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Badanie z IV NEPA (Fosnetupitant/Palonosetron) w celu zapobiegania nudnościom indukowanym chemioterapią i wymiotach u pacjentów z rakiem pediatrycznym poddawanym wysoce emetogennej chemioterapii (HEC)

28 września 2026 zaktualizowane przez: Helsinn Healthcare SA

Wieloośrodkowe, międzynarodowe, farmakokinetyczne, bezpieczeństwa i skuteczności z IV NEPA (Fosnetupitant/Palonosetron) w celu zapobiegania nudnościom indukowanym chemioterapią i wymiotowaniu u pacjentów z rakiem pediatrycznym poddawanym wysoce emetogennej chemioterapii (HEC). 2-częściowe badanie z fazą 2, otwartą, randomizowaną, randomizowaną, pojedynczą dawką IV NEPA vs fosaprepitant/ondansetron w jednodniowym NEPA HEC i powtarzanej Dose IV NEPA w wielodniowym HEC (część I, pojedynczy cykl) i z fazą 3, podwójnie ślepa, losowo-losowa, losowo, powtarzane Dose IV NEPA VS IV NEPA VS Cykle)

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

Przegląd badań

Status

Rekrutacyjny

Warunki

Interwencja / Leczenie

Szczegółowy opis

Part I of the study is a Phase 2, open-label, randomised (for Cohort 1 only), single chemotherapy cycle study which will compare single-dose of IV NEPA to another treatment (fosaprepitant/ondansetron) considered as a standard of care, in patients receiving single-day chemotherapy that has a high possibility to generate a vomiting episode (HEC) (Cohort 1) and assess repeated dose of IV NEPA in patients receiving multi day HEC chemotherapy (Cohort 2).

Because this will be the first study testing the IV NEPA in children, Part I will enroll patients from older to younger age groups with safety checks before moving to the next group.

Typ studiów

Interwencyjne

Zapisy (Szacowany)

95

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Lokalizacje studiów

  • Grecja
      • Athens, Grecja
        • Rekrutacyjny
        • Aghia Sophia Children's Hospital, Pediatric Hematology/ Oncology Unit (POHemU)
      • Thessaloniki, Grecja
        • Wycofane
        • "AHEPA" University General Hospital of Thessaloniki, 2nd Department of Pediatrics
  • Polska
      • Bialystok, Polska
        • Wycofane
        • Department of Pediatrics, Oncology and Hematology University Children's Clinical Hospital them. Ludwik Zamenhof in Bialystok
      • Bydgoszcz, Polska, 85-667
        • Rekrutacyjny
        • Department of Paediatrics, Haematology, Oncology and Rheumatology Voivodship Children's Hospital them. J. Brudziński
      • Lodz, Polska
        • Rekrutacyjny
        • Clinic of Pediatrics, Oncology and Hematology University Pediatric Center them M. Konopnicka SP ZOZ Central Clinical Hospital Medical University of Lodz
      • Lublin, Polska, 20-093
        • Jeszcze nie rekrutacja
        • University Children'S Hospital in Lublin, Department of Pediatric Hematology, Oncology, and Transplantology
      • Olsztyn, Polska
        • Wycofane
        • Clinical Department of Paediatric Oncology and Haematology VOIVODSHIP SPECIALIST CHILDREN'S HOSPITAL them. prof. dr. Stanisław Popowski in Olsztyn
      • Poznan, Polska
        • Rekrutacyjny
        • Department of Pediatric Oncology, Hematology and Transplantation Clinical Hospital them. Karol Jonscher Medical University them. Karol Marcinkowski in Poznań
      • Szczecin, Polska
        • Wycofane
        • Department of Paediatrics and Paediatric Haemato-Oncology University Clinical Hospital No. 1 them. prof. Tadeusz Sokołowski Pomeranian Medical University
      • Szczecin, Polska
        • Wycofane
        • Department of Paediatrics, Oncology and Paediatric Immunology, University Clinical Hospital No. 1 them. prof. Tadeusz Sokołowski Pomeranian Medical University in Szczecin
      • Warsaw, Polska
        • Rekrutacyjny
        • Department of Oncology and Surgical Oncology for Children and Youth Institute Mother and Child
      • Warsaw, Polska
        • Rekrutacyjny
        • Department of Oncology Institute "Monument - Child Health Center"
  • Rumunia
      • Bucharest, Rumunia
        • Rekrutacyjny
        • Fundeni Clinical Institute, Pediatric Hematology and BMT
      • Bucharest, Rumunia
        • Rekrutacyjny
        • Oncology Institute "Prof. Dr. Al. Trestioreanu", Pediatric Oncology
      • Timișoara, Rumunia
        • Rekrutacyjny
        • Emergency Children's Hospital " Louis Turcanu, Oncology-Haematology and BMP department
  • Turcja (Türkiye)
      • Ankara, Turcja (Türkiye)
        • Rekrutacyjny
        • Gazi University Gazi Hospital Children Hematology and Oncology
      • Ankara, Turcja (Türkiye)
        • Rekrutacyjny
        • Hacettepe University Hospitals Oncology Hospital 2nd Floor Children Oncology
    • Faith
      • Istanbul, Faith, Turcja (Türkiye)
        • Jeszcze nie rekrutacja
        • Istanbul University Istanbul Faculty of Medicine Topkapı
    • Mamak
      • Ankara, Mamak, Turcja (Türkiye)
        • Rekrutacyjny
        • Ankara University Faculty of Medicine Children's Hospital, Department of Children Oncology and Hematology
    • Melikgazi
      • Kayseri, Melikgazi, Turcja (Türkiye)
        • Rekrutacyjny
        • Erciyes University Hospitals Kanka Children's Hematology Oncology and Bone Marrow Hospital

