Efficacy and Safety of Palonosetron Intravenous in Prevention of Chemotherapy Induced Nausea and Vomiting in Pediatric Patients
- Conditions
- Chemotherapy-Induced Nausea and Vomiting
- Interventions
- Registration Number
- NCT01442376
- Lead Sponsor
- Helsinn Healthcare SA
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 502
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Palonosetron 10 mcg/kg Placebo to Ondansetron Palonosetron and placebo to Ondansetron Intervention: Drug: Palonosetron Palonosetron 20 mcg/kg Placebo to Ondansetron Palonosetron and placebo to Ondansetron Intervention: Drug: Palonosetron Ondansetron Placebo to Palonosetron Ondansetron and placebo to Palonosetron Drug: Comparator: Ondansetron Palonosetron 10 mcg/kg Palonosetron Palonosetron and placebo to Ondansetron Intervention: Drug: Palonosetron Palonosetron 20 mcg/kg Palonosetron Palonosetron and placebo to Ondansetron Intervention: Drug: Palonosetron Ondansetron Ondansetron Ondansetron and placebo to Palonosetron Drug: Comparator: Ondansetron
- Primary Outcome Measures
Name Time Method Proportion of Patients With Complete Response 0 to 24 Hours (Acute Phase) in Cycle 1 0 to 24 hours after T0 Complete Response (CR) was defined as no vomiting, no retching, and no use of antiemetic rescue medication from 0 to 24 hours (acute phase) after T0 (start of administration of the most emetogenic chemotherapy) during first cycle. Time 0 (T0) is defined as the time when the patient starts the first cycle of chemotherapy.
- Secondary Outcome Measures
Name Time Method Proportion of Patients With Complete Response >24 to 120 Hours (Delayed Phase) in Cycle 1 from >24 to 120 hours (delayed phase) after T0 Complete Response (CR) was defined as no vomiting, no retching, and no use of antiemetic rescue medication from \>24 to 120 hours (delayed phase) after T0 (start of administration of the most emetogenic chemotherapy) during first cycle.
Trial Locations
- Locations (66)
A. I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Nemours Children's Clinic
🇺🇸Pensacola, Florida, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Clinica Davila
🇨🇱Santiago, Chile
Specialised Hospital for Active Treatment of Oncohematological Diseases in Children
🇧🇬Sofia, Bulgaria
Hospital Dr Luis Calvo Mackenna
🇨🇱Santiago, Chile
Clinica Santa Maria SA
🇨🇱Santiago, Chile
Hospital Clinico UC
🇨🇱Santiago, Chile
University Hospital in Ostrava, Clinic of Pediatric
🇨🇿Ostrava, Czech Republic
Instituto Nacional de Enfermedades Neoplásicas
🇵🇪Lima, Peru
University Hospital in Pilsen
🇨🇿Plzen-Lochotin, Czech Republic
University Hospital Motol, Department of Paediatric Heamatology and Oncology
🇨🇿Praha 5, Czech Republic
Tallin Children's Hospital
🇪🇪Tallinn, Estonia
Tartu University Hospital, Hematology - Oncology Clinic
🇪🇪Tartu, Estonia
Clinica Anglo Americana - Centro de Investigacion Oncologica CAA
🇵🇪San Isidro Lima, Peru
Szpital Uniwersytecki - Department of Pediatrics, Hematology and Oncology
🇵🇱Bydgoszcz, Poland
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital
🇵🇱Lodz, Poland
Fundeni Clinical Institute, Pediatrics Clinic
🇷🇴Bucharest, Romania
St. Petersburg State Medical University
🇷🇺St. Petersburg, Russian Federation
Pediatric Regional Clinical Hospital
🇷🇺Krasnodar, Russian Federation
Upstate Medical University
🇺🇸Syracuse, New York, United States
Department of Pediatrics
🇺🇸Valhalla, New York, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Nemours Children's Clinic-Orlando
🇺🇸Orlando, Florida, United States
University of Kentucky - Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Backus Children's Hospital at University Pediatrics
🇺🇸Savannah, Georgia, United States
Hospital Italiano de Buenos Aires
🇦🇷Buenos Aires, Argentina
Hospital Privado Centro Medico de Cordoba
🇦🇷Cordoba, Argentina
Institut Pomnik - The Children Memorial Health Institute, Department of Oncology
🇵🇱Warsaw, Poland
Samodzielny Publiczny Szpital
🇵🇱Wroclaw, Poland
Russian Oncology Research Center
🇷🇺Moscow, Russian Federation
Omsk Regional Clinical Oncology Center
🇷🇺Omsk, Russian Federation
State Clinical Hospital
🇷🇺St. Petersburg, Russian Federation
Department for hematology and oncology
🇷🇸Belgrade, Serbia
Clinical Center Nis, Clinic for pediatrics internal diseases, Department for hematology and oncology
🇷🇸Nis, Serbia
Public Healthcare Institution: Regional Children's Clinical Hospital #1
🇺🇦Kharkiv, Ukraine
State Institution: V. K. Husak Institute of Urgent and Reconstructive Surgery
🇺🇦Donetsk, Ukraine
National Institute of Cancer
🇺🇦Kyiv, Ukraine
Public Treatment and Prophylaxis Institution: Regional Children's Clinical Hospital
🇺🇦Donetsk, Ukraine
The Children's Hospital
🇺🇸Aurora, Colorado, United States
Hospital Nacional "Prof. Dr. Alejandro Posadas"
🇦🇷El Palomar, Argentina
CEMIC
🇦🇷Buenos Aires, Argentina
University Hospital Brno, Children's Medical Centre, Clinic of Pediatric Oncology
🇨🇿Brno, Czech Republic
University Medical Center Freiburg
🇩🇪Freiburg, Germany
Pediatrics and Genetic Medicine Clinic
🇧🇬Plovdiv, Bulgaria
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Specialised Pediatric Clinic of Clinical Hematology and Oncology Mutiprofile Hospital for Active Treatment "Sveta Marina"
🇧🇬Varna, Bulgaria
Children's Cancer Research Institute
🇦🇹Wien, Austria
Medical University of Vienna
🇦🇹Wien, Austria
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
University of Szeged, Szent-Gyorgyl Albert Clinical Center, Department of Pediatrics
🇭🇺Szeged, Hungary
CHRU de Tours - Centre de Pediatrie Gatien de Clocheville
🇫🇷Tours Cedex 09, France
Semmelweis University, 2nd Department of Pediatrics
🇭🇺Budapest, Hungary
University Hospital of Cologne
🇩🇪Cologne, Germany
CHRU de Lille - Hopital d'Hematologie Pediatrique
🇫🇷Lille Cedex, France
Hopital Arnaud de Villenueve
🇫🇷Montpellier, France
Oncosalud SAC RCI 300
🇵🇪Lima, Peru
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Dzieciecy Szpital Kliniczny
🇵🇱Lublin, Poland
Chelyabinsk Pediatric Regional Clinical Hospital, Oncohematology Department
🇷🇺Chelyabinsk, Russian Federation
"Prof. Dr. Alexandru Trestioreanu" Institute of Oncology, Pediatric Oncology Department
🇷🇴Bucharest, Romania
"Prof. Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca Pediatric Department
🇷🇴Cluj, Romania
Sf. Maria - Chidren's Emergency Clinical Hospital
🇷🇴Iasi, Romania
Regional Pediatric Clinical Hospital #1
🇷🇺Ekaterinburg, Russian Federation
Moscow State Institution: Morozovskaya Pediatric City Clinical Hospital
🇷🇺Moscow, Russian Federation
City of Hope National Medical Center
🇺🇸Duarte, California, United States