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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Completed

CT.gov ID

NCT02909478

Collaborator

(none)

315

Enrollment

Location

Arms

Actual Duration (Months)

11.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapy-induced Nausea and Vomiting Colorectal Cancer	Drug: Aprepitant+Tropisetron Drug: Dexamethasone+Tropisetron	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

315 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Sep 1, 2017

Actual Primary Completion Date :

Oct 23, 2019

Actual Study Completion Date :

Dec 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aprepitant arm Aprepitant + Tropisetron	Drug: Aprepitant+Tropisetron 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)
Active Comparator: Control arm Dexamethasone+ Tropisetron	Drug: Dexamethasone+Tropisetron 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)

Arm

Intervention/Treatment

Experimental: Aprepitant arm

Aprepitant + Tropisetron

Drug: Aprepitant+Tropisetron

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)

Active Comparator: Control arm

Dexamethasone+ Tropisetron

Drug: Dexamethasone+Tropisetron

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)

Outcome Measures

Primary Outcome Measures

Complete response [Day 1 to Day 5 after chemotherapy]
No emetic episodes and no use of rescue medication

Secondary Outcome Measures

Nausea score [Day 1 to Day 5 after chemotherapy]
Nausea scores measured by the Nausea and Vomiting Daily Diary/Questionnaire
Time to First Vomiting Episode or Use of Rescue Medication [Day 1 to Day 5 after chemotherapy]
Frequency of rescue medication [Day 1 to Day 5 after chemotherapy]
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
Complete response in the acute phase (0-24 hours) [0 to 24 hours after chemotherapy]
No emetic episodes and no use of rescue medication in the acute phase (0-24 h)
Complete response in the delay phase (25 hours-120 hours) [Day 2 to Day 5 (25 hours-120 hours) after chemotherapy]
No emetic episodes and no use of rescue medication in the delay phase

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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