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

1 sekunda do 18 lat (Dziecko, Dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Zapobieganie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: IV NEPA

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.
Lek: IV NEPA (fosnetupitant/palonosetron)

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).
Aktywny komparator: Reference Treatment

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.
Lek: Reference Treatment: IV ondansetron infusion

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)
Lek: Reference Treatment: IV fosaprepitant infusion

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)

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
COHORT 1 Neptupitant exposure parameter
Ramy czasowe: From time zero ( start of IV NEPA infusion) to maximum 168 hours

Maximum concentration (Cmax)
From time zero ( start of IV NEPA infusion) to maximum 168 hours
COHORT 1 Neptupitant exposure
Ramy czasowe: From time zero ( start of IV NEPA infusion) to maximum 168 hours

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)
Ramy czasowe: Up to 31 days

monitoring of AEs following repeated IV NEPA administration
Up to 31 days

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
COHORT 1: To assess the PK profile of netupitant.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

Cmax of netupitant
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1: To assess the PK profile of fosnetupitant.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

Cmax of fosnetupitant
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1: To assess the PK profile palonosetron.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

Cmax of palonosetron
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1: To assess the PK profile of netupitant
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 48 hours

AUC0-48 of netupitant
From Time zero ( start of IV NEPA infusion) until 48 hours
COHORT 1: To assess the PK profile of fosnetupitant.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 48 hours

AUC0-48 of fosnetupitant
From Time zero ( start of IV NEPA infusion) until 48 hours
COHORT 1: To assess the PK profile palonosetron.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 48 hours

AUC0-48 of palonosetron
From Time zero ( start of IV NEPA infusion) until 48 hours
COHORT 1: To assess the PK profile of netupitant
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

t1/2 of netupitant
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1: To assess the PK profile of palonosetron.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

t1/2 of palonosetron
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1 and 2: To assess the population PK profile of fosnetupitant.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

Clearance (CL) of fosnetupitant
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1 and 2: To assess the population PK profile of palonosetron.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

CL of palonosetron
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1 and 2: To assess the population PK profile of netupitant.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

CL/F of netupitant
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1 and 2: To assess the population PK profile of fosnetupitant
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

Volume of compartments (V) for fosnetupitant
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1 and 2: To assess the population PK profile of palonosetron.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

V for palonosetron
From Time zero ( start of IV NEPA infusion) until 168 hours
COHORT 1 and 2: To assess the population PK profile of netupitant.
Ramy czasowe: From Time zero ( start of IV NEPA infusion) until 168 hours

V/F for netupitant
From Time zero ( start of IV NEPA infusion) until 168 hours

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Helsinn Healthcare SA

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

7 lipca 2025

Zakończenie podstawowe (Szacowany)

1 października 2027

Ukończenie studiów (Szacowany)

1 grudnia 2027

Daty rejestracji na studia

Pierwszy przesłany

16 grudnia 2024

Pierwszy przesłany, który spełnia kryteria kontroli jakości

31 marca 2025

Pierwszy wysłany (Rzeczywisty)

1 kwietnia 2025

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

29 września 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

28 września 2026

Ostatnia weryfikacja

1 września 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • NEPA-22-01
  • 2024-514321-39 (Numer EudraCT)

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

Opis planu IPD

Only global trial data will be shared, not a single patient

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Tak

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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