Study With IV NEPA (Fosnetupitant/Palonosetron) for the Prevention of Chemotherapy-induced Nausea and Vomiting in Paediatric Cancer Patients Undergoing Highly Emetogenic Chemotherapy (HEC)

NCT06904235 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: NEPA-22-012024-514321-39
• Study Type: interventional
• Target: 95
• Locations: 4 countries
• Sites: 20

Brief Summary

Chemotherapy often causes nausea and vomiting (CINV), and this is a major problem for the children being treated for cancer. To prevent this, a combination of two substances in fixed proportion (IV NEPA) was developed. The two substances are: palonosetron, an antagonist of 5 HT3 receptors, and fosnetupitant, an antagonist of NK1 receptors that transforms into netupitant in the body. The medication is administered through intravenous injection (IV- drip). This study is built from 2 parts: Part 1: phase 2, open label Part 2: phase 3 double blind The detailed description, study design, study milestones and eligibility criteria will reflect the Part 1 requirements

Conditions

Nausea and Vomiting Chemotherapy-Induced; Nausea Post Chemotherapy

Keywords

Prevention of chemotherapy-induced nausea and vomiting; highly emetogenic chemotherapy; HEC; IV NEPA; CINV

Outcome Measures

Primary Outcomes (3)

• COHORT 1 Neptupitant exposure parameter

  Maximum concentration (Cmax)

  From time zero ( start of IV NEPA infusion) to maximum 168 hours

• COHORT 1 Neptupitant exposure

  Area under the plasma concentration-time curve

  From time zero ( start of IV NEPA infusion) to maximum 168 hours

• COHORT 2 monitoring of AEs (safety and tolerability of IV NEPA)

  monitoring of AEs following repeated IV NEPA administration

  Up to 31 days

Secondary Outcomes (14)

• COHORT 1: To assess the PK profile of netupitant.

  From Time zero ( start of IV NEPA infusion) until 168 hours

• COHORT 1: To assess the PK profile of fosnetupitant.

  From Time zero ( start of IV NEPA infusion) until 168 hours

• COHORT 1: To assess the PK profile palonosetron.

  From Time zero ( start of IV NEPA infusion) until 168 hours

• COHORT 1: To assess the PK profile of netupitant

  From Time zero ( start of IV NEPA infusion) until 48 hours

• COHORT 1: To assess the PK profile of fosnetupitant.

  From Time zero ( start of IV NEPA infusion) until 48 hours

Study Arms (2)

IV NEPA

EXPERIMENTAL

The Test Treatment (IV NEPA) is planned to be administered in Cohort 1 and Cohort 2. IV NEPA Dosing Schedule * Cohort 1 (single-day HEC): Single 30-min infusion on Day 1, before start of chemotherapy. * Cohort 2 (multi-day HEC): Single 30-min infusion on Days 1, 3, and 5 (administration on Day 5 depending on the patient's multi day HEC scheme), before start of chemotherapy or in the morning if no chemotherapy is administered on the same day.

Drug: IV NEPA (fosnetupitant/palonosetron)

Reference Treatment

ACTIVE COMPARATOR

The Reference Treatment is planned to be administered in Cohort 1 only. The Reference Treatment includes fosaprepitant powder for solution for IV infusion and ondansetron liquid solution for IV infusion.

Drug: Reference Treatment: IV ondansetron infusion; Drug: Reference Treatment: IV fosaprepitant infusion

Interventions

IV NEPA (fosnetupitant/palonosetron) DRUG

In NEPA-22-01, different body weight-based dosages of IV NEPA will be applied to patients below and over 3 months of age: Formulation A (for patients ≥3 months of age; 235 mg fosnetupitant/1.5 mg palonosetron per vial) or Formulation B (for patients \<3 months of age; 235 mg fosnetupitant/2.5 mg palonosetron per vial).

IV NEPA

Reference Treatment: IV ondansetron infusion DRUG

IV Ondansetron Dosing Regimen * Day 1 (before start of chemotherapy): One 30-min infusion of 0.15 mg/kg (ondansetron maximum dose: 8 mg per administration) * Day 1 at 4 h and 8 h after the end of first administration: Two 30-min infusions of 0.15 mg/kg (ondansetron maximum dose: 8 mg per administration)

Reference Treatment

Reference Treatment: IV fosaprepitant infusion DRUG

Fosaprepitant IV Dosing Regimen * Patients aged 12 years to \<18 years: a single dose of IV fosaprepitant 150 mg * Patients aged 2 years to \<12 years: a single dose of IV fosaprepitant 4 mg/kg (maximum dose: 150 mg) * Patients aged 6 months to \<2 years: a single dose of IV fosaprepitant 5 mg/kg (maximum dose: 150 mg)

Reference Treatment

Eligibility Criteria

• Age: 0 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Signed written Informed Consent Form (ICF) by parent(s)/legal guardian of the paediatric patient in compliance with the local laws and regulations. In addition, the signed children's Assent Form according to local requirements.
• Male or female in- or out-patient from 0 months (newborns) to \<18 years on the date of enrolment (Day 1).
• Cohort 1: Patient \< 6 months weighing at least 4 kg or patient ≥ 6 months weighing at least 6 kg.
• Cohort 2: Patient weighing at least 4 kg.
• Patient with a predicted life expectancy ≥3 months according to Investigator's opinion.
• Patient naïve or non-naïve to chemotherapy, with histologically and/or cytologically (or imaging in the case of brain tumours and nephroblastomas) confirmed malignant disease.
• Cohort 1: Patient scheduled and eligible to receive at least 1 cycle of single-day HEC.
• Cohort 2: Patient scheduled and eligible to receive at least 1 cycle of multi-day HEC.
• (For the level of emetogenicity of the chemotherapeutic agents, refer to the POGO January 2021 guideline).
• For patients aged ≥10 years: Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2.
• For patient with known hepatic impairment: the patient may be enrolled provided the serum ALT and AST are ≤2.5 ULN, the total bilirubin is ≤1.5 ULN, and in the Investigator's opinion the impairment is not expected to jeopardize the patient's safety during the study.
• For patient with known renal impairment: the patient may be enrolled provided the estimated glomerular filtration rate (eGFR) is ≥70 mL/min/1.73m2 (≥50 mL/min/1.73m2 for children \<3 months old) (the eGFR should be calculated using the modified Schwartz equation) and in the Investigator's opinion the impairment is not expected to jeopardize the patient's safety during the study.
• For patient with known history or predisposition to cardiac abnormalities: as per the Investigator's opinion, the history/predisposition should not jeopardize patient's safety during the study.
• Patient with non-clinically significant abnormal laboratory values or with clinically relevant abnormal laboratory values may be enrolled if in the Investigator's opinion the patient's safety is not expected to be jeopardized.
• Female patient shall: a) not have attained menarche yet or b) have attained menarche and have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at Day 1.

You may not qualify if:

• The patient and/or parent(s)/legal guardian are expected by the Investigator to be non compliant with the study procedures.
• Patient has received or is scheduled to receive total body irradiation; total nodal irradiation; upper abdomen radiotherapy; half or upper body irradiation; or radiotherapy of the cranium, craniospinal regions, head and neck, lower thorax region, or the pelvis within 1 week prior to study entry (Day 1) or within 120 h after start of chemotherapy on Day 1 (Cohort 1 patients) or within 168 h (for Cohort 2 patients receiving the last IV NEPA on Day 3) or 216 h (for Cohort 2 patients receiving the last IV NEPA on Day 5) from start of chemotherapy on Day 1.
• Known history of allergy to any component of the study treatments or other contraindications to any NK1-RAs or 5-HT3-RAs.
• Active infection.
• Any illness or condition that, in the opinion of the Investigator, may pose unwarranted risks in administering the investigational product to the patient.
• Uncontrolled medical condition (e.g., uncontrolled insulin-dependent diabetes mellitus).
• Patient experiencing ongoing vomiting from any organic aetiology (including patients with history of gastric outlet obstruction or intestinal obstruction due to adhesions or volvulus), or patient with hydrocephalus.
• Patient who experienced any vomiting, retching, or nausea within 24 h prior to the administration of the study treatment on Day 1 (Note: functional vomiting for infants, which is normally seen during the first 3 months of life, is not to be considered as vomiting).
• Patient who received any drug with potential antiemetic effect within 24 h prior to administration of study treatment on Day 1, including but not limited to the following:
• NK1-RAs (e.g., (fos)aprepitant or any other drug of this class)
• HT3-RAs (e.g., ondansetron, granisetron, dolasetron, tropisetron, ramosetron)
• Benzamides (e.g., metoclopramide, alizapride)
• Phenothiazines (e.g., prochlorperazine, promethazine, perphenazine, fluphenazine, chlorpromazine, thiethylperazine)
• Benzodiazepines initiated 48 h prior to study treatment administration on Day 1 or expected to be administered within the efficacy assessment period, except for single doses of midazolam, temazepam, or triazolam
• Butyrophenones (e.g., droperidol, haloperidol)

