Clinical trial NCT01442376: Efficacy and Safety of Palonosetron Intravenous in Prevention of Chemotherapy Induced Nausea and Vomiting in Pediatric Patients
Official title: A Multicenter, Randomized, Double-blind, Parallel Group 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-Induced Nausea and Vomiting
Keywords: Prevention of Chemotherapy-Induced Nausea and Vomiting
Palonosetron
Ondansetron
Pediatric
Lead sponsor: Helsinn Healthcare SA
Sponsor class: INDUSTRY
First posted: 2011-09-28
Enrollment: 502
Sex: ALL
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Proportion of Patients With Complete Response 0 to 24 Hours (Acute Phase) in Cycle 1
timeFrame: 0 to 24 hours after T0
Secondary outcomes:
measure: Proportion of Patients With Complete Response >24 to 120 Hours (Delayed Phase) in Cycle 1
timeFrame: from >24 to 120 hours (delayed phase) after T0
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Wilmington
country: United States
facility: A. I. duPont Hospital for Children
state: Delaware
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic-Orlando
state: Florida
city: Pensacola
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Savannah
country: United States
facility: Backus Children's Hospital at University Pediatrics
state: Georgia
city: Lexington
country: United States
facility: University of Kentucky - Chandler Medical Center
state: Kentucky
city: Syracuse
country: United States
facility: Upstate Medical University
state: New York
city: Valhalla
country: United States
facility: Department of Pediatrics
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Buenos Aires
country: Argentina
facility: CEMIC
city: Cordoba
country: Argentina
facility: Hospital Privado Centro Medico de Cordoba
city: El Palomar
country: Argentina
facility: Hospital Nacional "Prof. Dr. Alejandro Posadas"
city: Wien
country: Austria
facility: Children's Cancer Research Institute
city: Wien
country: Austria
facility: Medical University of Vienna
city: Plovdiv
country: Bulgaria
facility: Pediatrics and Genetic Medicine Clinic
city: Sofia
country: Bulgaria
facility: Specialised Hospital for Active Treatment of Oncohematological Diseases in Children
city: Varna
country: Bulgaria
facility: Specialised Pediatric Clinic of Clinical Hematology and Oncology Mutiprofile Hospital for Active Treatment "Sveta Marina"
city: Santiago
country: Chile
facility: Hospital Dr Luis Calvo Mackenna
city: Santiago
country: Chile
facility: Clinica Santa Maria SA
city: Santiago
country: Chile
facility: Hospital Clinico UC
city: Santiago
country: Chile
facility: Clinica Davila
city: Brno
country: Czech Republic
facility: University Hospital Brno, Children's Medical Centre, Clinic of Pediatric Oncology
city: Ostrava
country: Czech Republic
facility: University Hospital in Ostrava, Clinic of Pediatric
city: Plzen-Lochotin
country: Czech Republic
facility: University Hospital in Pilsen
city: Praha 5
country: Czech Republic
facility: University Hospital Motol, Department of Paediatric Heamatology and Oncology
city: Tallinn
country: Estonia
facility: Tallin Children's Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital, Hematology - Oncology Clinic
city: Lille Cedex
country: France
facility: CHRU de Lille - Hopital d'Hematologie Pediatrique
city: Montpellier
country: France
facility: Hopital Arnaud de Villenueve
city: Tours Cedex 09
country: France
facility: CHRU de Tours - Centre de Pediatrie Gatien de Clocheville
city: Cologne
country: Germany
facility: University Hospital of Cologne
city: Freiburg
country: Germany
facility: University Medical Center Freiburg
city: Budapest
country: Hungary
facility: Semmelweis University, 2nd Department of Pediatrics
city: Szeged
country: Hungary
facility: University of Szeged, Szent-Gyorgyl Albert Clinical Center, Department of Pediatrics
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplásicas
city: Lima
country: Peru
facility: Oncosalud SAC RCI 300
city: San Isidro Lima
country: Peru
facility: Clinica Anglo Americana - Centro de Investigacion Oncologica CAA
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki - Department of Pediatrics, Hematology and Oncology
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lodz
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital
city: Lublin
country: Poland
facility: Dzieciecy Szpital Kliniczny
city: Warsaw
country: Poland
facility: Institut Pomnik - The Children Memorial Health Institute, Department of Oncology
city: Wroclaw
country: Poland
facility: Samodzielny Publiczny Szpital
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute, Pediatrics Clinic
city: Bucharest
country: Romania
facility: "Prof. Dr. Alexandru Trestioreanu" Institute of Oncology, Pediatric Oncology Department
city: Cluj
country: Romania
facility: "Prof. Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca Pediatric Department
city: Iasi
country: Romania
facility: Sf. Maria - Chidren's Emergency Clinical Hospital
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Pediatric Regional Clinical Hospital, Oncohematology Department
city: Ekaterinburg
country: Russian Federation
facility: Regional Pediatric Clinical Hospital #1
city: Krasnodar
country: Russian Federation
facility: Pediatric Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center
city: Moscow
country: Russian Federation
facility: Moscow State Institution: Morozovskaya Pediatric City Clinical Hospital
city: Omsk
country: Russian Federation
facility: Omsk Regional Clinical Oncology Center
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Medical University
city: St. Petersburg
country: Russian Federation
facility: State Clinical Hospital
city: Belgrade
country: Serbia
facility: Department for hematology and oncology
city: Nis
country: Serbia
facility: Clinical Center Nis, Clinic for pediatrics internal diseases, Department for hematology and oncology
city: Donetsk
country: Ukraine
facility: State Institution: V. K. Husak Institute of Urgent and Reconstructive Surgery
city: Donetsk
country: Ukraine
facility: Public Treatment and Prophylaxis Institution: Regional Children's Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Public Healthcare Institution: Regional Children's Clinical Hospital #1
city: Kyiv
country: Ukraine
facility: National Institute of Cancer
Study officials:
References:
citation: Kovacs G, Wachtel AE, Basharova EV, Spinelli T, Nicolas P, Kabickova E. Palonosetron versus ondansetron for prevention of chemotherapy-induced nausea and vomiting in paediatric patients with cancer receiving moderately or highly emetogenic chemotherapy: a randomised, phase 3, double-blind, double-dummy, non-inferiority study. Lancet Oncol. 2016 Mar;17(3):332-344. doi: 10.1016/S1470-2045(15)00520-3. Epub 2016 Jan 19.