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

Tracking Information

• First Submitted Date: October 20, 2020
• First Posted Date: October 30, 2020
• Last Update Posted Date: May 11, 2022
• Actual Study Start Date: March 16, 2021
• Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 29, 2020)

• 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)
• 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)
• 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)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 29, 2020)

• 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.
• 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
• 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)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1

Study Design

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

• Condition: Pediatric Cancer

Intervention

Drug: Temozolomide Oral Suspension

One prescribed oral dose (range 75 to 200 mg/m2) once daily for 5 days

Other Name: KIMOZO, Ped-TMZ

Study Arms

Experimental: Single arm

Temozolomide 40 mg/ml, Oral suspension

Intervention: Drug: Temozolomide Oral Suspension

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 29, 2020): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2022
• Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

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

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

• Listed Location Countries: France, Germany, Netherlands, Spain, United Kingdom

Administrative Information

• NCT Number: NCT04610736
• Other Study ID Numbers: ORP-TMZ-I- b
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Orphelia Pharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Orphelia Pharma
• Original Study Sponsor: Same as current
• Collaborators: ClinSearch

Investigators

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

• PRS Account: Orphelia Pharma
• Verification Date: May 2022