PK/PD Study of Netupitant and Palonosetron in Pediatric Patients for Prevention of Chemotherapy-induced Nausea and Vomiting



Status:Recruiting
Healthy:No
Age Range:Any - 17
Updated:10/19/2018
Start Date:August 31, 2017
End Date:January 2019
Contact:Anastasia Eremeeva, MD
Email:Anastasia.Eremeeva@psi-cro.com
Phone:+7 812 320 38 55

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A Multicenter Multinational Randomized Double Blind PK/PD Dose-finding Study of Oral Netupitant Given With Oral Palonosetron in Pediatric Cancer Patients for Prevention of Nausea and Vomiting Associated With Emetogenic Chemotherapy

This study is Phase 2 pharmacokinetic (PK) and pharmacodynamic (PD) dose-finding study of
oral netupitant administered concomitantly with oral palonosetron in pediatric cancer
patients for the prevention of nausea and vomiting associated with emetogenic chemotherapy.
Two different netupitant dosages will be tested in patients aged from 3 months to < 18 years:
1.33 mg/kg up to a maximum of 100 mg, and 4 mg/kg up to a maximum of 300 mg. All netupitant
doses in all age classes will be concomitantly administered with palonosetron 20 μg/kg (up to
a maximum dose of 1.5 mg) which is the IV palonosetron dose approved by USA FDA for the
pediatric population. The primary objective is to investigate the PK/PD relationship between
netupitant exposure (AUC, Cmax) and antiemetic efficacy (CR in delayed phase) after a single
oral netupitant administration, concomitantly with oral palonosetron in pediatric cancer
patients receiving Moderately Emetogenic Chemotherapy (MEC) or Highly Emetogenic Chemotherapy
(HEC) cycles. Efficacy parameter to be used in the correlation is the proportion of patients
with Complete Response (CR i.e., no emetic episodes and no rescue medication) during (>
24-120 h after the start of chemotherapy on Day 1).

The secondary objectives are to assess the safety and tolerability after single oral
administration of netupitant given concomitantly with a single oral administration of
palonosetron; to evaluate the pharmacokinetic (AUC, Cmax, tmax and t1/2) of oral palonosetron
at the fixed dose of 20 μg/kg in pediatric patients with the concomitant administration of
netupitant. A total of 92 pediatric cancer patients receiving either HEC or MEC will be
enrolled in the study.


Inclusion Criteria:

1. Signed written informed consent by parent(s)/legal guardians of the pediatric patient
in compliance with the local laws and regulations. In addition signed children's
assent form according to local requirements.

2. Male or female in- or out-patient from birth to < 18 years at the time of
randomization.

3. Patient weight at least 3.3 kg.

4. Naïve or non-naïve patient with histologically, and/or cytologically (or imaging in
the case of brain tumors) confirmed malignant disease.

5. Scheduled and eligible to receive at least one moderately or highly emetogenic
chemotherapeutic agent on Day 1 only or for multiple days.

6. For patient aged ≥ 10 years: Eastern Cooperative Oncology Group Performance Status
(ECOG PS) ≤ 2.

7. For patient aged 2 years with known mild to moderate hepatic impairment: in the
Investigator's opinion the impairment does not jeopardize patient's safety during the
study.

8. For patient aged 2 years with known mild to moderate renal impairment: in the
Investigator's opinion the impairment should not jeopardize patient's safety during
the study.

9. For patient with known history or predisposition to cardiac abnormalities: in the
Investigator's opinion the history/predisposition should not jeopardize patient's
safety during the study.

10. If the patient is female, she shall: a) not have attained menarche yet or b) have
attained menarche and have a negative pregnancy test at the screening visit and at Day
1.

11. 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
guardians must be counseled on the importance of avoiding pregnancy before or during
the study.

Exclusion Criteria:

1. The patient and/or parents/caregivers 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, 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
administration on Day 1.

3. Known history of allergy to any component or other contraindications to any
Neurokinin-1 (NK1) or 5-hydroxytryptamine 3 (5-HT3) receptor antagonists.

4. Active infection.

5. Uncontrolled medical condition (e.g., uncontrolled insulin dependent diabetes
mellitus).

6. Patient suffering from ongoing vomiting from any organic etiology (including patients
with history of gastric outlet obstruction or intestinal obstruction due to adhesions
or volvulus, patients with a symptomatic central nervous system(CNS) tumor causing
nausea and/or vomiting) or patient with hydrocephalus.

7. Patient who experienced any vomiting, retching, or nausea within 24 h prior to the
administration of the study drug

8. Patient who received any drug with potential anti-emetic effect within 24 h prior to
the start of reference chemotherapy, including but not limited to:

NK1- receptor antagonists (e.g., aprepitant or any other new drug of this class);
5-HT3 receptor antagonists (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 drug administration
or expected to be received within 120 h following initiation of chemotherapy, except
for single doses of midazolam, temazepam or triazolam; Butyrophenones (e.g.,
droperidol, haloperidol); Anticholinergics (e.g., scopolamine, with the exception of
inhaled anticholinergics for respiratory disorders e.g., ipratropium bromide);
Antihistamines (e.g., diphenhydramine, cyclizine, hydroxyzine, chlorpheniramine,
dimenhydrinate, meclizine); Domperidone; Mirtazapine; Olanzapine; Prescribed
cannabinoids (e.g., tetrahydrocannabinol, nabilone); Over the Counter (OTC)
antiemetics, OTC cold or OTC allergy medications; Herbal preparations containing
ephedra or ginger.

9. Patient who received palonosetron within 1 week prior to administration of study drug.

10. Patient who has been started on systemic corticosteroid therapy within 72 h prior to
study drug administration or is planned to receive a corticosteroid as part of the
chemotherapy regimen

11. Patient aged < 6 years who received any investigational drug (defined as a medication
with no marketing authorization granted for any age class and any 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 is expected to receive investigational drugs prior to
study completion.

12. Intake of alcohol, food or beverages (e.g., grapefruit, cranberry, pomegranate and
aloe vera juices, German chamomile) known to interfere with either CYP3A4 or CYP2D6
metabolic enzymes within 1 week prior to Day 1 and during the overall study period.

13. Use of any drugs or substances known to be strong or moderate inhibitors of CYP3A4 and
CYP2D6 enzymes within 1 week prior to Day 1 or planned to be used during the overall
study period.

14. 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.

15. Use of any drugs or substances known to be inducers of CYP3A4 enzymes within 4 weeks
prior to Day 1 or planned to be used during the overall study period.

16. Lactating female patient.

17. Patient with clinically relevant abnormal laboratory values that in the Investigator's
opinion jeopardize the patient's safety during the study.

18. Patient aged < 2 years with known hepatic impairment (any grade), or patient aged 2
years with known severe hepatic impairment.

19. Patient aged < 2 years with known renal impairment (any grade), or patient aged 2
years with known severe renal impairment.

20. Enrolment in a previous study with netupitant (either alone or in combination with
palonosetron).
We found this trial at
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Wilmington, Delaware 19803
Phone: 302-651-5500
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807 Childrens Way
Jacksonville, Florida 32207
(904) 697-3600
Phone: 904-697-3896
Nemours Children's Clinic At Nemours Children’s Clinic, Jacksonville, we've treated every child as we would...
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171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Phone: 843-792-2957
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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42А ulitsa Blyukhera
Chelyabinsk, 454087
Phone: +7 (351) 261 1371
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Orlando, Florida 32827
Phone: 407-650-7652
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100 Campus Drive
Scarborough, Maine 04074
Phone: 207-885-7565
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