Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
100
Countries
1
Sites
2
diffuse intrinsic pontine glioma
The aim of the study is to develop the optimal treatment for patients with DIPG by identifying molecular markers important for therapy, adjusting the type of medicinal product to the indicated markers and assessing the safety and efficacy of selected drugs (sirolimus, trametinib) in the treatment of DIPG in children
Key facts
- Sponsor
- Instytut Pomnik Centrum Zdrowia Dziecka
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 18 Dec 2024 → ongoing
- Decision date (initial)
- 2024-12-18
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Medical Research Agency
External identifiers
- EU CT number
- 2024-515952-19-00
- EudraCT number
- 2021-001375-16
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Diagnosis, Safety
The aim of the study is to develop the optimal treatment for patients with DIPG by identifying molecular markers important for therapy, adjusting the type of medicinal product to the indicated markers and assessing the safety and efficacy of selected drugs (sirolimus, trametinib) in the treatment of DIPG in children
Secondary objectives 6
- assessment of the efficacy and safety of selected drugs (sirolimus, trametinib) in the treatment of diffuse infiltrating ponsal gliomas in children
- to evaluate the safety and efficacy of the simultaneous irradiation and use of sirolimus
- adjusting the type of medicinal product to the indicated markers
- identification of molecular markers important for therapy
- creating a repository of genetic and clinical data of patients with DIPG
- development of the molecular profile of DIPG tumors
Conditions and MedDRA coding
diffuse intrinsic pontine glioma
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- 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
- Diagnosis of diffuse intrinsic pontine glioma (DIPG) based on clinical and radiological criteria
- Histological diagnosis of glioma WHO grade III and IV confirmed by reference pathologist
Exclusion criteria 8
- 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Overall survival (OS) from the time of diagnosis until last visit or death
- Safety assessment of sirolimus administered during radiotherapy and in combination with trametinib as adjunctive treatment after irradiation
Secondary endpoints 4
- Progression free survival from diagnosis to progression
- Response rate assessed at time points specified in the protocol (MRI every 2 months from commnecement of systemic treatment)
- Quality of life assessment (using PedQoL- pediatric quality of life inventory) at time points specified in the protocol
- Comparison of safety in 2 groups of patients; treated with sirolimus alone or in combination with trametinib
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
Rapamune 1 mg/mL oral solution
PRD3342092 · 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 USE
- Max daily dose
- 3 mg/m2 milligram(s)/sq. meter
- Max total dose
- 1092 mg/m2 milligram(s)/square meter
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AH01 — -
- Marketing authorisation
- EU/1/01/171/001
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD3342088 · 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
- COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 3 mg/m2 milligram(s)/square meter
- Max total dose
- 1092 mg/m2 milligram(s)/square meter
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- L04AH01 — -
- Marketing authorisation
- EU/1/01/171/007
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Mekinist 0.5 mg film-coated tablets
PRD3045762 · Product
- Active substance
- Trametinib
- Substance synonyms
- GSK1120212B
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 1 mg/m2 milligram(s)/sq. meter
- Max total dose
- 322 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 46 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EE01 — -
- Marketing authorisation
- EU/1/14/931/001
- MA holder
- NOVARTIS EUROPHARM LIMITED
- 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
- Bożenna Dembowska-Bagińska
Public contact point
- Organisation
- Instytut Pomnik Centrum Zdrowia Dziecka
- Contact name
- Monika Drogosiewicz
Third parties 3
| Organisation | City, country | Duties |
|---|---|---|
| Warszawski Uniwersytet Medyczny ORL-000010050
|
Warszawa, Poland | Laboratory analysis |
| Neuca S.A. ORG-100019408
|
Torun, Poland | Other |
| Cefea Sp. z o.o. S.K. ORG-100015378
|
Warsaw, Poland | Other |
Locations
1 EU/EEA country · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Poland | Ongoing, recruiting | 100 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
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 | 2024-12-18 | 2024-12-20 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protokol_2024-515952-19-00_for publication_redacted | 4 |
| Recruitment arrangements (for publication) | PLACEHOLDER DIPGen | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Assent over 13 yr_for publication_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Data Protection | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Parents_for publication_redacted | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Mekinist | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-16 | Poland | Acceptable 2024-12-13
|
2024-12-18 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-04-25 | Poland | Acceptable 2024-12-13
|
2025-04-25 |