conditions
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Chemotherapy-induced Nausea and Vomiting

Intervention / Treatment
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* Drug: Aprepitant+palonosetron+dexamethasone
* Drug: palonosetron+dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Histologically or cytologically confirmed nasopharyngeal carcinoma Accept chemotherapy for the first time Patients who will receive chemotherapy (docetaxel 60 mg/m2 intravenously (IV), cisplatin 60 mg/m2 IV, and 5-FU (5-Fluorouracil) 600 mg/m2 IV) Written informed consent Exclusion Criteria: regnant 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
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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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aprepitant arm<br>Aprepitant+palonosetron+dexamethasone | Drug: Aprepitant+palonosetron+dexamethasone<br>* Patients will receive the chemotherapy drugs as well as the following antiemetic drugs: aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 and 3) plus palonosetron 0.25 mg IV and dexamethasone (20 mg orally on day 1 and 8 mg orally on days 2 and 3)<br>* Other names: PDA;|
| Active Comparator: Control arm<br>palonosetron+dexamethasone | Drug: palonosetron+dexamethasone<br>* Patients will receive the chemotherapy drugs as well as the following antiemetic drugs: palonosetron 0.25 mg IV and dexamethasone (12 mg orally on day 1 and 8 mg orally on days 2 and 3)<br>* Other names: PD;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response | The primary endpoint is the rate of patients achieving a complete response(defined as no emetic episode and no use of rescue medication) during over all time (0 to 120 hours post chemotherapy) | Up to 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Phase Response | To determine the effect on complete response(defined as no emetic episode and no use of rescue medication) rates in the acute (0 to 24 hours) phase of CINV. | 0 to 24 hours post chemotherapy | 
| Delayed Phase Response | To determine the effect on complete response (defined as no emetic episode and no use of rescue medication)rates in the delayed (>24 to 120 hours post chemotherapy) phase of CINV. | >24 to 10 days post chemotherapy | 
| Functional Living Index -Emesis (FLIE) |  | Up to 10 days | 
| Safety and tolerability as measured by the incidence and severity of adverse | To evaluate the safety and tolerability by the incidence and severity of adverse events during the treatment (0 to 120 hours post chemotherapy) | Up to 10 days |