Anti-emetic Prophylaxis With or Without Dexamethasone

Anti-emetic Prophylaxis Using Fosaprepitant , Tropisetron, and Olanzapine, With or Without Dexamethasone for Anthracycline and Cyclophosphamide Chematherapy: A Multicenter, Randomized, Open-labeled Phase 3 Trial

To evaluate the efficacy and safety of a fosaprepitant, tropisetron, and olanzapine antiemetic regimen, with or without dexamethasone, in patients receiving highly emetogenic chemotherapy with epirubicin and cyclophosphamide.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Nausea and Vomiting
• Intervention / Treatment: Drug: Fosaprepitant, tropisetron, and olanzapine-based antiemetic regimen; Drug: Fosaprepitant, tropisetron, olanzapine, and dexamethasone-based antiemetic regimen

Detailed Description

Patients in this study were randomly assigned in a 1:1 ratio to one of two groups using an interactive response system with permuted blocks of four, stratified by age (<55 vs. ≥55 years). They received either a three-drug antiemetic regimen with fosaprepitant, tropisetron, and olanzapine (triple group) or a four-drug regimen including fosaprepitant, tropisetron, olanzapine, and dexamethasone (quadruple group). All patients were hospitalized for approximately 120 hours post-chemotherapy, documenting emetic episodes, rescue medication use, and nausea ratings on a Likert scale (0 = no nausea, 1 = mild nausea, 2 = moderate nausea, 3 = severe nausea) in a diary. Rescue therapy was available as needed. Clinical staff monitored adverse events every 24 hours using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Subjects who initiated treatment were followed up for endpoints, including complete response (CR), complete control (CC), total control (TC), quality of life, and safety assessments.

• Study Type: Interventional
• Enrollment (Actual): 442
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Henan
    • Henan, Henan, China, 450008
      • Henan cacer hospital
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Breast cancer patients receiving their first anthracycline/cyclophosphamide-based HEC regimen (cyclophosphamide 600 mg/m², epirubicin 90-100 mg/m²); divided doses excluded.
2. No prior chemotherapy.
3. Aged 18-70 years.
4. ECOG performance status 0 or 1.
5. Adequate organ function: (including absolute neutrophil count≥1,500/mm3, WBC count≥3,000/mm3, platelet count≥100,000/mm3, AST< 2.5×the upper limit of normal (ULN), ALT< 2.5×ULN, bilirubin< 1.5×ULN, creatinine< 1.5×ULN).
6. No nausea or vomiting within 24 hours before registration.
7. Negative pregnancy test within 7 days prior (women of childbearing potential).
8. No severe cognitive impairment.
9. No hypersensitivity to fosaprepitant, tropisetron, olanzapine, and dexamethasone.
10. No significant cardiac issues: arrhythmia, recent heart failure, or myocardial infarction within 6 months.
11. No symptomatic brain metastasis or carcinomatous meningitis.
12. No diabetes requiring insulin or oral medication.
13. No use of prohibited medications within 48 hours before registration or during treatment.
14. Informed consent obtained.

Exclusion Criteria:

1. History of allergic reactions to study drugs or their analogues.
2. Nausea and vomiting requiring antiemetic treatment at registration.
3. Pregnant or nursing women, those who may become pregnant, or those not planning to use contraception.
4. Mental illness or psychiatric symptoms interfering with daily activities, making study participation difficult.
5. Diabetes treated with insulin/oral hypoglycemics or HbA1c (NGSP) ≥ 6.5% or HbA1c (JDS) ≥ 6.1% at registration.
6. Recent (within 6 months) unstable angina, myocardial infarction, cerebral hemorrhage, cerebral infarction, or active gastroduodenal ulcer.
7. Convulsive disorders requiring anticonvulsants, ascites needing therapeutic puncture, or gastrointestinal obstruction.
8. Inability to be hospitalized for up to 120 hours (Day 6) post-AC administration initiation.
9. Any other conditions deemed inappropriate for study participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triple group; A three-drug antiemetic regimen with fosaprepitant, tropisetron, and olanzapine (triple group)	Drug: Fosaprepitant, tropisetron, and olanzapine-based antiemetic regimen; Fosaprepitant 150 mg intravenously on Day 1, tropisetron 5 mg intravenously on Day 1, and olanzapine 5 mg orally on Days 1 to 4.; Other Names: Fosaprepitant+Tropisetron+Olanzapine
Active Comparator: Quadruple group; A four-drug regimen including fosaprepitant, tropisetron, olanzapine, and dexamethasone (quadruple group)	Drug: Fosaprepitant, tropisetron, olanzapine, and dexamethasone-based antiemetic regimen; Fosaprepitant 150 mg intravenously on Day 1, tropisetron 5 mg intravenously on Day 1, and olanzapine 5 mg orally on Days 1 to 4. Dexamethasone 12 mg on Day 1, followed by 8 mg on Days 2 to 4.; Other Names: Fosaprepitant+Tropisetron+Olanzapine+Dexamethasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CR) during overall (0-120 hours after the initiation of anthracycline/cyclophosphamide administration) phase.	CR was determined by the absence of any retching or vomiting and the absence of any requirement for additional antiemetic treatment.	0-120 hours after the initiation of anthracycline/cyclophosphamide administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR during the acute (0-24 hours after the initiation of anthracycline/cyclophosphamide administration) and delayed (24-120 hours after the initiation of anthracycline/cyclophosphamide administration) phase	CR was determined by the absence of any retching or vomiting and the absence of any requirement for additional antiemetic treatment.	0-24 hours and 24-120 hours after the initiation of anthracycline/cyclophosphamide administration
Complete control rate (CC) during the acute, delayed, and overall phase	CC is defined as a condition in which a patient does not report more than mild nausea (0 or 1 on a 4-grade categorical scale) (0 = no nausea, 1 = mild nausea, 2 = moderate nausea, 3 = severe nausea).	Day 1 to day 5 after the initiation of anthracycline/cyclophosphamide administration
Total control rate (TC) during the acute, delayed, and overall phases	TC is defined as a condition in which a patient does not report any nausea (0 on a 4-grade categorical scale) (0 = no nausea, 1 = mild nausea, 2 = moderate nausea, 3 = severe nausea).	Day 1 to day 5 after the initiation of anthracycline/cyclophosphamide administration
Safety outcomes	Adverse event incidence rate	Day 1 to day 5 after the initiation of anthracycline/cyclophosphamide administration
Quality of life based on Functional Living Index-Emesis (FLIE) assessment	Quality of life based on Functional Living Index-Emesis (FLIE) assessment in the overall phase (0-120 h).	0-120 hours after the initiation of anthracycline/cyclophosphamide administration
Exploratory endpoints-The time to the treatment failure	The time to the treatment failure (time to first emetic episode or time to first use of rescue medication, whichever occurred first).	0-120 hours after the initiation of anthracycline/cyclophosphamide administration

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Zhenzhen Liu, Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): August 15, 2023
• Study Completion (Actual): August 15, 2023

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 16, 2022

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Nausea; Vomiting; Glucocorticoids; Physiological Effects of Drugs; Olanzapine; Fosaprepitant; Signs and Symptoms, Digestive; Antiemetics; Tropisetron
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Nausea; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Neurokinin-1 Receptor Antagonists; Selective Serotonin Reuptake Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Olanzapine; Aprepitant; Fosaprepitant; Antiemetics; Tropisetron
• Other Study ID Numbers: HELEN-009

Drug and device information, study documents

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