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

Phase 1
Active, not recruiting
Conditions
Pediatric Cancer
Interventions
Registration Number
NCT04610736
Lead Sponsor
Orphelia Pharma
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
49
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Single armTemozolomide Oral SuspensionTemozolomide 40 mg/ml, Oral suspension
Primary Outcome Measures
NameTimeMethod
Population Phamacokinetic parameter: T1/2At 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

Estimated by a population analysis performed with NONMEM (7.4)

Population Phamacokinetic parameter: AUC24At 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

Estimated by a population analysis performed with NONMEM (7.4)

Population Phamacokinetic parameter: CmaxAt 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

Estimated by a population analysis performed with NONMEM (7.4)

Secondary Outcome Measures
NameTimeMethod
Acceptability of the oral suspension of temozolomide: scoreAt Day 1 and Day 5 of treatment cycle 1 (each cycle is 21 or 28 days)

Scoring with a standardized assessment tool: CAST - ClinSearch Acceptability Score Test®. This tool measures 9 observational drivers of drug acceptability.

Incidence of treatment-emergent adverse eventsThrough study completion, an average of 6 months including compassionate use period

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

Activity of the oral suspension of temozolomideAt the end of each 21- or 28-day treatment cycle of the compassionate use period

Activity assessment (complete or partial response, stable disease, disease progression)

Trial Locations

Locations (11)

Princess Maxima Center for Pediatric Oncology

🇳🇱

Utrecht, Netherlands

Institut Curie

🇫🇷

Paris, France

Institut d'Hématologie et d'Oncologie Pédiatrique

🇫🇷

Lyon, France

Gustave Roussy

🇫🇷

Villejuif, France

Centre Oscar Lambret

🇫🇷

Lille, France

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Hopp Children's Cancer Center Heidelberg

🇩🇪

Heidelberg, Germany

CHU Timone Enfants

🇫🇷

Marseille, France

Charité University Medicine Berlin

🇩🇪

Berlin, Germany

Southampton General Hospital

🇬🇧

Southampton, United Kingdom

Great Ormond Street Hospital for Children

🇬🇧

London, United Kingdom

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