TEMOkids Study : A Phase I Pediatric Study for KIMOZO, Oral Suspension of Temozolomide

Study Overview
=================
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.

Official Title
-----------------
TEMOkids Study: A Population Pharmacokinetic, Acceptability and Safety Study for KIMOZO, a Paediatric Oral Suspension of Temozolomide

Conditions
-----------------
Pediatric Cancer

Intervention / Treatment
-----------------
* Drug: Temozolomide Oral Suspension


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Non-randomized, international, multi-centre, open-label, single arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single arm<br>Temozolomide 40 mg/ml, Oral suspension | Drug: Temozolomide Oral Suspension<br>* One prescribed oral dose (range 75 to 200 mg/m2) once daily for 5 days<br>* Other names: KIMOZO, Ped-TMZ;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Population Phamacokinetic parameter: AUC24 | Estimated by a population analysis performed with NONMEM (7.4) | 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 | 
| Population Phamacokinetic parameter: Cmax | Estimated by a population analysis performed with NONMEM (7.4) | 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 | 
| Population Phamacokinetic parameter: T1/2 | Estimated by a population analysis performed with NONMEM (7.4) | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability of the oral suspension of temozolomide: score | Scoring with a standardized assessment tool: CAST - ClinSearch Acceptability Score Test®. This tool measures 9 observational drivers of drug acceptability. | At Day 1 and Day 5 of treatment cycle 1 (each cycle is 21 or 28 days) | 
| Incidence of treatment-emergent adverse events | Adverse events collected directly by investigators when patient is hospitalized and through patient diary completed by caregivers and medically controlled by investigators when patient is at home | Through study completion, an average of 6 months including compassionate use period | 
| Activity of the oral suspension of temozolomide | Activity assessment (complete or partial response, stable disease, disease progression) | At the end of each 21- or 28-day treatment cycle of the compassionate use period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
neuroblastoma, other pediatric cancers requiring temozolomide