Sponsors & Collaborators

• Helsinn Healthcare SA: lead

Study Sites (20)

Aghia Sophia Children's Hospital, Pediatric Hematology/ Oncology Unit (POHemU)

Athens, Greece

RECRUITING

"AHEPA" University General Hospital of Thessaloniki, 2nd Department of Pediatrics

Thessaloniki, Greece

RECRUITING

Department of Pediatrics, Oncology and Hematology University Children's Clinical Hospital them. Ludwik Zamenhof in Bialystok

Bialystok, Poland

WITHDRAWN

Department of Paediatrics, Haematology, Oncology and Rheumatology Voivodship Children's Hospital them. J. Brudziński

Bydgoszcz, 85-667, Poland

NOT YET RECRUITING

Clinic of Pediatrics, Oncology and Hematology University Pediatric Center them M. Konopnicka SP ZOZ Central Clinical Hospital Medical University of Lodz

Lodz, Poland

RECRUITING

University Children'S Hospital in Lublin, Department of Pediatric Hematology, Oncology, and Transplantology

Lublin, 20-093, Poland

NOT YET RECRUITING

Clinical Department of Paediatric Oncology and Haematology VOIVODSHIP SPECIALIST CHILDREN'S HOSPITAL them. prof. dr. Stanisław Popowski in Olsztyn

Olsztyn, Poland

WITHDRAWN

Department of Pediatric Oncology, Hematology and Transplantation Clinical Hospital them. Karol Jonscher Medical University them. Karol Marcinkowski in Poznań

Poznan, Poland

RECRUITING

Department of Paediatrics and Paediatric Haemato-Oncology University Clinical Hospital No. 1 them. prof. Tadeusz Sokołowski Pomeranian Medical University

Szczecin, Poland

WITHDRAWN

Department of Paediatrics, Oncology and Paediatric Immunology, University Clinical Hospital No. 1 them. prof. Tadeusz Sokołowski Pomeranian Medical University in Szczecin

Szczecin, Poland

RECRUITING

Department of Oncology and Surgical Oncology for Children and Youth Institute Mother and Child

Warsaw, Poland

RECRUITING

Department of Oncology Institute "Monument - Child Health Center"

Warsaw, Poland

RECRUITING

Fundeni Clinical Institute, Pediatric Hematology and BMT

Bucharest, Romania

RECRUITING

Oncology Institute "Prof. Dr. Al. Trestioreanu", Pediatric Oncology

Bucharest, Romania

RECRUITING

Emergency Children's Hospital " Louis Turcanu, Oncology-Haematology and BMP department

Timișoara, Romania

RECRUITING

Istanbul University Istanbul Faculty of Medicine Topkapı

Istanbul, Faith, Turkey (Türkiye)

NOT YET RECRUITING

Ankara University Faculty of Medicine Children's Hospital, Department of Children Oncology and Hematology

Ankara, Mamak, Turkey (Türkiye)

RECRUITING

Erciyes University Hospitals Kanka Children's Hematology Oncology and Bone Marrow Hospital

Kayseri, Melikgazi, Turkey (Türkiye)

RECRUITING

Gazi University Gazi Hospital Children Hematology and Oncology

Ankara, Turkey (Türkiye)

RECRUITING

Hacettepe University Hospitals Oncology Hospital 2nd Floor Children Oncology

Ankara, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Nausea; Vomiting

Interventions

Palonosetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Tulla Spinelli Head of Clinical Affairs, PharmD, PhD

CONTACT

+41919852121; tulla.spinelli@helsinn.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * Cohort 1: Single-day HEC and single-dose administration of Test Treatment (IV NEPA) or administration of Reference Treatment (IV fosaprepitant + IV ondansetron) on Day 1. Due to fosaprepitant and ondansetron not being indicated in patients younger than 6 months of age and due to fosaprepitant not being indicated in patients with body weight \<6 kg, in Cohort 1, patients aged \<6 months will exclusively receive the Test Treatment. Patients aged ≥6 months and weighing at least 6 kg will be randomly allocated to either Test Treatment or Reference Treatment. * Cohort 2: Multi-day HEC and repeated-dose administration of Test Treatment (IV NEPA), with the first administration on Day 1. All patients will receive the Test Treatment

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: April 1, 2025
• Study Start: July 7, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 31, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

PL (10); RO (3); GR (2); TU (5)