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

• ClinicalTrials.gov Identifier: NCT04610736
• Recruitment Status: Recruiting
• First Posted: October 30, 2020
• Last Update Posted: May 11, 2022
• Sponsor: Orphelia Pharma
• Collaborator: ClinSearch
• Information provided by (Responsible Party): Orphelia Pharma

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pediatric Cancer	Drug: Temozolomide Oral Suspension	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Non-randomized, international, multi-centre, open-label, single arm study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TEMOkids Study: A Population Pharmacokinetic, Acceptability and Safety Study for KIMOZO, a Paediatric Oral Suspension of Temozolomide
• Actual Study Start Date: March 16, 2021
• Estimated Primary Completion Date: August 2022
• Estimated Study Completion Date: August 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single arm; Temozolomide 40 mg/ml, Oral suspension	Drug: Temozolomide Oral Suspension; One prescribed oral dose (range 75 to 200 mg/m2) once daily for 5 days; Other Name: KIMOZO, Ped-TMZ

Outcome Measures

Primary Outcome Measures :

1. Population Phamacokinetic parameter: AUC24 [ Time Frame: 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 ]
   Estimated by a population analysis performed with NONMEM (7.4)
2. Population Phamacokinetic parameter: Cmax [ Time Frame: 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 ]
   Estimated by a population analysis performed with NONMEM (7.4)
3. Population Phamacokinetic parameter: T1/2 [ Time Frame: 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 ]
   Estimated by a population analysis performed with NONMEM (7.4)

Secondary Outcome Measures :

1. Acceptability of the oral suspension of temozolomide: score [ Time Frame: At 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.
2. Incidence of treatment-emergent adverse events [ Time Frame: Through 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
3. Activity of the oral suspension of temozolomide [ Time Frame: At 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)

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Caroline Lemarchand, PharmD; +33142770818; caroline.lemarchand@orphelia-pharma.eu

Contact: Hugues Bienaymé, PhD; +33142770818; hugues.bienayme@orphelia-pharma.eu

Locations

France

Centre Oscar Lambret; Recruiting

Lille, France, 59000

Contact: Anne-Sophie Defachelles, MD

Institut d'Hématologie et d'Oncologie Pédiatrique; Recruiting

Lyon, France, 69008

Contact: Pierre Leblond, MD

CHU Timone Enfants; Recruiting

Marseille, France, 13005

Contact: Nicolas André, MD

Institut Curie; Recruiting

Paris, France, 75005

Contact: Isabelle Aerts, MD

Gustave Roussy; Recruiting

Villejuif, France, 94800

Contact: Samuel Abbou, MD

Germany

Charité University Medicine Berlin; Not yet recruiting

Berlin, Germany, 13353

Contact: Anne Thorwarth, MD

Hopp Children's Cancer Center Heidelberg; Not yet recruiting

Heidelberg, Germany, 69120

Contact: Olaf Witt, MD

Netherlands

Princess Maxima Center for Pediatric Oncology; Recruiting

Utrecht, Netherlands, 3584 CS

Contact: Natasha Van Eijkelenburg, MD

Spain

Hospital Universitari Vall d'Hebron; Not yet recruiting

Barcelona, Spain, 08035

Contact: Lucas Moreno, MD

United Kingdom

Southampton General Hospital; Recruiting

Southampton, United Kingdom, SO16 6YD

Contact: Juliet Gray, MD

Sponsors and Collaborators

Orphelia Pharma

ClinSearch

Investigators

• Principal Investigator: Samuel Abbou, MD; Gustave Roussy, Cancer Campus, Grand Paris

More Information

• Responsible Party: Orphelia Pharma
• ClinicalTrials.gov Identifier: NCT04610736
• Other Study ID Numbers: ORP-TMZ-I- b
• First Posted: October 30, 2020
• Last Update Posted: May 11, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Orphelia Pharma:

neuroblastoma; other pediatric cancers requiring temozolomide

Additional relevant MeSH terms:

Temozolomide; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents