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

NCT01442376 | Completed Phase 3 Results DMC

• 1 other identifier: PALO-10-20
• Study Type: interventional
• Target: 502
• Locations: 16 countries
• Sites: 67

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.

Conditions

Chemotherapy-Induced Nausea and Vomiting

Keywords

Prevention of Chemotherapy-Induced Nausea and Vomiting; Palonosetron; Ondansetron; Pediatric

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Proportion of Patients With Complete Response >24 to 120 Hours (Delayed Phase) in Cycle 1

  from >24 to 120 hours (delayed phase) after T0

Study Arms (3)

Palonosetron 10 mcg/kg

EXPERIMENTAL

Palonosetron and placebo to Ondansetron Intervention: Drug: Palonosetron

Drug: Palonosetron; Drug: Placebo to Ondansetron

Palonosetron 20 mcg/kg

EXPERIMENTAL

Palonosetron and placebo to Ondansetron Intervention: Drug: Palonosetron

Drug: Palonosetron; Drug: Placebo to Ondansetron

Ondansetron

ACTIVE COMPARATOR

Ondansetron and placebo to Palonosetron Drug: Comparator: Ondansetron

Drug: Ondansetron; Drug: Placebo to Palonosetron

Interventions

Palonosetron DRUG

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

Palonosetron 10 mcg/kg

Ondansetron DRUG

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

Ondansetron

Placebo to Ondansetron DRUG

Palonosetron 10 mcg/kg

Placebo to Palonosetron DRUG

Ondansetron

Eligibility Criteria

• Age: Up to 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• 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);

Sponsors & Collaborators

• Helsinn Healthcare SA: lead

Study Sites (67)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

A. I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

Nemours Children's Clinic-Orlando

Orlando, Florida, 32806, United States

Location

Nemours Children's Clinic

Pensacola, Florida, 32504, United States

Location

Backus Children's Hospital at University Pediatrics

Savannah, Georgia, 31404, United States

Location

University of Kentucky - Chandler Medical Center

Lexington, Kentucky, 40536, United States

Location

Upstate Medical University

Syracuse, New York, 13210, United States

Location

Department of Pediatrics

Valhalla, New York, 10595, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1181ACH, Argentina

Location

CEMIC

Buenos Aires, C1431FWO, Argentina

Location

Hospital Privado Centro Medico de Cordoba

Córdoba, X5016KEH, Argentina

Location

Hospital Nacional "Prof. Dr. Alejandro Posadas"

El Palomar, 1684, Argentina

Location

Children's Cancer Research Institute

Vienna, 1090, Austria

Location

Medical University of Vienna

Vienna, 1090, Austria

Location

Pediatrics and Genetic Medicine Clinic

Plovdiv, 4002, Bulgaria

Location

Specialised Hospital for Active Treatment of Oncohematological Diseases in Children

Sofia, 1527, Bulgaria

Location

Specialised Pediatric Clinic of Clinical Hematology and Oncology Mutiprofile Hospital for Active Treatment "Sveta Marina"

Varna, 9010, Bulgaria

Location

Hospital Dr Luis Calvo Mackenna

Santiago, 750053, Chile

Location

Clinica Santa Maria SA

Santiago, 7520378, Chile

Location

Hospital Clinico UC

Santiago, 8330024, Chile

Location

Clinica Davila

Santiago, 8431657, Chile

Location

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

Brno, 625 00, Czechia

Location

University Hospital in Ostrava, Clinic of Pediatric

Ostrava, 708 52, Czechia

Location

University Hospital in Pilsen

Plzen-Lochotin, 304 60, Czechia

Location

University Hospital Motol, Department of Paediatric Heamatology and Oncology

Prague, 150 06, Czechia

Location

Tallin Children's Hospital

Tallinn, 13419, Estonia

Location

Tartu University Hospital, Hematology - Oncology Clinic

Tartu, 51014, Estonia

Location

CHRU de Lille - Hopital d'Hematologie Pediatrique

Lille, 59037, France

Location

Hopital Arnaud de Villenueve

Montpellier, 34295, France

Location

CHRU de Tours - Centre de Pediatrie Gatien de Clocheville

Tours, 37044, France

Location

University Hospital of Cologne

Cologne, 50924, Germany

Location

University Medical Center Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Semmelweis University, 2nd Department of Pediatrics

Budapest, H-1094, Hungary

Location

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

Szeged, H-6720, Hungary

Location

Instituto Nacional de Enfermedades Neoplásicas

Lima, 34, Peru

Location

Oncosalud SAC RCI 300

Lima, Lima 41, Peru

Location

Clinica Anglo Americana - Centro de Investigacion Oncologica CAA

San Isidro Lima, 27, Peru

Location

Szpital Uniwersytecki - Department of Pediatrics, Hematology and Oncology

Bydgoszcz, 85-094, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Uniwersytecki Szpital

Lodz, 91-378, Poland

Location

Dzieciecy Szpital Kliniczny

Lublin, 20-093, Poland

Location

Institut Pomnik - The Children Memorial Health Institute, Department of Oncology

Warsaw, 04-730, Poland

Location

Samodzielny Publiczny Szpital

Wroclaw, 50-368, Poland

Location

Fundeni Clinical Institute, Pediatrics Clinic

Bucharest, 022328, Romania

Location

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

Bucharest, 022338, Romania

Location

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

Cluj-Napoca, 400015, Romania

Location

Sf. Maria - Chidren's Emergency Clinical Hospital

Iași, 700309, Romania

Location

Chelyabinsk Pediatric Regional Clinical Hospital, Oncohematology Department

Chelyabinsk, 454076, Russia

Location

Pediatric Regional Clinical Hospital

Krasnodar, 350007, Russia

Location

Russian Oncology Research Center

Moscow, 115478, Russia

Location

Moscow State Institution: Morozovskaya Pediatric City Clinical Hospital

Moscow, 119049, Russia

Location

Omsk Regional Clinical Oncology Center

Omsk, 644013, Russia

Location

St. Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

State Clinical Hospital

Saint Petersburg, 197110, Russia

Location

Regional Pediatric Clinical Hospital #1

Yekaterinburg, 620149, Russia

Location

Department for hematology and oncology

Belgrade, 11000, Serbia

Location

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

Niš, 18000, Serbia

Location

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

Donetsk, 83045, Ukraine

Location

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

Donetsk, 83052, Ukraine

Location

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

Kharkiv, 61051, Ukraine

Location

National Institute of Cancer

Kyiv, 03022, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 26795844 DERIVED

MeSH Terms

Conditions

Vomiting

Interventions

Palonosetron; Ondansetron

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Carbazoles; Indoles; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Spinelli Tulla
• Organization: Helsinn Healthcare SA

tulla.spinelli@helsinn.com

+4191985 21 21

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2011
• First Posted: September 28, 2011
• Study Start: September 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: November 1, 2012
• Last Updated: August 7, 2014
• Results First Posted: July 28, 2014

Record last verified: 2014-08

Locations

CZ (4); SE (2); ES (2); HU (2); PE (3); AU (2); UA (4); RO (4); AR (4); FR (3); US (14); BU (3); PL (6); RU (8); CL (4); DE (2)