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

For neonates (<28 days, full term) an open-label sub-study will be conducted to assess
exposure and tolerability in this age group with escalating doses of palonosetron, starting
with 3 mcg/kg to the first three or more neonates included in the study. If this dose is
shown to be safe and well tolerated then the following three neonates will be treated with a
dose of 10 mcg/kg. If also this dose is safe and well tolerated, then the following three
neonates will be treated with a dose of 20 mcg/kg. If this last dose is also shown to be
safe and well tolerated, then all the following neonates will be randomized to the main
study.

Inclusion Criteria:

- Written informed consent signed 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

- Male or female in- or out-patients from neonates (full term) to <17 years at the time
of 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 emetogenic
chemotherapeutic 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 the
impairment should not jeopardize patient's safety during the study

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

- For patients 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

- For patients with known clinically relevant abnormal laboratory values: in the
Investigator's opinion the abnormality should not jeopardize the patient's safety
during 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 the
screening 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, radiotherapy
of 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 upper
abdomen, lower thorax region, or cranium/craniospinal regions up to 24 hours after
study drug administration

- Known history of allergy to any component or other contraindications to any 5-HT3
receptor antagonists

- Active infection

- Uncontrolled medical condition

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

- 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) or patients with hydrocephalus

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

- Patient who received any drug with potential anti-emetic effect within 24 hours prior
to 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 for
respiratory disorders and topical steroids for skin disease with doses of ≤ 10 mg of
prednisone daily or its equivalent); Corticosteroids foreseen in the chemotherapy
regimen or to reduce intracranial pressure are allowed. According to the
guidelines1,2, patients will receive also dexamethasone as a co-medication in
accordance with standard clinical practice and if deemed appropriate by the
Investigator.

- 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 medication
with 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 investigational
drug within 30 days prior to Day 1 or is expected to receive investigational drugs
prior to study completion

- Patient who participated in any previous trial with palonosetron