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