Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
18
Countries
1
Sites
1
Metastatic medulloblastoma and other embryonal tumours
To evaluate safety of first line standard and high-dose chemotherapy associated with craniospinal irradiation in pediatric and young adult patients with high risk medulloblastoma and other embryonal tumours
Key facts
- Sponsor
- Azienda Ospedaliera Universitaria Meyer IRCCS
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 27 Jan 2025 → ongoing
- Decision date (initial)
- 2025-01-27
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-518964-11-01
- EudraCT number
- 2017-000801-19
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Therapy, Efficacy
To evaluate safety of first line standard and high-dose chemotherapy associated with craniospinal irradiation in pediatric and young adult patients with high risk medulloblastoma and other embryonal tumours
Secondary objectives 2
- To evaluate the effectiveness of treatment in terms of progression-free survival, overall survival and responses to therapy.
- To evaluate neuropsychological and psychological aspects, endocrinological and visual sequelae.
Conditions and MedDRA coding
Metastatic medulloblastoma and other embryonal tumours
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10027107 | Medulloblastoma | 100000004864 |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2024-518964-11-00 | An interventional, open-label, Phase II study, to evaluate safety and efficacy of standard and high-dose chemotherapy associated with craniospinal irradiation in patients with metastatic medulloblastoma and other embryonal tumours | Azienda Ospedaliera Universitaria Meyer IRCCS |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 11
- First diagnosed, previously untreated, patients with high-risk medulloblastoma (according to WHO 2016 classification): metastatic; anaplastic or large cell; partially resected (residual volume on two floors> 1.5cm2) according to WHO classification (2016); N-MYC C-MYC amplified
- Patients with other embryonic tumors (WHO classification 2016) - embryonic tumor with C19MC-altered multilayer rosettes; embryonic tumor with multilayer rosettes not otherwise specified, medulloepithelioma, CNS neuroblastoma, CNS ganglioneuroblastoma, CNS embryonic tumor not otherwise specified, CNS embryonic tumor with rhabdoid features - of first diagnosis, previously untreated (with chemo and radiotherapy) and treated only surgically
- First diagnosed Pinealoblastomas (WHO 2016), previously untreated (with chemo and radiotherapy) and treated only surgically
- Males and females aged >3 years and <21 years at time of the diagnosis
- Life expectancy > or = 12 months
- Karnofsky/Lansky > or = 40 %
- Adequate hematological function (leucocyte > or = 2.0 x 10^9/l - Hemoglobin > or = 10 g/dl - platelet > or = 50 x 10^9/l)
- Adequate liver function (total bilirubin < or = 2.5 x ULN - ALT/AST < or = 5.0 x ULN)
- Adequate renal function (serum creatinine < or = 1.5 x ULN)
- Written informed consent obtained from the patient/parents or legal representative
- Availability for treatment and ability to be compliant with the protocol
Exclusion criteria 10
- Any disease or condition that contraindicates the use of the study treatment (es. serious mental retardation, brain palsy, congenital syndrome, cardiomyopathy, psychosocial problems)
- Administration of a first-line chemotherapy cycle at the same time as the start of the study
- Concomitant partecipation to other clinical trial
- Pregnancy or breastfeeding
- Inadequate contraception by patients of both sexes
- Hypersensibility to active principles or excipients
- Severe bone-marrow depression
- Concomitant administration of live attenuated vaccines
- Inability to comply for study follow-up
- Other contraindications reported in the SmPC
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Percentage of subjects with neurological symptoms >=G3, evaluated according to CTCAE 4.0, not present at the beginning of postoperative chemoradiotherapy and not related to the recurrence / progression of the disease - Percentage of subjects with SAE - Percentage of subjects with SAE leading to withdrawal from the study - Mortality due to adverse events
Secondary endpoints 5
- Progression free survival (PFS) defined as time frame between the date of the enrolment and the date tumour progression or death
- Overall survival (OS) defined as time frame between the date of the enrolment and the death to any cause
- Difference in scoring for neuropsychological (Griffiths-III, WPPSI-III, WISC-IV, WAIS-IV, Rey, Nepsy-2) and psycological (PedsQL, CBCL) scales
- Rate of treatment response: CR, complete response the complete disappearance of all radiographic and/or cytological evidence of tumor; PR, partial response >= 50% reduction in the product of the perpendicular diameters of the tumor with negative cytology - SD, stable disease <= 25%reduction in tumor size; PD, progressive disease >= 25% increase in tumor size or the appearance of tumor in previously uninvolved areas
- Frequency of endocrinological and visual sequelae
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 7
SUB07337MIG · Substance
- Active substance
- Etoposide
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 2.4 gm/m2 gram(s)/square meter
- Max total dose
- 2.4 gm/m2 gram(s)/square meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08856MIG · Substance
- Active substance
- Methotrexate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 8 gm/m2 gram(s)/square meter
- Max total dose
- 8 gm/m2 gram(s)/square meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08567MIG · Substance
- Active substance
- Lomustine
- Pharmaceutical form
- CAPSULE
- Route of administration
- ORAL
- Max daily dose
- 80 mg/m2 milligram(s)/square meter
- Max total dose
- 693 mg/m2 milligram(s)/square meter
- Max treatment duration
- 9 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10985MIG · Substance
- Active substance
- Thiotepa
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 300 mg/m2 milligram(s)/square meter
- Max total dose
- 900 mg/m2 milligram(s)/square meter
- Max treatment duration
- 3 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00069MIG · Substance
- Active substance
- Vinorelbine
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 20 mg/m2 milligram(s)/square meter
- Max total dose
- 640 mg/m2 milligram(s)/square meter
- Max treatment duration
- 32 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06859MIG · Substance
- Active substance
- Cyclophosphamide
- Pharmaceutical form
- INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 4 gm/m2 gram(s)/square meter
- Max total dose
- 4 gm/m2 gram(s)/square meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06614MIG · Substance
- Active substance
- Carboplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 800 mg/m2 milligram(s)/square meter
- Max total dose
- 800 mg/m2 milligram(s)/square meter
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Azienda Ospedaliera Universitaria Meyer IRCCS
- Sponsor organisation
- Azienda Ospedaliera Universitaria Meyer IRCCS
- Address
- Viale Gaetano Pieraccini 24
- City
- Florence
- Postcode
- 50139
- Country
- Italy
Scientific contact point
- Organisation
- Azienda Ospedaliera Universitaria Meyer IRCCS
- Contact name
- Clinical Trial Office
Public contact point
- Organisation
- Azienda Ospedaliera Universitaria Meyer IRCCS
- Contact name
- Clinical Trial Office
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Ongoing, recruitment ended | 18 | 1 |
| 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 |
|---|---|---|---|---|---|
| Italy | 2025-01-27 | 2025-01-27 | 2025-05-23 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 17 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol v5 2024-518964-11_FP | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 14_17yr v3 01 02 2021 FP | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF 7_13yr v3 01 02 2021 FP | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults v3 01 02 2021 FP | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF parents v3 01 02 2021 FP | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF privacy adults v2 01 02 2021 FP | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF privacy parents v2 01 02 2021 FP | 1 |
| Subject information and informed consent form (for publication) | L2_Information for GP v2 01 02 2021 FP | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Carboplatin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Cyclophosphamide | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Etoposide | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Lomustine | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Methotrexate | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Thiotepa | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Vinorelbine | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis ITA v5 2024-518964-11 FP | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-11-22 | Italy | Acceptable 2024-12-20
|
2025-01-27 |