Febuxostat for Tumor Lysis Syndrome Prevention in Hematological Malignancies of Paediatric Patients and Adults
- Registration Number
- NCT03605212
- Lead Sponsor
- Menarini Group
- Brief 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.
- Detailed 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 & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 30
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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 3 Febuxostat Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Cohort 4 Febuxostat Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Adults Febuxostat Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Cohort 1 Febuxostat Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Cohort 2 Febuxostat Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days
- Primary Outcome Measures
Name Time Method Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F) 7 days Apparent clearance of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
PK Parameter: Absorption Rate Constant (Ka) 7 days Absorption rate constant of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
PK Parameter: Area Under Curve (AUC) 7 days AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
PK Parameter: Maximum Plasma Concentration (Cmax) 7 days Maximum plasma concentration of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
PK Parameter: Apparent Volume of Distribution (Vd/F) 7 days Apparent volume of distribution of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
PK Parameter: Tmax 7 days Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
- Secondary Outcome Measures
Name Time Method Assessment of Clinical Tumor Lysis Syndrome (CTLS) 7 days 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.
Assessment of Treatment Emergent Signs and Symptoms (TESS) Estimated maximum time frame: 27 days 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.
Pharmacodynamic (PD) Parameter: Area Under the Curve of Serum Uric Acid (sUA) 8 days Area under the curve of sUA from baseline (Visit 1, Day 1) to the Evaluation Visit (Visit 8, Day 8) (AUC sUA 1-8)
Assessment of Laboratory Tumor Lysis Syndrome (LTLS) 7 days 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.
Assessment of Participants Affected by Treatment Emergent Signs and Symptoms (TESS) Estimated maximum time frame: 27 days Number of participants affected by TESS from Screening Visit to End of Study Visit.
Performance Status (PS) Evaluation Estimated maximum time frame: 27 days 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).
Trial Locations
- Locations (17)
Debreceni Egyetem Klinikai Központ
🇭🇺Debrecen, Hungary
Ospedale Infantile Regina Margherita
🇮🇹Torino, Italy
Istituto G Gaslini Ospedale Pediatrico IRCCS
🇮🇹Genova, Italy
University Hospital Tsaritsa Yoanna
🇧🇬Sofia, Bulgaria
Hospital de San Pedro de Alcantara
🇪🇸Caceres, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Semmelweis Egyetem (paediatric)
🇭🇺Budapest, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
SOC Oncologia Medica A - Centro di Riferimento Oncologico
🇮🇹Aviano, Pordenone, Italy
A.O.U.C. Azienda Ospedaliero - Universitaria Careggi
🇮🇹Firenze, Italy
Policlinico S. Orsola Malpighi
🇮🇹Bologna, Italy
Azienda Ospedaliero Universitaria Meyer
🇮🇹Firenze, Italy
IRCCS Ospedale Pediatrico Bambino Gesù
🇮🇹Rome, Italy
Azienda Ospedaliera Universitaria Integrata di Verona
🇮🇹Verona, Italy
Azienda Ospedaliero-Universitaria Pisana
🇮🇹Pisa, Italy
Hospital Universitari i Politècnic La Fe
🇪🇸Valencia, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain