Tumor Lysis SyndromePhase 1/2FLORETNCT03605212
Febuxostat for Tumor Lysis Syndrome Prevention in Hematological Malignancies of Paediatric Patients and Adults
A Phase 1/2 study testing Febuxostat in people with Tumor Lysis Syndrome, run by Menarini Group at 17 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Tumor Lysis Syndrome
- What is being tested?
- Febuxostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 17 sitesin 4 countries
- Study dates
- 27 Feb 2017to 25 Jul 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
17 sites in 4 countries.
17 sites in 4 countries
Italy9 sites
SOC Oncologia Medica A - Centro di Riferimento Oncologico
Aviano, Pordenone, 33081
Policlinico S. Orsola Malpighi
Bologna, 40138
A.O.U.C. Azienda Ospedaliero - Universitaria Careggi
Florence, 50134
Azienda Ospedaliero Universitaria Meyer
Florence, 50139
Istituto G Gaslini Ospedale Pediatrico IRCCS
Genova, 16147
Azienda Ospedaliero-Universitaria Pisana
Pisa, 56126
IRCCS Ospedale Pediatrico Bambino Gesù
Rome, 00165
Ospedale Infantile Regina Margherita
Torino, 10126
Azienda Ospedaliera Universitaria Integrata di Verona
Verona, 37126
Spain4 sites
Hospital de San Pedro de Alcantara
Cáceres, 10002
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitari i Politècnic La Fe
Valencia, 46026
Hungary3 sites
Semmelweis Egyetem (paediatric)
Budapest, 1083
Semmelweis Egyetem
Budapest, 1085
Debreceni Egyetem Klinikai Központ
Debrecen, 4032
About this study
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
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.
Read the 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.
- Conditions
- Tumor Lysis Syndrome
- Being tested
- Febuxostat
- Keywords
- TLS, FLO-02, Hematological Malignancies
- Medical subject headings
- Tumor Lysis Syndrome, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FebuxostatDrug
Intervention is orally administered to patients in this arm.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Febuxostat film-coated tablets 2x20 mg/QD for 7-9 days Receives: Drug: Febuxostat |
| Cohort 2 | Experimental | Febuxostat film-coated tablets 3x20 mg/QD for 7-9 days Receives: Drug: Febuxostat |
| Cohort 3 | Experimental | Febuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) Receives: Drug: Febuxostat |
| Cohort 4 | Experimental | Febuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) Receives: Drug: Febuxostat |
| Adults | Active comparator | Febuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) Receives: Drug: Febuxostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F)
Apparent clearance of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Measured: 7 days
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)
Measured: 7 days
PK Parameter: Absorption Rate Constant (Ka)
Absorption rate constant of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Measured: 7 days
PK Parameter: Area Under Curve (AUC)
AUC of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Measured: 7 days
PK Parameter: Maximum Plasma Concentration (Cmax)
Maximum plasma concentration of febuxostat from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Measured: 7 days
PK Parameter: Tmax
Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
Measured: 7 days
Secondary outcomes (6)
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)
Measured: 8 days
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.
Measured: 7 days
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.
Measured: 7 days
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.
Measured: Estimated maximum time frame: 27 days
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.
Measured: Estimated maximum time frame: 27 days
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).
Measured: Estimated maximum time frame: 27 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2018
- Study start27 Feb 2017
- Primary completion25 Jul 2018
- Study completion25 Jul 2018
Why it stopped: The study was stopped as per EMA waiver granted on 20July2018.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tumor Lysis SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menarini Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Franco Locatelli, Prof, MD, Study chair, IRCCS Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio, 4, 00165 Rome, IT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03605212
- Sponsor's protocol ID
- FLO-02
- Other IDs
- 2016-001445-61, 2016
- Acronym
- FLORET
- Status last verified
- Jan 2019
- First submitted
- 29 May 2018
- Last updated
- 3 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03605212
- Acronym / sponsor ID
- FLORET / FLO-02
- Conditions
- Tumor Lysis Syndrome
- Keywords
- TLS, FLO-02, Hematological Malignancies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped as per EMA waiver granted on 20July2018.
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Menarini GroupIndustry (pharma, biotech, devices)
- Study start
- 27 Feb 2017 (actual)
- Primary completion
- 25 Jul 2018 (actual)
- Study completion
- 25 Jul 2018 (actual)
- First posted
- 30 Jul 2018 (actual)
- Results
- Posted 3 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: FebuxostatFebuxostat film-coated tablets 2x20 mg/QD for 7-9 days |
| Cohort 2 | Experimental | Drug: FebuxostatFebuxostat film-coated tablets 3x20 mg/QD for 7-9 days |
| Cohort 3 | Experimental | Drug: FebuxostatFebuxostat film-coated tablets 1x80 mg/QD for 7-9 days (Adenuric® 80 mg) |
| Cohort 4 | Experimental | Drug: FebuxostatFebuxostat film-coated tablets 1x120 mg/QD for 7-9 days (Adenuric® 120 mg) |
| Adults | Active comparator | Drug: FebuxostatFebuxostat film-coated tablets 120 mg/QD for 7-9 days (Adenuric® 120 mg) |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FebuxostatIntervention is orally administered to patients in this arm. | Drug | Adults, Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
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)
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)
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)
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)
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)
PK Parameter: Tmax
Time frame: 7 days
Time to Cmax from Visit 2 (Day 2) to Evaluation Visit (Visit 8, Day 8)
6 secondary outcomes
Pharmacodynamic (PD) Parameter: Area Under the Curve of Serum Uric Acid (sUA)
Time frame: 8 days
Assessment of Laboratory Tumor Lysis Syndrome (LTLS)
Time frame: 7 days
Assessment of Clinical Tumor Lysis Syndrome (CTLS)
Time frame: 7 days
Assessment of Treatment Emergent Signs and Symptoms (TESS)
Time frame: Estimated maximum time frame: 27 days
Assessment of Participants Affected by Treatment Emergent Signs and Symptoms (TESS)
Time frame: Estimated maximum time frame: 27 days
Performance Status (PS) Evaluation
Time frame: Estimated maximum time frame: 27 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Tumor Lysis Syndrome
Recruiting
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RecruitingPhase 1
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CLL / SLL, CLL (Chronic Lymphocytic Leukemia)
RecruitingPhase 3
A Study to Evaluate the Risk of Tumor Lysis Syndrome (TLS) in Adult Participants Receiving Oral Venetoclax in Combination With Intravenously Infused Obinutuzumab or Oral Acalabrutinib for Previously Untreated Chronic Lymphocytic Leukemia (CLL)
Chronic Lymphocytic Leukemia
RecruitingObservational study
Timing of Renal Replacement Therapy Initiation in Tumor Lysis Syndrome
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Franco Locatelli, Prof, MD study chair
IRCCS Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio, 4, 00165 Rome, IT
17 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Febuxostat in people with Tumor Lysis Syndrome, run by Menarini Group at 17 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Italy, Spain, Hungary, Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic (PK) Parameter: Apparent Clearance (CL/F) (time frame: 7 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2021.