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

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ClinicalTrials.gov Identifier: NCT03605212
Recruitment Status : Recruiting
First Posted : July 30, 2018
Last Update Posted : July 30, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Tumor Lysis Syndrome Drug: Febuxostat Phase 1 Phase 2

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 will 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
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
Study Start Date : November 2016
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Febuxostat

Arm Intervention/treatment
Experimental: Cohort 1
Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days
Drug: Febuxostat
Experimental: Cohort 2
Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days
Drug: Febuxostat
Experimental: Cohort 3
Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg)
Drug: Febuxostat
Experimental: Cohort 4
Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg)
Drug: Febuxostat
Active Comparator: Adults
Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg)
Drug: Febuxostat



Primary Outcome Measures :
  1. Pharmacokinetic (PK) parameter: apparent clearance (CL/F) [ Time Frame: 7 days ]
    Apparent clearance of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

  2. PK parameter: apparent volume of distribution (Vd/F) [ Time Frame: 7 days ]
    Apparent volume of distribution of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

  3. PK parameter: absorption rate constant (Ka) [ Time Frame: 7 days ]
    Absorption rate constant of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

  4. PK parameter: area under curve (AUC) [ Time Frame: 7 days ]
    AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

  5. PK parameter: maximum plasma concentration (Cmax) [ Time Frame: 7 days ]
    Maximum plasma concentration of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)

  6. PK parameter: Tmax [ Time Frame: 7 days ]
    Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)


Secondary Outcome Measures :
  1. Pharmacodynamic (PD) parameter: area under the curve of serum uric acid (sUA) [ Time Frame: 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)

  2. Assessment of Laboratory Tumor Lysis Syndrome (LTLS) [ Time Frame: 8 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.

  3. Assessment of Clinical Tumor Lysis Syndrome (CTLS) [ Time Frame: 8 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.

  4. Assessment of Treatment Emergent Signs and Symptoms (TESS) [ Time Frame: 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 are assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. An adverse event is considered as TESS if it occurs for the first time or if it worsens in terms of seriousness or severity after first study drug intake.

  5. Performance Status (PS) Evaluation [ Time Frame: Estimated maximum time frame: 27 days ]
    Quality of life will be assessed by PS evaluation from Screening Visit to End of Study Visit. The Karnofsky Performance Status (KPS) scale will be used for patients aged 16 years and older; the Lansky Play Performance Status (LPS) scale will 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).



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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03605212


Contacts
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Contact: Angela Capriati, Corporate Director of Clinical +39 055 5680 ext 9990 acapriati@menarini-ricerche.it
Contact: Silvia Manunta, Clinical Research Physician +39 055 5680 ext 9520 smanunta@menarini-ricerche.it

Locations
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Bulgaria
University Hospital Tsaritsa Yoanna Not yet recruiting
Sofia, Bulgaria, 1527
Hungary
Semmelweis Egyetem (paediatric) Not yet recruiting
Budapest, Hungary, 1083
Semmelweis Egyetem Recruiting
Budapest, Hungary, 1085
Debreceni Egyetem Klinikai Központ Terminated
Debrecen, Hungary, 4032
Italy
SOC Oncologia Medica A - Centro di Riferimento Oncologico Recruiting
Aviano, Pordenone, Italy, 33081
Policlinico S. Orsola Malpighi Recruiting
Bologna, Italy, 40138
A.O.U.C. Azienda Ospedaliero - Universitaria Careggi Not yet recruiting
Firenze, Italy, 50134
Azienda Ospedaliero Universitaria Meyer Not yet recruiting
Firenze, Italy, 50139
Istituto G Gaslini Ospedale Pediatrico IRCCS Not yet recruiting
Genova, Italy, 16147
Azienda Ospedaliero-Universitaria Pisana Terminated
Pisa, Italy, 56126
IRCCS Ospedale Pediatrico Bambino Gesù Not yet recruiting
Rome, Italy, 00165
Ospedale Infantile Regina Margherita Recruiting
Torino, Italy, 10126
Azienda Ospedaliera Universitaria Integrata di Verona Not yet recruiting
Verona, Italy, 37126
Spain
Hospital de San Pedro de Alcantara Recruiting
Caceres, Spain, 10002
Hospital General Universitario Gregorio Maranon Recruiting
Madrid, Spain, 28007
Hospital Universitario La Paz Not yet recruiting
Madrid, Spain, 28046
Hospital Universitari i Politècnic La Fe Recruiting
Valencia, Spain, 46026
Sponsors and Collaborators
Menarini Group
Investigators
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Study Chair: Franco Locatelli, Professor, MD IRCCS Ospedale Pediatrico Bambino Gesù Department of Pediatric Hematology and Oncology Piazza Sant'Onofrio, 4, 00165 Rome, Italy

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Responsible Party: Menarini Group
ClinicalTrials.gov Identifier: NCT03605212     History of Changes
Other Study ID Numbers: FLO-02
2016-001445-61 ( EudraCT Number )
First Posted: July 30, 2018    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Menarini Group:
TLS
FLO-02
Hematological Malignancies

Additional relevant MeSH terms:
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Febuxostat
Syndrome
Tumor Lysis Syndrome
Disease
Pathologic Processes
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gout Suppressants
Antirheumatic Agents