Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
50
Countries
1
Sites
3
high grade glioma
The primary objective of the study is to determine safety and tolerability of rapamycin in the treatment of high grade glioma in children
Key facts
- Sponsor
- Instytut Pomnik Centrum Zdrowia Dziecka
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 16 May 2023 → 27 Nov 2025
- Decision date (initial)
- 2025-01-11
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Medical Research Agency
External identifiers
- EU CT number
- 2024-515951-39-00
- EudraCT number
- 2021-006689-18
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Diagnosis, Efficacy, Safety
The primary objective of the study is to determine safety and tolerability of rapamycin in the treatment of high grade glioma in children
Secondary objectives 2
- The Secondary aim of the study is to asses safety and efficacy of rapamycin in a treatment of high grade glioma in children.
- The ecsplorative aim of the study is to collate genetic and epigenetic markers with the rapamycine efficacy and safety in pediatric high grade glioma patients.
Conditions and MedDRA coding
high grade glioma
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Age 3 to 18 years, inclusive.
- Informed consent signed by parents or legal guardian of minor and by patient over 13 years of age) for the study diagnostic and therapeutic procedures, including molecular -based diagnostic and prognostic tests using NGS method.
- Histological diagnosis of glioma WHO grade III and IV confirmed by reference pathologist.
- Negative result of the pregnancy test performed within 2 weeks prior to the start of the study in patients of reproductive age.
- Written consent to the use of effective contraception in sexually active patients.
Exclusion criteria 11
- Any severe comorbid disease (eg kidney insufficiency, immunological deficiencies, HIV infection).
- Clinically significant cardiovascular condition ( eg arrythmia)
- Previous (< 5 yrs ) diagnosis of malignant neoplasm.
- Active infection requiring systemic treatment.
- Known allergy to the studied products.
- Concomitant use of CYP3A or PgP inhibitors
- Radiological evidence of active intracranial hemorrhage (excluding receding post biopsy or focal bleeding).
- Major surgery in the past 28 days
- Diagnosis of DIPG
- Live vaccine intake <6 weeks prior to study inclusion
- Receipt of inactivated vaccine or mRNA vaccine <4 weeks prior to study inclusion.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary safety endpoint of rapamycin will be the assessment of the incidence of 3 and 4 grade adverse reactions (according to the CTCAE classification) during the treatment phase and follow-up.
Secondary endpoints 6
- OS (overall survival) after 15 months, 24 months, 3 years, 5 years
- EFS (event free survival) after 15 months, 24 months, 3 years, 5 years
- PFS (progression free survival) after 15 months, 24 months, 3 years, 5 years
- ORR ( overall response rate) according RAPNO (CR, PR, SD, PD) criteria
- Evaluation of adverse event seriousness according CTCAE
- Evaluation of the number of patients who experience adverse events that effects with premature termination of tratment during the therapeutic dose period. OS, EFS and PFS will be counted from the start of cancer treatment (the day of surgery).
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Rapamune 1 mg/mL oral solution
PRD505741 · Product
- Active substance
- Sirolimus
- Substance synonyms
- SEL-110.36, RAPAMYCIN, NPG-12G, (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone
- Pharmaceutical form
- ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 7320 mg milligram(s)
- Max treatment duration
- 183 Day(s)
- Authorisation status
- Authorised
- ATC code
- L04AH01 — -
- Marketing authorisation
- EU/1/01/171/001
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Instytut Pomnik Centrum Zdrowia Dziecka
- Sponsor organisation
- Instytut Pomnik Centrum Zdrowia Dziecka
- Address
- Aleja Dzieci Polskich 20
- City
- Warsaw
- Postcode
- 04-730
- Country
- Poland
Scientific contact point
- Organisation
- Instytut Pomnik Centrum Zdrowia Dziecka
- Contact name
- Marta Perek-Polnik
Public contact point
- Organisation
- Instytut Pomnik Centrum Zdrowia Dziecka
- Contact name
- Anna Drużdżel
Third parties 2
| Organisation | City, country | Duties |
|---|---|---|
| Transition Technologies- Science sp. z o.o. ORL-000011567
|
Warsaw, Poland | Code 10, Other, Data management |
| Instytut Pomnik Centrum Zdrowia Dziecka ORG-100012689
|
Warsaw, Poland | Other |
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Poland | Ended | 50 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Instytut Pomnik Centrum Zdrowia Dziecka
Department of Oncology, Aleja Dzieci Polskich 20, 04-730, Warsaw
Górnośląskie Centrum Zdrowia Dziecka
Department of Oncology, Hematology and Chemotherapy, Medyków 16, 40-758, Katowice
Uniwersytet Medyczny W Lodzi
Central Clinical Hospital of the University of Lodz- Department of Pedia, Al. Tadeusza Kosciuszki 4, 90-419, Lodz
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Poland | 2023-05-16 | 2023-09-11 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 14 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-515951-39-00_redacted | 2.1 |
| Recruitment arrangements (for publication) | Placeholder_BraimTOR-ONKO | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 13-15 yr_redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 16-17 yr_redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF biobanking_13-17 yr_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF biobanking_adults_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF biobanking_parents_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Data protection adults_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Data protection parents_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Information clause adults_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Information clause parents_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF parents_redacted | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Rapamune | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-16 | Poland | Acceptable with conditions 2025-01-08
|
2025-01-11 |