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

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

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.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Nausea and Vomiting; Colorectal Cancer
• Intervention / Treatment: Drug: Aprepitant+Tropisetron; Drug: Dexamethasone+Tropisetron

• Study Type: Interventional
• Enrollment (Actual): 315
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Gastrointestinal Hospital, Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Yanhong Deng, M.D., Sun Yat-sen University

Publications and helpful links

General Publications

• Cheng Y, Wu Z, Shi L, Shen C, Zhang J, Hu H, Li W, Cai Y, Xie X, Ling J, Zheng Q, Deng Y. Aprepitant plus palonosetron versus dexamethasone plus palonosetron in preventing chemotherapy-induced nausea and vomiting in patients with moderate-emetogenic chemotherapy: A randomized, open-label, phase 3 trial. EClinicalMedicine. 2022 Jun 3;49:101480. doi: 10.1016/j.eclinm.2022.101480. eCollection 2022 Jul.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): October 23, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: September 19, 2016
• First Submitted That Met QC Criteria: September 19, 2016
• First Posted (Estimate): September 21, 2016

Study Record Updates

• Last Update Posted (Actual): July 29, 2021
• Last Update Submitted That Met QC Criteria: July 24, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Signs and Symptoms, Digestive; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Nausea; Vomiting; Colorectal Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Neurokinin-1 Receptor Antagonists; Dexamethasone; Aprepitant; Tropisetron
• Other Study ID Numbers: GIHSYSU12

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No