Febuxostat for Tumor Lysis Syndrome Prevention in Hematological Malignancies of Paediatric Patients and Adults

Tumor Lysis Syndrome Clinical Trial

— FLORET  

Official title:

Open Label, Multi-centre, Parallel Group Study to Compare the Pharmacokinetics (PK), Pharmacodynamics (PD) and Safety of Febuxostat Between Pediatric Patients (≥6<18 Years of Age) and Adults

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03605212
• Other study ID #: FLO-02
• Secondary ID: 2016-001445-61
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 27, 2017
• Est. completion date: July 25, 2018

Study information

• Verified date: January 2019
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the exposure of febuxostat in pediatric patients (≥6<18 years of age) and in adults suffering from hematological malignancies at intermediate to high risk of TLS and to compare the effect in terms of serum uric acid levels.

Description:

In the FLORET study it is planned to enroll 3 groups of patients in order to receive oral administration (film-coated tablets) of two different dose levels of febuxostat: children (from 6 to less than 12 years of age) will receive two different dose levels respectively; adolescents (from 12 to less than 18 years of age) will receive 80 and 120 mg/day respectively and adults (equal or major than 18 years of age) will receive 120 mg/day. The two dose levels for children and adolescents groups were to be sequentially administered, whereas the groups that will receive the first dose levels will simultaneously start the treatment at the study beginning. The individual treatment duration will be of 7 to 9 days, according to chemotherapy duration, as per Investigator's judgement.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: July 25, 2018
• Est. primary completion date: July 25, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

male and female children of 6 to less than 12 years of age, adolescents of 12 to less than

18 years of age and adults from 18 years:

• scheduled for first cytotoxic chemotherapy cycle because of hematologic malignancies
• and at intermediate or high risk of TLS
• and with no access to rasburicase

Exclusion Criteria:

• patients with contraindications as per febuxostat summary of product characteristics
• patients with severe renal insufficiency
• patients with severe hepatic insufficiency
• patients with diagnosis of Laboratory TLS (LTLS) or Clinical TLS (CTLS)

Related Conditions & MeSH terms

• Syndrome
• Tumor Lysis Syndrome

Intervention

Drug:
• Febuxostat
Intervention is orally administered to patients in this arm.

Locations

Country	Name	City	State
Bulgaria	University Hospital Tsaritsa Yoanna	Sofia
Hungary	Semmelweis Egyetem	Budapest
Hungary	Semmelweis Egyetem (paediatric)	Budapest
Hungary	Debreceni Egyetem Klinikai Központ	Debrecen
Italy	SOC Oncologia Medica A - Centro di Riferimento Oncologico	Aviano	Pordenone
Italy	Policlinico S. Orsola Malpighi	Bologna
Italy	A.O.U.C. Azienda Ospedaliero - Universitaria Careggi	Firenze
Italy	Azienda Ospedaliero Universitaria Meyer	Firenze
Italy	Istituto G Gaslini Ospedale Pediatrico IRCCS	Genova
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Italy	IRCCS Ospedale Pediatrico Bambino Gesù	Rome
Italy	Ospedale Infantile Regina Margherita	Torino
Italy	Azienda Ospedaliera Universitaria Integrata di Verona	Verona
Spain	Hospital de San Pedro de Alcantara	Caceres
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitari i Politècnic La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Countries where clinical trial is conducted

Bulgaria,  Hungary,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F)	Apparent clearance of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)	7 days
Primary	PK Parameter: Apparent Volume of Distribution (Vd/F)	Apparent volume of distribution of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)	7 days
Primary	PK Parameter: Absorption Rate Constant (Ka)	Absorption rate constant of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)	7 days
Primary	PK Parameter: Area Under Curve (AUC)	AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)	7 days
Primary	PK Parameter: Maximum Plasma Concentration (Cmax)	Maximum plasma concentration of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)	7 days
Primary	PK Parameter: Tmax	Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)	7 days
Secondary	Pharmacodynamic (PD) Parameter: Area Under the Curve of Serum Uric Acid (sUA)	Area under the curve of sUA from baseline (Visit 1, Day 1) to the Evaluation Visit (Visit 8, Day 8) (AUC sUA 1-8)	8 days
Secondary	Assessment of Laboratory Tumor Lysis Syndrome (LTLS)	Assessment of LTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). LTLS is diagnosed if levels of 2 or more values of uric acid, potassium, phosphate or calcium are more than or less than normal at presentation or if they change by at least 25% from baseline.	7 days
Secondary	Assessment of Clinical Tumor Lysis Syndrome (CTLS)	Assessment of CTLS at Visit 1 (Day 1) and from Start of Chemotherapy (Visit 3, Day 3) to the Evaluation Visit (Visit 8, Day 8). CTLS is present when LTLS is accompanied by at least one of the following significant clinical complications: increased creatinine level = 1.5 upper limit of normal, cardiac arrhythmia/sudden death or seizure.	7 days
Secondary	Assessment of Treatment Emergent Signs and Symptoms (TESS)	Assessment of incidence, severity (through Mild/Moderate/Severe scale), seriousness and treatment-causality of TESS from Screening Visit to End of Study Visit. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. An adverse event was considered as TESS if it occured for the first time or if it worsened in terms of seriousness or severity after first study drug intake.	Estimated maximum time frame: 27 days
Secondary	Assessment of Participants Affected by Treatment Emergent Signs and Symptoms (TESS)	Number of participants affected by TESS from Screening Visit to End of Study Visit.	Estimated maximum time frame: 27 days
Secondary	Performance Status (PS) Evaluation	Quality of life was to be assessed by PS evaluation from Screening Visit to End of Study Visit. The Karnofsky Performance Status (KPS) scale was to be used for patients aged 16 years and older; the Lansky Play Performance Status (LPS) scale was to be used for patients aged less than 16 years. Both scales range from scores of 0 to 100 points at intervals of 10 where 0 points represent the worst outcome (KPS: 0 = death; LPS: 0 = unresponsive) and 100 points the best (KPS: 100 = normal, no complaints, no evidence of disease; LPS: 100 = fully active).	Estimated maximum time frame: 27 days