Efficacy and Safety of Palonosetron Intravenous in Prevention of Chemotherapy Induced Nausea and Vomiting in Pediatric Patients

Chemotherapy-Induced Nausea and Vomiting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01442376
• Other study ID #: PALO-10-20
• Status: Completed
• Phase: Phase 3
• First received: September 21, 2011
• Last updated: August 4, 2014
• Start date: September 2011
• Est. completion date: November 2012

Study information

• Verified date: August 2014
• Source: Helsinn Healthcare SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationHungary: National Institute of PharmacyBulgaria: Bulgarian Drug AgencySerbia and Montenegro: Agency for Drugs and Medicinal DevicesEstonia: The State Agency of MedicineCzech Republic: State Institute for Drug ControlAustria: Federal Office for Safety in Health CareChile: Instituto de Salud Pública de ChileRomania: State Institute for Drug ControlRussia: Ministry of Health of the Russian FederationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaUkraine: Ministry of HealthGermany: Ministry of HealthPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPeru: Instituto Nacional de SaludFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 502
• Est. completion date: November 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 16 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Chemotherapy-Induced Nausea and Vomiting
• Nausea
• Vomiting

Intervention

Drug:
• Palonosetron
Single dose Palonosetron IV 10 mcg/kg up to a maximum total dose of 0.75 mg
• Palonosetron
Single dose Palonosetron IV 20 mcg/kg up to a maximum total dose of 1.5 mg
• Ondansetron
Single three (every 4 hours) Ondansetron IV doses 0.15 mg/kg up to a maximum total dose of 32 mg
• Placebo to Ondansetron

• Placebo to Ondansetron

• Placebo to Palonosetron

Locations

Country	Name	City	State
Argentina	CEMIC	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Hospital Privado Centro Medico de Cordoba	Cordoba
Argentina	Hospital Nacional "Prof. Dr. Alejandro Posadas"	El Palomar
Austria	Children's Cancer Research Institute	Wien
Austria	Medical University of Vienna	Wien
Bulgaria	Pediatrics and Genetic Medicine Clinic	Plovdiv
Bulgaria	Specialised Hospital for Active Treatment of Oncohematological Diseases in Children	Sofia
Bulgaria	Specialised Pediatric Clinic of Clinical Hematology and Oncology Mutiprofile Hospital for Active Treatment "Sveta Marina"	Varna
Chile	Clinica Davila	Santiago
Chile	Clinica Santa Maria SA	Santiago
Chile	Hospital Clinico UC	Santiago
Chile	Hospital Dr Luis Calvo Mackenna	Santiago
Czech Republic	University Hospital Brno, Children's Medical Centre, Clinic of Pediatric Oncology	Brno
Czech Republic	University Hospital in Ostrava, Clinic of Pediatric	Ostrava
Czech Republic	University Hospital in Pilsen	Plzen-Lochotin
Czech Republic	University Hospital Motol, Department of Paediatric Heamatology and Oncology	Praha 5
Estonia	Tallin Children's Hospital	Tallinn
Estonia	Tartu University Hospital, Hematology - Oncology Clinic	Tartu
France	CHRU de Lille - Hopital d'Hematologie Pediatrique	Lille Cedex
France	Hopital Arnaud de Villenueve	Montpellier
France	CHRU de Tours - Centre de Pediatrie Gatien de Clocheville	Tours Cedex 09
Germany	University Hospital of Cologne	Cologne
Germany	University Medical Center Freiburg	Freiburg
Hungary	Semmelweis University, 2nd Department of Pediatrics	Budapest
Hungary	University of Szeged, Szent-Gyorgyl Albert Clinical Center, Department of Pediatrics	Szeged
Peru	Instituto Nacional de Enfermedades Neoplásicas	Lima
Peru	Oncosalud SAC RCI 300	Lima
Peru	Clinica Anglo Americana - Centro de Investigacion Oncologica CAA	San Isidro Lima
Poland	Szpital Uniwersytecki - Department of Pediatrics, Hematology and Oncology	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital	Lodz
Poland	Dzieciecy Szpital Kliniczny	Lublin
Poland	Institut Pomnik - The Children Memorial Health Institute, Department of Oncology	Warsaw
Poland	Samodzielny Publiczny Szpital	Wroclaw
Romania	"Prof. Dr. Alexandru Trestioreanu" Institute of Oncology, Pediatric Oncology Department	Bucharest
Romania	Fundeni Clinical Institute, Pediatrics Clinic	Bucharest
Romania	"Prof. Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca Pediatric Department	Cluj
Romania	Sf. Maria - Chidren's Emergency Clinical Hospital	Iasi
Russian Federation	Chelyabinsk Pediatric Regional Clinical Hospital, Oncohematology Department	Chelyabinsk
Russian Federation	Regional Pediatric Clinical Hospital #1	Ekaterinburg
Russian Federation	Pediatric Regional Clinical Hospital	Krasnodar
Russian Federation	Moscow State Institution: Morozovskaya Pediatric City Clinical Hospital	Moscow
Russian Federation	Russian Oncology Research Center	Moscow
Russian Federation	Omsk Regional Clinical Oncology Center	Omsk
Russian Federation	St. Petersburg State Medical University	St. Petersburg
Russian Federation	State Clinical Hospital	St. Petersburg
Serbia	Department for hematology and oncology	Belgrade
Serbia	Clinical Center Nis, Clinic for pediatrics internal diseases, Department for hematology and oncology	Nis
Ukraine	Public Treatment and Prophylaxis Institution: Regional Children's Clinical Hospital	Donetsk
Ukraine	State Institution: V. K. Husak Institute of Urgent and Reconstructive Surgery	Donetsk
Ukraine	Public Healthcare Institution: Regional Children's Clinical Hospital #1	Kharkiv
Ukraine	National Institute of Cancer	Kyiv
United States	The Children's Hospital	Aurora	Colorado
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	City of Hope National Medical Center	Duarte	California
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	University of Kentucky - Chandler Medical Center	Lexington	Kentucky
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Nemours Children's Clinic-Orlando	Orlando	Florida
United States	Nemours Children's Clinic	Pensacola	Florida
United States	Backus Children's Hospital at University Pediatrics	Savannah	Georgia
United States	Upstate Medical University	Syracuse	New York
United States	Department of Pediatrics	Valhalla	New York
United States	A. I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Helsinn Healthcare SA

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Bulgaria,  Chile,  Czech Republic,  Estonia,  France,  Germany,  Hungary,  Peru,  Poland,  Romania,  Russian Federation,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With Complete Response 0 to 24 Hours (Acute Phase) in Cycle 1	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.	0 to 24 hours after T0	No
Secondary	Proportion of Patients With Complete Response >24 to 120 Hours (Delayed Phase) in Cycle 1	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.	from >24 to 120 hours (delayed phase) after T0	No