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IV NEPA (fosnetupitant/palonosetron) to prevent chemotherapy-related nausea and vomiting in children receiving highly emetogenic chemotherapy

A Multicentre, Multinational, Pharmacokinetic, Safety, and Efficacy Study With IV NEPA (Fosnetupitant/Palonosetron) for the Prevention of Chemotherapy-induced Nausea and Vomiting in Paediatric Cancer Patients Undergoing Highly Emetogenic Chemotherapy (HEC). A 2-part Study With Phase 2, Open-label, Randomised, Single-dose IV NEPA vs Fosaprepitant/Ondansetron in Single-day HEC and Repeated-dose IV NEPA in Multi-day HEC (Part I, Single Cycle) and With Phase 3, Double-blind, Randomised, Repeated-dose IV NEPA vs Fosaprepitant/Ondansetron in Multi-day HEC (Part II, Repeated Cycles)

Phase 2 Interventional Helsinn Healthcare SA · NCT06904235

This trial tests a single-dose IV combination (IV NEPA) to prevent nausea and vomiting in children and adolescents receiving highly emetogenic chemotherapy.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment95 (estimated)
Ages0 Months to 18 Years
SexAll
SponsorHelsinn Healthcare SA Industry-sponsored
Drugs / interventionschemotherapy, prednisone
Locations20 sites (Athens and 19 other locations)
Trial IDNCT06904235 on ClinicalTrials.gov

What this trial studies

Part I is an open-label Phase 2 study using an age de-escalation approach with safety checks as the drug is first tested in children. Cohort 1 will be randomized for a single-day highly emetogenic chemotherapy cycle to compare single-dose IV NEPA versus a standard-of-care regimen (fosaprepitant plus ondansetron), while Cohort 2 will assess repeated dosing of IV NEPA for multi-day highly emetogenic regimens. The medication is delivered by intravenous infusion and the study focuses on a single chemotherapy cycle for safety and initial efficacy signals. Enrollment includes children from newborns up to under 18 years, with weight thresholds and consent/assent requirements applied before dosing.

Who should consider this trial

Good fit: Children from birth (0 months) up to under 18 years with a confirmed malignancy who are scheduled to receive highly emetogenic chemotherapy and meet the study weight, life-expectancy, and consent/assent criteria are ideal candidates.

Not a fit: Patients receiving low- or moderately emetogenic chemotherapy, those with contraindications or known allergies to NK1 or 5-HT3 antagonists, or those who do not meet the weight or life-expectancy thresholds are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, IV NEPA could reduce frequency and severity of chemotherapy-induced nausea and vomiting in pediatric patients, improving comfort and adherence to cancer treatment.

How similar studies have performed: Similar fixed-dose combinations (oral NEPA) have shown good efficacy in adults, but IV NEPA has not previously been tested in pediatric patients and is novel in this population.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

The following inclusion criteria must be checked prior to study inclusion:

1. 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.
2. Male or female in- or out-patient from 0 months (newborns) to \<18 years on the date of enrolment (Day 1).
3. 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.
4. Patient with a predicted life expectancy ≥3 months according to Investigator's opinion.
5. 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.
6. 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).
7. For patients aged ≥10 years: Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Male or female fertile patient using reliable contraceptive measures. Such measures, for patient and sexual partner, include: implants, injectables, combined oral contraceptives, intrauterine devices, vasectomized/sterilized partner, use of a double barrier method, or sexual abstinence. The patient and his/her parent(s)/legal guardian must be counselled on the importance of avoiding pregnancy before and during the study.

Exclusion Criteria:

1. The patient and/or parent(s)/legal guardian are expected by the Investigator to be non compliant with the study procedures.
2. 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.
3. Known history of allergy to any component of the study treatments or other contraindications to any NK1-RAs or 5-HT3-RAs.
4. Active infection.
5. Any illness or condition that, in the opinion of the Investigator, may pose unwarranted risks in administering the investigational product to the patient.
6. Uncontrolled medical condition (e.g., uncontrolled insulin-dependent diabetes mellitus).
7. 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.
8. 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).
9. 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)
   * 5-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)
   * Anticholinergics (e.g., scopolamine, except the inhaled anticholinergics for respiratory disorders e.g., ipratropium bromide)
   * Antihistamines (e.g., diphenhydramine, cyclizine, hydroxyzine, chlorphenhyramine, dimenhydrinate, meclizine)
   * Domperidone
   * Mirtazapine
   * Olanzapine
   * Prescribed cannabinoids (e.g., tetrahydrocannabinol, nabilone)
   * Over-the-counter (OTC) antiemetics, OTC cold medications, or OTC allergy medications
   * Herbal preparations containing ephedra or ginger
10. Patient who received palonosetron within 1 week prior to administration of study treatment on Day 1.
11. Patient receiving systemic corticosteroid therapy above 0.14mg/kg or \>10 mg of prednisone daily or equivalent.

    Exception:

    Dexamethasone for the prevention of CINV is permitted in association with the study treatment (Test Treatment and Reference Treatment) as per standard of care and applicable guidelines, provided its dosage is reduced by 50% in consideration of known interactions with various NK1 RAs, including fosaprepitant and fosnetupitant.
12. Patient aged \<6 years who received any investigational drug (defined as a medication with no marketing authorization granted for any age or indication) within 90 days prior to Day 1, or patient aged ≥6 years who received any investigational drug within 30 days prior to Day 1, or patient any age who is expected to receive investigational drugs prior to study completion.
13. Intake of alcohol, food, or beverages (e.g., grapefruit, cranberry, pomegranate, and aloe vera juices; German chamomile) known to interfere with CYP3A4 or CYP2D6 metabolic enzymes within 1 week prior to Day 1 and during the overall study period.
14. Use of any drugs or substances known to be strong inhibitors of CYP3A4 or CYP2D6 enzymes within 1 week prior to Day 1 or planned to be used during the overall study period.
15. Use of any drugs or substances known to be CYP3A4 substrates with narrow therapeutic range within 1 week prior to Day 1 or planned to be used during the overall study period.
16. Use of any drugs or substances known to be strong inducers of CYP3A4 or CYP2D6 enzymes within 4 weeks prior to Day 1 or planned to be used during the overall study period.
17. Lactating female patient.
18. Enrolment in a previous study on netupitant (either administered alone or in combination with palonosetron).
19. Marked baseline prolongation of QTc interval (QTcF\>460 millisecond \[msec\]). At the discretion of the investigator, criterion may be based on automatic interpretation of results.

Where this trial is running

Athens and 19 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Nausea and Vomiting Chemotherapy-InducedNausea Post ChemotherapyPrevention of chemotherapy-induced nausea and vomitinghighly emetogenic chemotherapyHECIV NEPACINV
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.