Fosaprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Patients

Efficacy, Safety and Feasibility of Fosaprepitant for the Prevention of Chemotherapy-induced Nausea and Vomiting in Pediatric Patients With Solid Tumors Receiving Moderately and Highly Emetogenic Chemotherapy

The purpose is to evaluate the effectiveness and safety of fosaprepitant plus ondansetron with dexamethasone or placebo plus ondansetron with dexamethasone in preventing chemotherapy-induced nausea and vomiting (CINV) with MEC/HE multi-day chemotherapy in children with solid tumors.

Study Overview

• Status: Completed
• Conditions: Pediatric Cancer
• Intervention / Treatment: Drug: placebo ondansetron with dexamethasone; Drug: Fosaprepitant,ondansetron, dexamethasone

Detailed Description

Participants will randomly assigned 1:1 to receive double-blind study drug ( fosaprepitant plus ondansetron with dexamethasone OR placebo to fosaprepitant plus ondansetron with dexamethasone). Fosaprepitant or placebo to fosaprepitant were supplied and administered in a blinded manner.

Experimental:

Participants received a single dose of fosaprepitant (age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron (weight based) IV with dexamethasone (weight based) iv/po prior to chemotherapy and up to 72 hours after chemotherapy.

Placebo Comparator:

Participants received a single dose of matched placebo for fosaprepitant administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron (weight based) IV with dexamethasone (weight based) iv/po prior to chemotherapy and up to 72 hours after chemotherapy.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Is 6 months to 17 years of age at time of randomization;
2. Participants with solid tumors receiving multi -day chemotherapy associated with moderate or high risk of emetogenicity;
3. Has a preexisting functional central venous catheter available for study drug administration;
4. PS score ≤ 2 points;
5. Has a predicted life expectancy ≥3 months or weight greater than 6Kg;
6. Patient's parent or guardian signs informed consent.

Exclusion Criteria:

1. Has vomited in the 24 hours prior to chemotherapy initiation on Treatment Day 1;
2. Has a symptomatic primary or metastatic central nervous system (CNS) malignancy with nausea and/or vomiting (asymptomatic participants may participate in study);
3. Will be receiving stem cell rescue therapy in conjunction with study-related course of emetogenic chemotherapy or during the 14 days following administration of fosaprepitant/placebo for fosaprepitant;
4. Has received or will receive total body irradiation of radiation therapy to the abdomen or pelvis in the week prior to Treatment Day 1 and/or during the diary reporting period (120 hours following initiation of chemotherapy);
5. Has had benzodiazepine, opioid or opioid like therapy initiated within 48 hours prior to study drug administration, or is expected to receive within 120 hours following initiation of chemotherapy except for single doses of midazolam, temazepam or triazolam;
6. Has started on systemic corticosteroid therapy within 72 hours prior to study drug administration or is expected to receive a corticosteroid as part of the chemotherapy regimen
7. Is currently taking, or has taken within 48 hours of Treatment Day 1 the following drugs with antiemetic properties: 5-hydroxytryptamine 3 (5-HT3) antagonists (e.g., ondansetron), benzamides (e.g., haloperidol), cyclizine, domperidone, herbal therapies with potential antiemetic properties, olanzapine, phenothiazines (e.g., prochlorpenzine), scopolamine (this is not an exhaustive list);
8. Is currently a user of any recreational or illicit drugs (including marijuana) or has current evidence of drug or alcohol abuse or dependence;
9. Is mentally incapacitated or has a significant emotional or psychiatric disorder;
10. Is allergic to fosaprepitant, aprepitant (MK-0869), ondansetron, or any other 5-HT3 antagonist;
11. Has a known history of QT prolongation or is taking any medication that is known to lead to QT prolongation;
12. Has an active infection (e.g., pneumonia), congestive heart failure, bradyarrhythmia, any uncontrolled disease (e.g., diabetic ketoacidosis, gastrointestinal obstruction) except for malignancy;
13. Has ever participated in a previous study of aprepitant or fosaprepitant or has taken an investigational drug with the last 4 weeks;
14. Abnormal liver function (alanine aminotransferase or aspartate aminotransferase ≥ 2 times higher than the upper bound of the normal value) or abnormal renal function (serum creatinine ≥ 2.5 times higher than the upper bound of the normal value);
15. Has participated in a preliminary study of Aprepitant or Fosapretan, or took the study drug in the past 4 weeks;
16. Other situations that the researcher thinks cannot be included.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: a single dose of fosaprepitant; Participants received a single dose of fosaprepitant (age-based adjustment) administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron (weight based) IV with dexamethasone (weight based) iv/po prior to chemotherapy and up to 72 hours after chemotherapy.	Drug: Fosaprepitant,ondansetron, dexamethasone; Participants will randomly assigned 1:1 to receive double-blind study drug ( fosaprepitant plus ondansetron with dexamethasone OR placebo plus ondansetron with dexamethasone). Fosaprepitant or placebo to fosaprepitant were supplied and administered in a blinded manner.; Other Names: ondansetron, dexamethasone
Placebo Comparator: a single dose of matched placebo; Participants received a single dose of matched placebo for fosaprepitant administered intravenously (IV) on Day 1 prior to chemotherapy plus ondansetron (weight based) IV with dexamethasone (weight based) iv/po prior to chemotherapy and up to 72 hours after chemotherapy.	Drug: placebo ondansetron with dexamethasone; placebo plus ondansetron with dexamethasone; Other Names: ondansetron, dexamethasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR rate	Percentage of participants who experienced a complete response (CR; no vomiting/rescue medication) rate in overall phases.	between 0 and 120 hours after the start of chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CR rate in acute phase	Complete response rate in acute phase	0 to 24 Hours Post Initiation of Chemotherapy
CR rate in delayed phase	Complete response rate in delayed phase	25 to 120 Hours Post Initiation of Chemotherapy

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Yizhuo Zhang, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Actual): June 22, 2023
• Study Completion (Actual): June 22, 2023

Study Registration Dates

• First Submitted: August 9, 2020
• First Submitted That Met QC Criteria: August 10, 2020
• First Posted (Actual): August 11, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 7, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Serotonin 5-HT3 Receptor Antagonists; Antipruritics; Neurokinin-1 Receptor Antagonists; Dexamethasone; Dexamethasone acetate; BB 1101; Ondansetron; Aprepitant; Fosaprepitant
• Other Study ID Numbers: SunYat-senU-fosaprepitant

Drug and device information, study documents

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