Clinical trial NCT04610736: TEMOkids Study : A Phase I Pediatric Study for KIMOZO, Oral Suspension of Temozolomide
Official title: TEMOkids Study: A Population Pharmacokinetic, Acceptability and Safety Study for KIMOZO, a Paediatric Oral Suspension of Temozolomide
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Pediatric Cancer
Keywords: neuroblastoma
other pediatric cancers requiring temozolomide
Lead sponsor: Orphelia Pharma
Sponsor class: INDUSTRY
Collaborators: name: ClinSearch
First posted: 2020-10-30
Enrollment: 49
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-randomized, international, multi-centre, open-label, single arm study
Primary purpose: TREATMENT

Brief summary: Non-randomized, international, multi-centre, open-label, single arm study to determine the pharmacokinetic (PK) parameters of a single dose of an oral suspension of temozolomide (KIMOZO) in the pediatric population aged 1 year and over.

Detailed description: The TEMOkids study is an international open-label, non-randomized, prospective, single-arm phase 1 study to determine the pharmacokinetic (PK) parameters of a single dose of an oral suspension of temozolomide (KIMOZO) in the pediatric population aged 1 year and over.

Patients will be subject to at least one 21 or 28-day treatment cycle involving administration of an oral suspension of temozolomide (KIMOZO) for five consecutive days followed by 16 or 23-days resting period, with determination of the PK parameters on the first treatment day.

Five (5) additional cycles will be allowed under compassionate use regimen. The compassionate use period could be extended at the discretion of the investigator and in agreement with the sponsor. Safety and activity data will be collected during the compassionate follow-up period.

The study will be held in multiple sites spread across Europe.

Eligibility criteria: Inclusion Criteria:

* Pediatric patients in need of temozolomide (all indications with 5-day treatment per 21- or 28-day cycle).
* Male and female patients aged 1 to less than 18 years
* Patients who have signed the informed consent or for which one, both parents or legal guardian (depending on local legislation) have signed the informed consent.
* Patients having records of coverage by a health insurance
* Life expectancy ≥ 3 months
* Adequate haematological function:

  * haemoglobin ≥ 80 g/L (transfusion support authorized)
  * neutrophil count ≥ 1.0 x 10e9 cells/L
  * platelet count ≥ 100 x 10e9 cells/L (without transfusion support)
  * in case of bone marrow involvement: neutrophils ≥ 0.5 x 10e9 cells/L and platelets ≥75 x 10e9 cells/L
* Adequate renal function:

  * Creatine clearance ≥ 60 mL/min.1.73m² according to the Schwartz formula \[1\] or its modified form \[2\]
* Adequate hepatic function:

  * bilirubin ≤1.5 x ULN
  * AST and ALT ≤ 2.5 x ULN (AST, ALT 5xULN in case of liver metastases)
* Lansky Score ≥ 70%

Exclusion Criteria:

* Patients who are co-administrated at day one with sodium valproate as it decreases the clearance of temozolomide
* Patients with (naso)gastric tube administration of temozolomide during first cycle of treatment.
* Patients already enrolled in studies investigating temozolomide or other investigational new drugs.
* A post-menarche female with a positive blood/urine pregnancy test at inclusion.
* Known contraindication or hypersensitivity to temozolomide or any chemically close substance

Primary outcomes:
measure: Population Phamacokinetic parameter: AUC24
timeFrame: At Day 1 of treatment cycle 1 (each cycle is 21 or 28 days) with post-dose samples collected at about 0.15, 0.5, 1, 2.5, and 7 hours post dose
measure: Population Phamacokinetic parameter: Cmax
timeFrame: At Day 1 of treatment cycle 1 (each cycle is 21 or 28 days) with post-dose samples collected at about 0.15, 0.5, 1, 2.5, and 7 hours post dose
measure: Population Phamacokinetic parameter: T1/2
timeFrame: At Day 1 of treatment cycle 1 (each cycle is 21 or 28 days) with post-dose samples collected at about 0.15, 0.5, 1, 2.5, and 7 hours post dose
Secondary outcomes:
measure: Acceptability of the oral suspension of temozolomide: score
timeFrame: At Day 1 and Day 5 of treatment cycle 1 (each cycle is 21 or 28 days)
measure: Incidence of treatment-emergent adverse events
timeFrame: Through study completion, an average of 6 months including compassionate use period
measure: Activity of the oral suspension of temozolomide
timeFrame: At the end of each 21- or 28-day treatment cycle of the compassionate use period
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Institut d'Hématologie et d'Oncologie Pédiatrique
city: Marseille
country: France
facility: CHU Timone Enfants
city: Paris
country: France
facility: Institut Curie
city: Villejuif
country: France
facility: Gustave Roussy
city: Berlin
country: Germany
facility: Charité University Medicine Berlin
city: Heidelberg
country: Germany
facility: Hopp Children's Cancer Center Heidelberg
city: Utrecht
country: Netherlands
facility: Princess Maxima Center for Pediatric Oncology
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Samuel Abbou, MD
role: PRINCIPAL_INVESTIGATOR
References: