Efficacy and Safety of Palonosetron Intravenous in Prevention of Chemotherapy Induced Nausea and Vomiting in Pediatric Patients
Condition: Chemotherapy-Induced Nausea and Vomiting
MeSH terms: Nausea; Vomiting
Intervention: Palonosetron; Palonosetron; Ondansetron; Placebo to Ondansetron; Placebo to Ondansetron; Placebo to Palonosetron
Intervention description: Single dose Palonosetron IV 10 mcg/kg up to a maximum total dose of 0.75 mg; Single dose Palonosetron IV 20 mcg/kg up to a maximum total dose of 1.5 mg; Single three (every 4 hours) Ondansetron IV doses 0.15 mg/kg up to a maximum total dose of 32 mg
Intervention MeSH terms: Ondansetron; Palonosetron
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 502.0
Sex: All
Maximum age: 16 Years
Healthy volunteers: No
Keywords: Prevention of Chemotherapy-Induced Nausea and Vomiting; Palonosetron; Ondansetron; Pediatric

Summary:

      The primary objective is to evaluate the efficacy of two different doses of IV palonosetron
      in the prevention of chemotherapy induced nausea and vomiting in MEC and HEC patients through
      120 hours after start of chemotherapy in single and repeated chemotherapy cycles. The
      secondary objectives are to evaluate the safety and tolerability of IV palonosetron in
      pediatric patients and evaluate the pharmacokinetics of IV palonosetron in a subset of
      pediatric CINV patients.
    

Eligibility criteria:

        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