Study to evaluate the efficacy and safety of two different doses of palonosetron compared to ondansetron in the prevention of CINV in pediatric patients undergoing single and repeated cycles of MEC or HEC MedDRA version: 13.1 Level: LLT Classification code 10049091 Term: Chemotherapy antiemetic prophylaxis System Organ Class: 10042613 - Surgical and medical procedures MedDRA version: 13.1 Level: LLT Classification code 10036899 Term: Prophylaxis against chemotherapy induced vomiting System Org
Conditions
Sponsors
Helsinn Healthcare SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. 2. Male or female in- or out-patients from neonates (full term) to 2.5 ULN or ALT > 2.5 ULN or total bilirubin > 1.5 ULN): in the Investigator’s opinion the impairment should not jeopardize patient’s safety during the study. 9. For patients with known renal impairment (defined as creatinine >1.5 ULN): in the Investigator’s opinion the impairment should not jeopardize patient’s safety during the study. 10. 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. 11. 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. 12. Fertile patients (male or female) must use reliable contraceptive measures (such measures, for patients and sexual partners, include: implants, injectables, combined oral contraceptives, intrauterine devices, vasectomized/sterilized partner, use of a double-barrier method or sexual abstinence). 13. 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). The patient and her parent(s) must be counseled on the importance of not becoming pregnant before or during the study. Are the trial subjects under 18? yes Number of subjects for this age range: 492 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. The patient and/or parents/caregivers are expected by the Investigator to be non-compliant with the study procedures. 2. Lactating or pregnant female patient. 3. 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). 4. 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. 5. Known history of allergy to any component or other contraindications to any 5-HT3 receptor antagonists. 6. Active infection. 7. Uncontrolled medical condition (e.g., uncontrolled insulin-dependent diabetes mellitus). 8. 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. 9. 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. 10. Patient who experienced any vomiting, retching, or nausea within 24 hours prior to the administration of the study drug. 11. Patient who received any drug with potential anti-emetic effect within 24 hours prior to administration of study treatment, including but not limited to (see also Appendix F): • 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; Trimetobenzamide HCl; Meclizine hydrochloride; Pseudoephedrine HCl; • Over the Counter (OTC) antiemetics, OTC cold or OTC allergy medications; • Herbal preparations containing ephedra or ginger. 12. 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. 13. Patient who participated in any previous trial with palonosetron.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: •To evaluate the safety and tolerability of IV palonosetron in pediatric patients. •To evaluate the pharmacokinetics of IV palonosetron in a subset of pediatric CINV patients. ;Primary end point(s): The primary efficacy endpoint is the proportion of patients showing Complete Response (CR; defined as no vomiting, no retching, and no use of antiemetic rescue medication) from 0 to 24 hours after T0 (first chemotherapy dose).;Timepoint(s) of evaluation of this end point: from 0-24 hours (acute phase) after start of chemotherapy (T0) during first cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Complete response in delayed phase after T0 -Proportion of patiens showing CR during overall period Other secondary efficacy endpoints to be determined for each period (Acute, Delayed, and Overall) during first cycle are: •Proportion of patients without vomiting •Proportion of patients without emetic episodes •Proportion of patients without antiemetic rescue medication •Proportion of patients without nausea (patients aged = 6 years) •Time to first vomiting •Time to first emetic episode •Time to first administration of rescue medication •Time to treatment failure (time to first emetic episode or time to first administration of rescue medication, whichever occurs first). For the subsequent cycles the following secondary endpoints are defined for each period (Acute, Delayed, and Overall): •Proportion of patients showing CR •Proportion of patients without vomiting •Proportion of patients without emetic episodes •Proportion of patients without antiemetic rescue medication •Proportion of patients without nausea (patients aged = 6 years);Timepoint(s) of evaluation of this end point: >24 to 120 hours (delayed phase) during the first cycle 0 to 120 hours (overall period) during the first cycle | — |
Countries
Argentina, Austria, Bulgaria, Chile, Czech Republic, Estonia, France, Germany, Hungary, Peru, Poland, Romania, Russian Federation, Serbia, Ukraine, United Kingdom
Contacts
Public ContactTulla Spinelli
Helsinn Healthcare SA
Outcome results
None listed