Efficacy and Safety of Palonosetron Intravenous in Prevention of Chemotherapy Induced Nausea and Vomiting in Pediatric Patients

Inclusion Criteria:

• Written informed consent signed by parent(s)/legal guardians of the pediatric patientin compliance with the local laws and regulations. In addition signed children'sassent form according to local requirements

• Male or female in- or out-patients from neonates (full term) to <17 years at the timeof randomization

• Patient weight at least 3.2 kg

• Histologically, and/or cytologically (or imaging in the case of brain tumors)confirmed malignant disease

• Naïve or non-naïve to chemotherapy

• Scheduled and eligible to receive at least one of the moderately or highly emetogenicchemotherapeutic agents on Study Day 1

• For patients aged ≥ 10 years to <17 years: ECOG PS ≤ 2

• For patients with known hepatic impairment: in the Investigator's opinion theimpairment should not jeopardize patient's safety during the study

• For patients with known renal impairment: in the Investigator's opinion the impairmentshould not jeopardize patient's safety during the study

• For patients with known history or predisposition to cardiac abnormalities: in theInvestigator's opinion the history/predisposition should not jeopardize patient'ssafety during the study

• For patients with known clinically relevant abnormal laboratory values: in theInvestigator's opinion the abnormality should not jeopardize the patient's safetyduring the study

• Fertile patients (male or female) must use reliable contraceptive measures

• Female patients who have attained menarche must have a negative pregnancy test at thescreening visit (Visit 1) and at study treatment visit (Visit 2)

Exclusion Criteria:

• Lactating or pregnant female patient

• Patient has received total body irradiation, upper abdomen radiotherapy, radiotherapyof the cranium, craniospinal regions or the pelvis within 1 week prior to study entry (screening)

• Scheduled to receive concomitant total body irradiation, radiotherapy of the upperabdomen, lower thorax region, or cranium/craniospinal regions up to 24 hours afterstudy drug administration

• Known history of allergy to any component or other contraindications to any 5-HT3receptor antagonists

• Active infection

• Uncontrolled medical condition

• Marked baseline prolongation of QTc interval [QTcB or QTcF > 460 msec] in any of theECG assessments at screening. For this purpose, assessment will rely on the automaticinterpretation by the ECG machine

• Patient suffering from ongoing vomiting from any organic etiology (including patientswith history of gastric outlet obstruction or intestinal obstruction due to adhesionsor volvulus) or patients with hydrocephalus

• Patient who experienced any vomiting, retching, or nausea within 24 hours prior to theadministration of the study drug

• Patient who received any drug with potential anti-emetic effect within 24 hours priorto administration of study treatment, including but not limited to:

• NK1- receptor antagonists (e.g. aprepitant)

• 5-HT3 antagonists (e.g., ondansetron, granisetron, dolasetron);

• Phenothiazines (e.g., perphenazine, prochlorperazine, promethazine, fluphenazine,chlorpromazine, thiethylperazine);

• Butyrophenones (e.g., droperidol, haloperidol);

• Benzamides (e.g., metoclopramide, alizapride);

• Corticosteroids (e.g., prednisone, methylprednisolone; except inhaled steroids forrespiratory disorders and topical steroids for skin disease with doses of ≤ 10 mg ofprednisone daily or its equivalent); Corticosteroids foreseen in the chemotherapyregimen or to reduce intracranial pressure are allowed. According to theguidelines1,2, patients will receive also dexamethasone as a co-medication inaccordance with standard clinical practice and if deemed appropriate by theInvestigator.

• Dimenhydrinate; Hydroxyzine; Domperidone; Lorazepam; Cyclizine; Cannabinoids;Scopolamine; Trimethobenzamide HCl; Meclizine hydrochloride; Pseudoephedrine HCl;

• Over the Counter (OTC) antiemetics, OTC cold or OTC allergy medications;

• Herbal preparations containing ephedra or ginger.

• Patient aged ≤ 6 years who received any investigational drug (defined as a medicationwith no marketing authorization granted for any age group and any indication) within 90 days prior to Day 1, or patient aged > 6 years who received any investigationaldrug within 30 days prior to Day 1 or is expected to receive investigational drugsprior to study completion

• Patient who participated in any previous trial with palonosetron