Aprepitant Without Steroid in Preventing Chemotherapy-induced Nausea and Vomiting in Patients With Colorectal Cancer

Study Overview
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Brief Summary
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Addition of aprepitant, an NK1 receptor antagonist to a 5-HT3 receptor antagonist and dexamethasone regimen was shown to be effective for prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC). Little is known about the efficacy of aprepitant when used without dexamethasone. Dexamethasone is widely used to prevent both acute and delayed nausea and vomiting induced by chemotherapy. However, multi-period use of dexamethasone could be associated with side effect, such as hyperglycemia, dyspepsia and insomnia. This randomized phase III trial studies antiemetic therapy with aprepitant and tropisetron to see how well they work compared to dexamethasone plus tropisetron in preventing chemotherapy-induced nausea and vomiting in patients with colorectal cancer receiving FOLFOX(oxaliplatin, leuvovorin and 5-fluorouracil) chemotherapy.

Official Title
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Steroid-free Regimen With Aprepitant in Preventing Chemotherapy-induced Nausea and Vomiting in Patients With Colorectal Cancer Receiving FOLFOX Chemotherapy: a Randomized Phase 3 Trial

Conditions
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Chemotherapy-induced Nausea and Vomiting, Colorectal Cancer

Intervention / Treatment
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* Drug: Aprepitant+Tropisetron
* Drug: Dexamethasone+Tropisetron


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of colorectal cancer No prior chemotherapy and scheduled to receive FOLFOX chemotherapy (oxaliplatin,leucovorin and 5-fluorouracil) Age ≥18 years Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2 Laboratory index: Hemoglobin ≥ 90 g/L (No blood transfusion within 14 days), Absolute Neutrophil Count ≥ 1.5×10^9/L, Platelet Count ≥ 75×10^9/L, Serum Bilirubin ≤ 1.5×ULN, ALT and AST ≤ 3.0×ULN (without liver metastases), ALT and AST ≤ 5.0×ULN (with liver metastases), Serum Creatinine ≤ 1×ULN, Endogenous Creatinine Clearance>60ml/min Be able to read, understand and complete the questionnaire and diary Be able to understand the study procedures and sign informed consent. Exclusion Criteria: Treatment with any other study medicine within 4 weeks before enrollment. Nausea or vomiting ≤ 24 hours prior to registration Ongoing emesis due to obstruction of digestive tract Concurrent use of olanzapine, phenothiazine or amifostine Female with pregnancy or lactation Severe cognitive compromise Known history of CNS disease (e.g. brain metastases, seizure disorder) Concurrent abdominal radiotherapy Chronic alcoholism Known hypersensitivity to aprepitant, tropisetron, or dexamethasone. Known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial infarction within the previous six months. History of uncontrolled diabetes mellitus Serious or uncontroled infection Known active HIV, viral hepatitis or tuberculosis infections

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 + Tropisetron | Drug: Aprepitant+Tropisetron<br>* Patients will receive the chemotherapy drugs oxaliplatin,leucovorin and 5-fluorouracil as well as the following antiemetic drugs: aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 and 3) plus Tropisetron (5mg IV of day1)<br>|
| Active Comparator: Control arm<br>Dexamethasone+ Tropisetron | Drug: Dexamethasone+Tropisetron<br>* Patients will receive the chemotherapy drugs oxaliplatin, leucovorin and 5-fluorouracil as well as the following antiemetic drugs: Dexamethasone (10 mg IV on day 1 and 5 mg IV days 2, 3) plus Tropisetron (5mg IV of day1)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response | No emetic episodes and no use of rescue medication | Day 1 to Day 5 after chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nausea score | Nausea scores measured by the Nausea and Vomiting Daily Diary/Questionnaire | Day 1 to Day 5 after chemotherapy | 
| Time to First Vomiting Episode or Use of Rescue Medication |  | Day 1 to Day 5 after chemotherapy | 
| Frequency of rescue medication | Patients were asked to record daily number of extra nausea/vomiting pills taken because they developed nausea/vomiting in the following categories: None, One, Two, More than two in Nausea and Vomiting Daily Diary Questionnaire | Day 1 to Day 5 after chemotherapy | 
| Complete response in the acute phase (0-24 hours) | No emetic episodes and no use of rescue medication in the acute phase (0-24 h) | 0 to 24 hours after chemotherapy | 
| Complete response in the delay phase (25 hours-120 hours) | No emetic episodes and no use of rescue medication in the delay phase | Day 2 to Day 5 (25 hours-120 hours) after chemotherapy |