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

NCT ID: NCT01442376

Last Updated: 2014-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 502 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2012-11-30

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.

Conditions

Chemotherapy-Induced Nausea and Vomiting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Palonosetron 10 mcg/kg

Palonosetron and placebo to Ondansetron

Intervention:

Drug: Palonosetron

Group Type: EXPERIMENTAL

Palonosetron

Intervention Type: DRUG

Single dose Palonosetron IV 10 mcg/kg up to a maximum total dose of 0.75 mg

Placebo to Ondansetron

Intervention Type: DRUG

Palonosetron 20 mcg/kg

Palonosetron and placebo to Ondansetron

Intervention:

Drug: Palonosetron

Group Type: EXPERIMENTAL

Palonosetron

Intervention Type: DRUG

Single dose Palonosetron IV 20 mcg/kg up to a maximum total dose of 1.5 mg

Placebo to Ondansetron

Intervention Type: DRUG

Ondansetron

Ondansetron and placebo to Palonosetron

Drug:

Comparator: Ondansetron

Group Type: ACTIVE_COMPARATOR

Ondansetron

Intervention Type: DRUG

Single three (every 4 hours) Ondansetron IV doses 0.15 mg/kg up to a maximum total dose of 32 mg

Placebo to Palonosetron

Intervention Type: DRUG

Interventions

Palonosetron

Single dose Palonosetron IV 10 mcg/kg up to a maximum total dose of 0.75 mg

Intervention Type: DRUG

Palonosetron

Single dose Palonosetron IV 20 mcg/kg up to a maximum total dose of 1.5 mg

Intervention Type: DRUG

Ondansetron

Single three (every 4 hours) Ondansetron IV doses 0.15 mg/kg up to a maximum total dose of 32 mg

Intervention Type: DRUG

Placebo to Ondansetron

Intervention Type: DRUG

Placebo to Ondansetron

Intervention Type: DRUG

Placebo to Palonosetron

Intervention Type: DRUG

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

• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helsinn Healthcare SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

City of Hope National Medical Center

Duarte, California, United States

The Children's Hospital

Aurora, Colorado, United States

A. I. duPont Hospital for Children

Wilmington, Delaware, United States

Nemours Children's Clinic

Jacksonville, Florida, 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

University of Kentucky - Chandler Medical Center

Lexington, Kentucky, United States

Upstate Medical University

Syracuse, New York, United States

Department of Pediatrics

Valhalla, New York, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

CEMIC

Buenos Aires, , Argentina

Hospital Privado Centro Medico de Cordoba

Córdoba, , Argentina

Hospital Nacional "Prof. Dr. Alejandro Posadas"

El Palomar, , Argentina

Children's Cancer Research Institute

Vienna, , Austria

Medical University of Vienna

Vienna, , Austria

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, , Bulgaria

Hospital Dr Luis Calvo Mackenna

Santiago, , Chile

Clinica Santa Maria SA

Santiago, , Chile

Hospital Clinico UC

Santiago, , Chile

Clinica Davila

Santiago, , Chile

University Hospital Brno, Children's Medical Centre, Clinic of Pediatric Oncology

Brno, , Czechia

University Hospital in Ostrava, Clinic of Pediatric

Ostrava, , Czechia

University Hospital in Pilsen

Plzen-Lochotin, , Czechia

University Hospital Motol, Department of Paediatric Heamatology and Oncology

Prague, , Czechia

Tallin Children's Hospital

Tallinn, , Estonia

Tartu University Hospital, Hematology - Oncology Clinic

Tartu, , Estonia

CHRU de Lille - Hopital d'Hematologie Pediatrique

Lille, , France

Hopital Arnaud de Villenueve

Montpellier, , France

CHRU de Tours - Centre de Pediatrie Gatien de Clocheville

Tours, , France

University Hospital of Cologne

Cologne, , Germany

University Medical Center Freiburg

Freiburg im Breisgau, , Germany

Semmelweis University, 2nd Department of Pediatrics

Budapest, , Hungary

University of Szeged, Szent-Gyorgyl Albert Clinical Center, Department of Pediatrics

Szeged, , Hungary

Instituto Nacional de Enfermedades Neoplásicas

Lima, , Peru

Oncosalud SAC RCI 300

Lima, , Peru

Clinica Anglo Americana - Centro de Investigacion Oncologica CAA

San Isidro Lima, , Peru

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, , Poland

Fundeni Clinical Institute, Pediatrics Clinic

Bucharest, , Romania

"Prof. Dr. Alexandru Trestioreanu" Institute of Oncology, Pediatric Oncology Department

Bucharest, , Romania

"Prof. Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca Pediatric Department

Cluj-Napoca, , Romania

Sf. Maria - Chidren's Emergency Clinical Hospital

Iași, , Romania

Chelyabinsk Pediatric Regional Clinical Hospital, Oncohematology Department

Chelyabinsk, , Russia

Pediatric Regional Clinical Hospital

Krasnodar, , Russia

Russian Oncology Research Center

Moscow, , Russia

Moscow State Institution: Morozovskaya Pediatric City Clinical Hospital

Moscow, , Russia

Omsk Regional Clinical Oncology Center

Omsk, , Russia

St. Petersburg State Medical University

Saint Petersburg, , Russia

State Clinical Hospital

Saint Petersburg, , Russia

Regional Pediatric Clinical Hospital #1

Yekaterinburg, , Russia

Department for hematology and oncology

Belgrade, , Serbia

Clinical Center Nis, Clinic for pediatrics internal diseases, Department for hematology and oncology

Niš, , Serbia

State Institution: V. K. Husak Institute of Urgent and Reconstructive Surgery

Donetsk, , Ukraine

Public Treatment and Prophylaxis Institution: Regional Children's Clinical Hospital

Donetsk, , Ukraine

Public Healthcare Institution: Regional Children's Clinical Hospital #1

Kharkiv, , Ukraine

National Institute of Cancer

Kyiv, , Ukraine

Countries

United States; Argentina; Austria; Bulgaria; Chile; Czechia; Estonia; France; Germany; Hungary; Peru; Poland; Romania; Russia; Serbia; Ukraine

References

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.

Reference Type: DERIVED

PMID: 26795844 (View on PubMed)

Other Identifiers

PALO-10-20

Identifier Type: -

Identifier Source: org_study_id