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

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.