Clinical trial NCT05242874: Anti-emetic Prophylaxis With or Without Dexamethasone
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-induced Nausea and Vomiting
Keywords: Nausea
Vomiting
Glucocorticoids
Olanzapine
Tropisetron
Fosaprepitant
Signs and Symptoms, Digestive
Antiemetics
Physiological Effects of Drugs
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2022-02-16
Enrollment: 442
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Complete response rate (CR) during overall (0-120 hours after the initiation of anthracycline/cyclophosphamide administration) phase.
timeFrame: 0-120 hours after the initiation of anthracycline/cyclophosphamide administration
Secondary outcomes:
measure: 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
timeFrame: 0-24 hours and 24-120 hours after the initiation of anthracycline/cyclophosphamide administration
measure: Complete control rate (CC) during the acute, delayed, and overall phase
timeFrame: Day 1 to day 5 after the initiation of anthracycline/cyclophosphamide administration
measure: Total control rate (TC) during the acute, delayed, and overall phases
timeFrame: Day 1 to day 5 after the initiation of anthracycline/cyclophosphamide administration
measure: Safety outcomes
timeFrame: Day 1 to day 5 after the initiation of anthracycline/cyclophosphamide administration
measure: Quality of life based on Functional Living Index-Emesis (FLIE) assessment
timeFrame: 0-120 hours after the initiation of anthracycline/cyclophosphamide administration
measure: Exploratory endpoints-The time to the treatment failure
timeFrame: 0-120 hours after the initiation of anthracycline/cyclophosphamide administration
Other outcomes:
Locations:
city: Henan
country: China
facility: Henan cacer hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan cancer hospital
state: Henan
Study officials:
affiliation: Henan Cancer Hospital
name: Zhenzhen Liu
role: PRINCIPAL_INVESTIGATOR
References: