Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
400
Countries
16
Sites
57
Pediatric low-grade glioma harboring an activating RAF alteration requiring first-line systemic therapy
To compare the ORR assessed per RAPNO criteria by Independent Review Committee (IRC) of tovorafenib monotherapy versus standard of care (SoC) chemotherapy in patients with pediatric low-grade glioma harboring an activating RAF alteration requiring first-line systemic therapy.
Key facts
- Sponsor
- Day One Biopharmaceuticals Inc.
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 19 Apr 2023 → ongoing
- Decision date (initial)
- 2024-11-05
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Day One Biopharmaceuticals, Inc. (Day One)
External identifiers
- EU CT number
- 2024-510742-13-00
- EudraCT number
- 2022-001363-27
- ClinicalTrials.gov
- NCT05566795
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Pharmacokinetic, Others, Efficacy, Therapy
To compare the ORR assessed per RAPNO criteria by Independent Review Committee (IRC) of tovorafenib monotherapy versus standard of care (SoC) chemotherapy in patients with pediatric low-grade glioma harboring an activating RAF alteration requiring first-line systemic therapy.
Secondary objectives 3
- To compare the PFS assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RAPNO criteria.
- To compare the event-free survival (EFS) assessed by IRC of tovorafenib monotherapy versus SoC chemotherapy per RAPNO criteria.
- To compare the OS of tovorafenib monotherapy versus SoC chemotherapy.
Conditions and MedDRA coding
Pediatric low-grade glioma harboring an activating RAF alteration requiring first-line systemic therapy
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10065443 | Malignant glioma | 100000004864 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Treatment Phase with End of Treatment Visit Treatment Phase with tovorafenib (Arm 1) in 4 weeks cycles or SoC chemotherapy (Arm 2) in 4-6 weeks cycles. Clinical and radiological assessments as listed in the Protocol will be performed during the treatment phase. All patients randomized to Arm 1 will continue tovorafenib until any of the following occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study. All patients randomized to Arm 2 will receive chemotherapy until completion of therapy (ie, 60 weeks for COG-VC, 81 weeks for SIOPe-LGG-V/C, 70 weeks for VBL, or 72 weeks for monthly carboplatin), or until any of the folllowing occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study. The Treatment Phase ends with the End of (EOT) Visit after study treatment has ended.
|
Randomised Controlled | None | ||
| 2 | Long-Term Follow-Up Phase with 30 Day Safety Follow-Up Visit After completion of the Treatment Phase, patients will enter the Long-Term Follow-Up (LTFU) Phase, inclusive of the 30-Day Safety Follow-Up Visit. Assessments in this phase will occur according to the protocol, until the patient withdraws consent for further participation, is lost to follow-up, has died, or the study is closed. Patients who discontinue treatment due to a reason other than disease progression will continue radiographic response assessments per the protocol.
For patients in LTFU with evidence of disease progression (or those unable to continue radiographic response assessments), the site will contact the patient or the patient’s parent/legal guardian for follow-up assessments that may include subsequent anticancer therapies, survival status, and information about any secondary malignancies. Long-term follow-up may be conducted by telephone. For any patient who is lost-to-follow-up, the study site will attempt to ascertain survival information via public database search. If survival status still cannot be ascertained, patients will be considered lost to follow-up and will be censored appropriately. The first LTFU assessment will occur 3 months (± 1 month) after the EOT Visit.
A 30-Day Safety Follow-up Visit should occur approximately 30 days after the last dose of study treatment. Status of any unresolved adverse event (AE) should be assessed at the safety follow-up visit. Safety follow-up assessments may be performed as part of the EOT Visit if the latter was performed at least 28 days after final dose of the last cycle. Assessments and procedures for the safety follow-up visit will be conducted in accordance with the protocol.
|
Not Applicable | None |
Regulatory references
- Scientific advice from competent authorities
- Federal Institute For Drugs And Medical Devices, Spanish Agency Of Medicines And Medical Devices
- EMA paediatric investigation plan (PIP)
- EMEA-002763-PIP01-20
- Plan to share IPD
- No
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Less than 25 years of age with LGG with known activating RAF alteration
- Histopathologic diagnosis of glioma or glioneuronal tumor
- At least one measurable lesion
- Meet indication for first-line systemic therapy
Exclusion criteria 4
- Patient has any of the following tumor-histological findings: a. Schwannoma b. Subependymal giant cell astrocytoma (Tuberous Sclerosis) c. Diffuse intrinsic pontine glioma, even if histologically diagnosed as WHO Grade I-II
- Patient's tumor has additional pathogenic molecular alterations
- Known or suspected diagnosis of neurofibromatosis Type 1 or 2 (NF1/NF-2)
- Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/IV targeted therapy) including radiation.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- ORR, per RAPNO criteria, defined as the proportion of patients with overall confirmed response of complete response (CR), partial response (PR), or minor response (MR).
Secondary endpoints 3
- PFS per RAPNO criteria, defined as time from randomization to progressive disease (PD) or death from any cause, whichever comes first.
- EFS per RAPNO criteria, defined as time from randomization to PD, death from any cause, or initiation of any new anticancer therapy, whichever comes first.
- OS, defined as time from randomization up to death from any cause.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PRD11068230 · Product
- Active substance
- Tovorafenib
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 600.00 mg milligram(s)
- Max total dose
- 600.00 mg milligram(s)
- Max treatment duration
- 60 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- DAY ONE BIOPHARMACEUTICALS INC.
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/21/2434
PRD11068232 · Product
- Active substance
- Tovorafenib
- Pharmaceutical form
- POWDER FOR ORAL SUSPENSION
- Route of administration
- ORAL USE
- Max daily dose
- 600.00 mg milligram(s)
- Max total dose
- 600.00 mg milligram(s)
- Max treatment duration
- 60 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- DAY ONE BIOPHARMACEUTICALS INC.
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/21/2434
Comparator 7
VINCRISIN 1 mg/ml solution injectable, 2 mg
PRD4152768 · Product
- Active substance
- Vincristine Sulfate
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 2.00 mg milligram(s)
- Max total dose
- 83.00 mg milligram(s)
- Max treatment duration
- 81 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CA02 — VINCRISTINE
- Marketing authorisation
- BE143805
- MA holder
- TEVA PHARMA BELGIUM N.V./S.A
- MA country
- Belgium
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
cellcristin® 1 mg/ml Injektionslösung Wirkstoff: Vincristinsulfat
PRD1972960 · Product
- Active substance
- Vincristine Sulfate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 2.00 mg milligram(s)
- Max total dose
- 83.00 mg milligram(s)
- Max treatment duration
- 81 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CA02 — VINCRISTINE
- Marketing authorisation
- 3000427.00.00
- MA holder
- STADAPHARM GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Vincristinesulfaat Teva 1 mg/ml, oplossing voor injectie
PRD667758 · Product
- Active substance
- Vincristine Sulfate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 2.00 mg milligram(s)
- Max total dose
- 83.00 mg milligram(s)
- Max treatment duration
- 81 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CA02 — VINCRISTINE
- Marketing authorisation
- RVG 100081
- MA holder
- TEVA B.V
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Carboplatin Hikma 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung
PRD10240124 · Product
- Active substance
- Carboplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 1050.00 mg milligram(s)
- Max total dose
- 42000.00 mg milligram(s)
- Max treatment duration
- 81 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XA02 — CARBOPLATIN
- Marketing authorisation
- 3002152.00.00
- MA holder
- HIKMA FARMACÊUTICA (PORTUGAL), S.A.
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
VELBE 10 mg Trockensubstanz zur Injektionsbereitung
PRD1930421 · Product
- Active substance
- Vinblastine Sulfate
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 10.00 mg milligram(s)
- Max total dose
- 700.00 mg milligram(s)
- Max treatment duration
- 70 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CA01 — VINBLASTINE
- Marketing authorisation
- 12.269
- MA holder
- STADA ARZNEIMITTEL GMBH
- MA country
- Austria
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Vinblastinesulfaat 1 mg/ml PCH, oplossing voor injectie
PRD732197 · Product
- Active substance
- Vinblastine Sulfate
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 10.00 mg milligram(s)
- Max total dose
- 700.00 mg milligram(s)
- Max treatment duration
- 70 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CA01 — VINBLASTINE
- Marketing authorisation
- RVG 101349
- MA holder
- PHARMACHEMIE BV
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Vinblastin STADA 10 mg Pulver zur Herstellung einer Injektionslösung
PRD7810611 · Product
- Active substance
- Vinblastine Sulfate
- Substance synonyms
- VINBLASTINE SULPHATE
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 10.00 mg milligram(s)
- Max total dose
- 700.00 mg milligram(s)
- Max treatment duration
- 70 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01CA01 — VINBLASTINE
- Marketing authorisation
- 2201771.00.00
- MA holder
- STADAPHARM GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Day One Biopharmaceuticals Inc.
- Sponsor organisation
- Day One Biopharmaceuticals Inc.
- Address
- 2000 Sierra Point Parkway Suite 501
- City
- Brisbane
- Postcode
- 94005-1874
- Country
- United States
Scientific contact point
- Organisation
- Day One Biopharmaceuticals Inc.
- Contact name
- FIREFLY Clinical Trial Team
Public contact point
- Organisation
- Day One Biopharmaceuticals Inc.
- Contact name
- Day One Biopharmaceuticals, Inc. (Day One)
Third parties 26
| Organisation | City, country | Duties |
|---|---|---|
| ClinChoice ORL-000011076
|
Fort Washington, PA, United States | Code 10, Other |
| Myonex Limited ORG-100015937
|
Leicester, United Kingdom | Other |
| Azenta US Inc. ORG-100012907
|
Indianapolis, United States | Other |
| PPD Development LP ORG-100011560
|
Middleton, United States | Other |
| Shanghai Syntheall Pharmaceutical Co. Ltd. ORG-100012884
|
Shanghai, China | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | Other |
| Inseption Group LLC ORG-100041732
|
Lansdale, United States | Code 11, Other |
| Clinical Logistics Inc. ORG-100012712
|
Dartmouth, Canada | Other |
| Suvoda LLC ORG-100043523
|
Conshohocken, United States | Interactive response technologies (IRT) |
| Imaging Endpoints II LLC ORG-100045399
|
Scottsdale, United States | Other |
| Azenta Germany GmbH ORG-100022621
|
Griesheim, Germany | Other |
| Scout Clinical ORG-100042228
|
Dallas, United States | Other |
| Imperial Clinical Research Services International Limited ORG-100037442
|
Shepperton, United Kingdom | Other |
| Fisher Clinical Services GmbH ORG-100017323
|
Weil Am Rhein, Germany | Code 14, Other |
| Fisher Clinical Services Inc. ORG-100014726
|
Mount Prospect, United States | Code 14 |
| Experic LLC ORG-100051695
|
Cranbury, United States | Other |
| Q International Courier LLC ORG-100048842
|
Jamaica, United States | Other |
| Transperfect Translations International Inc. ORG-100043494
|
New York, United States | Other |
| Signant Health Global LLC ORG-100040604
|
Blue Bell, United States | Interactive response technologies (IRT) |
| Quotient Sciences Philadelphia LLC ORG-100018487
|
Boothwyn, United States | Other |
| QPS LLC ORG-100012847
|
Newark, United States | Other |
| Klifo A/S ORG-100016474
|
Glostrup, Denmark | Code 14, Other |
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | On site monitoring, Code 11, Code 12, Other, Code 2, Code 5, Data management, Code 8 |
| TecEx ORL-000014148
|
Luxembourg, Luxembourg | Other |
| Iqvia Inc. ORG-100010622
|
Durham, United States | Other |
| PRA Hellas CRO A.E. ORG-100048208
|
Nea Ionia, Greece | On site monitoring, Code 12, Code 2, Data management |
Locations
16 EU/EEA countries · 57 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ongoing, recruitment ended | 12 | 2 |
| Belgium | Ongoing, recruitment ended | 9 | 3 |
| Czechia | Ongoing, recruitment ended | 15 | 2 |
| Denmark | Ongoing, recruitment ended | 8 | 2 |
| Finland | Ongoing, recruitment ended | 9 | 2 |
| France | Ongoing, recruitment ended | 25 | 5 |
| Germany | Ongoing, recruitment ended | 35 | 14 |
| Greece | Ongoing, recruitment ended | 13 | 2 |
| Hungary | Ongoing, recruitment ended | 9 | 1 |
| Ireland | Ongoing, recruitment ended | 10 | 1 |
| Italy | Ongoing, recruitment ended | 20 | 9 |
| Netherlands | Ongoing, recruitment ended | 10 | 1 |
| Norway | Ongoing, recruitment ended | 12 | 2 |
| Slovenia | Ongoing, recruitment ended | 10 | 1 |
| Spain | Ongoing, recruitment ended | 35 | 7 |
| Sweden | Ongoing, recruitment ended | 13 | 3 |
| Rest of world
United States, New Zealand, Singapore, Canada, Jordan, Korea, Republic of, Australia, Switzerland, United Kingdom, Israel, Taiwan
|
— | 155 | — |
Investigational sites
Medical University Of Vienna
Universitätsklinik für Neurologie, Waehringer Guertel 18-20, Alsergrund, Vienna
Medizinische Universitaet Innsbruck
Department für Kinder- und Jugendheilkunde, Anichstrasse 35, 6020, Innsbruck
Universitair Ziekenhuis Gent
Pediatric Hemato-Oncology, Corneel Heymanslaan 10, 9000, Gent
Cliniques Universitaires Saint-Luc
Paediatric hemato-oncology, Hippokrateslaan 10, Batiment 54, Sint-Lambrechts-Woluwe
UZ Leuven
Pediatric Hematology and Oncology, Herestraat 49, 3000, Leuven
Fakultni Nemocnice Brno
Dětská Nemocnice, Klinika dětské onkologie, Cernopolni 9, Cerna Pole, Brno
Fakultni Nemocnice Motol A Homolka
Klinika dětské hematologie a onkologie, V Uvalu 84/1, Motol, Prague
Rigshospitalet
Department of Pediatric Hematology and Oncology Department of Pediatric and Adolescence Medicine, Blegdamsvej 9, 2100, Copenhagen Oe
Aarhus Universitetshospital
Department of Pediatrics and Adolescent Medicine, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N
Tampere University Hospital
Hematology and oncology, Elamanaukio 2, 33520, Tampere
HUS-Yhtymae
Hematology and oncology, Stenbackinkatu 9, 00290, Helsinki
Centre Oscar Lambret
Pediatric Unit. Oncology department, 3 Rue Frederic Combemale, 59000, Lille
Centre Hospitalier Regional De Marseille
La Timone Children Hospital, Department of Pediatric Hematology Oncology, 264 Rue Saint Pierre, 13005, Marseille
Institut Gustave Roussy
Pediatric Unit, 114 Rue Edouard Vaillant, 94800, Villejuif
Hospices Civils De Lyon
Institute of Pediatric Hematology and Oncology (iHOPe) GCS Lyon University Oncology, 1 Place Professeur Joseph Renaut, 69008, Lyon
Institut Curie
Pediatric department, 26 Rue D Ulm, 75005, Paris
University Medical Center Hamburg-Eppendorf
Paediatric Haematology and Oncology, Martinistrasse 52, Eppendorf, Hamburg
Universitaet Leipzig
Kinderklinik, selbst. Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie, Liebigstrasse 22, Zentrum-Suedost, Leipzig
Universitaetsklinikum Augsburg
Schwäbisches Kinderkrebszentrum, Stenglinstrasse 2, Kriegshaber, Augsburg
Evangelisches Klinikum Bethel gGmbH
Campus Bielefeld-Bethel, Universitätsklinik für Kinder- und Jugendmedizin, Grenzweg 14, Gadderbaum, Bielefeld
Universitaetsklinikum Tuebingen AöR
Universitäts klinik für Kinder- und Jugendmedizin, Hoppe-Seyler-Strasse 1, Nordstadt, Tuebingen
Universitaetsklinikum Essen AöR
Pediatrics III, Hufelandstrasse 55, Holsterhausen, Essen
Medizinische Hochschule Hannover
Department of Pediatric Hematology and Oncology, Carl-Neuberg-Strasse 1, Gross Buchholz, Hanover
Universitaetsklinikum Heidelberg AöR
Klinische Kooperationseinheit Pädiatrische Onkologie, Im Neuenheimer Feld 430, Neuenheim, Heidelberg
Universitaetsmedizin Goettingen
Division of Pediatric Oncology and Hematology, Robert-Koch-Strasse 40, Weende, Goettingen
Universitaetsklinikum Wuerzburg AöR
Kinderklinik und Poliklinik, Josef-Schneider-Strasse 2, Grombuehl, Wuerzburg
Universitaetsklinikum Erlangen AöR
Kinder und Jugendklinik, Loschgestrasse 15, Innenstadt, Erlangen
Medical Center - University Of Freiburg
Zentrum für Kinder-und Jugendmedizin, Mathildenstrasse 1, Stuehlinger, Freiburg Im Breisgau
Charite Universitaetsmedizin Berlin KöR
Pädiatrische Klinik mit Schwerpunkt Onkologie und Hämatologie, Augustenburger Platz 1, Wedding, Berlin
Universitaetsklinikum Frankfurt AöR
Clinic for Pediatrics and Adolescent Medicine, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
Nosokomeio Paidon I Agia Sofia
Unit of Pediatric Hematology and Oncology, First Department of Pediatrics., Thivon, Papadiamantopoulou, Athens
Athens General Children's Hospital Panagioti And Aglaia Kyriakou
Oncology Department, Thivon And Leivadias, Ampelokipoi, Athens
IRCCS Istituto Giannina Gaslini
Emato-Oncologia Pediatrica, Via Gerolamo Gaslini 5, 16147, Genoa
Azienda Ospedaliera di Padova
Oncoematologia Pediatrica, Via Nicolo' Giustiniani 2, 35128, Padova
Ospedale Pediatrico Bambino Gesu
Dipartimento di Oncoematologia, Terapia Cellulare, Terapie Geniche e trapianto Emopoietico, Piazza Di Sant'onofrio 4, 00165, Rome
Azienda Sanitaria Universitaria Friuli Centrale
P.O. Santa Maria della Misericordia SOC Clinica Pediatrica, Piazzale Santa Maria Della Misericordia 15, 33100, Udine
University Hospital Consorziale Policlinico
Unità Operativa Complessa di Pediatria ad Indirizzo Oncoematologico, Piazzale Giulio Cesare 11 Bari, 70124, Bari
Azienda Ospedaliera Universitaria Meyer IRCCS
SOSD NeuroOncology, Viale Gaetano Pieraccini 24, 50139, Florence
Azienda Ospedaliera Santobono Pausilipon
Dipartimento di Oncologia Pediatrica, Via Posillipo 226, 80123, Naples
Fondazione IRCCS Istituto Nazionale Dei Tumori
Dipartimento di Oncologia ed Ematologia, Via Giacomo Venezian 1, 20133, Milan
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
SC Oncoematologia Pediatrica, Piazza Polonia 94, 10126, Turin
Prinses Maxima Centrum voor Kinderoncologie B.V.
Pediatric hemato-Oncology, Heidelberglaan 25, 3584 CS, Utrecht
Oslo University Hospital HF
Oncology and Hematology, Sognsvannsveien 20, 0372, Oslo
Universitetssykehuset Nord-Norge HF
Oncology and Hematology, Sykehusvegen 38, 9019, Tromsoe
University Medical Center Ljubljana
Department of Hematology and Oncology, Bohoriceva Ulica 20, 1000, Ljubljana
Hospital Universitario La Paz
Pediatric Hemato-Oncology Department, Paseo De La Castellana 261, 28046, Madrid
Hospital Universitario De Cruces
Pediatric Hemato-Oncology Department, Cruces Plaza S/n, 48903, Barakaldo
University Hospital Virgen Del Rocio S.L.
Pediatric Oncology Department, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Sant Joan De Deu Barcelona
Pediatric Oncology Department, Passeig De Sant Joan De Deu 2, 08950, Esplugues De Llobregat
Hospital Universitari Vall D Hebron
Pediatric Oncology Department, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Hospital Universitario Y Politecnico La Fe
Pediatric Hemato-Oncology Department, Avenida De Fernando Abril Martorell 106, 46026, Valencia
Hospital Infantil Universitario Nino Jesus
Pediatric Hemato-Oncology Department, Avenida Menendez Pelayo 65, 28009, Madrid
Region Skane Skanes Universitetssjukhus
Pediatric Cancer center, Skånes Universitetssjukhus Lund, Lasarettsg. 48, 221 85 Lund, Entregatan 7, 222 42, Lund
Karolinska University Hospital
Childhood cancer center, Astrid Lindgrens Barnsjukhus, Eugeniav. 23, 171 76 Stockholm, Eugeniavagen 3, 171 64, Solna
Queen Silvia Childrens Hospital - Sahlgrenska University Hospital - Vaestra Goetalandsregionen
Pediatric Clinical Research Center, Drottning Silivias barnsjukhus, Behanglingsv. 7, 416 50 Göteborg, Behandlingsvagen 7, Harlanda, Gothenburg
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 |
|---|---|---|---|---|---|
| Austria | 2023-07-28 | 2024-07-24 | 2026-05-06 | ||
| Belgium | 2023-07-28 | 2024-08-10 | 2026-05-06 | ||
| Czechia | 2023-04-28 | 2023-06-28 | 2026-05-06 | ||
| Denmark | 2023-04-19 | 2023-05-24 | 2026-05-06 | ||
| Finland | 2023-08-29 | 2024-03-05 | 2026-05-06 | ||
| France | 2023-07-27 | 2023-08-09 | 2026-05-06 | ||
| Germany | 2023-06-06 | 2023-09-05 | 2026-05-06 | ||
| Greece | 2023-05-21 | 2023-06-02 | 2026-05-06 | ||
| Hungary | 2023-07-21 | 2024-07-05 | 2026-05-06 | ||
| Ireland | 2024-02-09 | 2024-09-04 | 2026-05-06 | ||
| Italy | 2023-09-28 | 2023-12-12 | 2026-05-06 | ||
| Netherlands | 2023-07-12 | 2024-04-10 | 2026-05-06 | ||
| Norway | 2023-11-10 | 2024-06-18 | 2026-05-06 | ||
| Slovenia | 2023-06-23 | 2024-03-21 | 2026-05-06 | ||
| Spain | 2023-05-04 | 2023-07-03 | 2026-05-06 | ||
| Sweden | 2023-05-22 | 2023-09-05 | 2026-05-06 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 2 · Art. 52 CTR
Serious breach SB-116929
- Sponsor became aware
- 2026-01-21
- Date of breach
- 2025-03-05
- Submission date
- 2026-01-30
- Member states concerned
- Hungary, Sweden, Netherlands, Norway, Italy, Czechia, Finland, France, Greece, Ireland, Spain, Denmark, Germany, Austria, Belgium, Slovenia
- Categories
- Regulation
- Areas impacted
- Regulatory
- Benefit-risk balance changed
- No
- Description
- Site 047-002 in Norway reported 11 SAEs with delays between the event onset dates and notification to the safety group, as the events occurred at an external hospital and the corresponding EMR/source documentation was reviewed only during the IMV following CRA request. The SAEs were reported within 24 hours of Investigator awareness, which occurred after EMR review initiated at the CRA’s request. As a result, this situation represents a potential impact to subject safety and regulatory compliance.
No individual impact to the subject rights and data integrity. As confirmed by the medical monitor, as the trial participant was managed according to the standard of care by the PI. The treating physicians managed this trial participant appropriately. The understanding of safety reporting as outlined in this CAPA was the root cause.
No impact on scientific rigor of the study as 1 trial participant is impacted out of 338, in the event that the affected data cannot be used, the overall scientific rigor of the study is not expected to be impacted.
This issue is considered a contributing factor to the classification of a Serious Breach due to the occurrence of 11 delayed SAE reports at the site. While no individual trial participant safety impact has been identified, the systemic and persistent nature of the delays represents a holistic risk that meets the Serious Breach threshold. - Sponsor actions
- Corrective/ Preventive Actions:
Correction:
1. Completed on 15-Jan-2026, ICON issued a notification to all sites reminding them of the requirement for timely SAE reporting for all trial participants, including those receiving standard of care therapy.
Corrective Action:
1. Planned by end of Feb-2026, Day One to conduct a review of Safety Database across the study to identify any similar or emerging trends related to delayed SAE reporting.
2. Planned by end of Feb-2026, ICON to conduct Training-Content Deficiency - Training deficiency for AE/SAE assessment and timely reporting after each trial participant visit will be addressed by Principal Investigator training the Sub Investigators for SAE reporting process of site and SAE reporting methods and timelines.
Preventative Action:
1. Timeline to be determined, Site to address lack of appropriate resources by adding a new staff member who can check EMR not just for site but also for local hospitals after each trial participant study visit if trial participant has reported AE/SAE.
| Organisation | City | Country | Type |
|---|---|---|---|
| Universitetssykehuset Nord-Norge HF | Tromsoe | Norway | Clinical investigator |
Serious breach SB-120621
- Sponsor became aware
- 2026-02-18
- Date of breach
- 2025-09-01
- Submission date
- 2026-02-25
- Member states concerned
- Hungary, Sweden, Netherlands, Norway, Italy, Czechia, Finland, France, Greece, Ireland, Spain, Denmark, Germany, Austria, Belgium, Slovenia
- Categories
- Protocol
- Areas impacted
- Subject safety, Data reliability or robustness, Other
- Benefit-risk balance changed
- Yes
- Description
- Temperature excursions for all investigational medicinal product (IMP) were not reported at Italian site 039-003, PI: Dr. Perillo for an extended period of time. Two patients may have received affected standard of care (SOC) chemotherapy investigational product (IMP) stored in inadequate conditions. The temperature excursions related to tovorafenib were excluded from any quality impact.
- Sponsor actions
- Site corrective action: Installed temperature monitoring device in ambient room, replaced data logger, and quarantined existing site SoC IP stock.
Sponsor corrective action: Designated all SoC IP stock at the site as “Not Fit For Use” in IRT, triggered replacement supply shipments with IRT auto shipments to better monitor temperature, and placed the site on a screening hold until CAPA resolution.
Preventative action: To be determined.
| Organisation | City | Country | Type |
|---|---|---|---|
| University Hospital Consorziale Policlinico | Bari | Italy | Clinical investigator |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 315 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol Clarification Letter PA2_1_2024-510742-13-00_redacted | 1 |
| Protocol (for publication) | D1_Protocol Clarification Letter PA2_2_2024-510742-13-00_redacted | 1 |
| Protocol (for publication) | D1_Protocol Clarification Letter PA3_1_2024-510742-13-00_redacted | 1 |
| Protocol (for publication) | D1_Protocol Clarification Letter PA3_2_2024-510742-13-00_redacted | 1 |
| Protocol (for publication) | D1_Protocol Clarification Letter PA3_3_2024-510742-13-00_redacted | 1 |
| Protocol (for publication) | D1_Protocol Clarification Letter PA3_4_2024-510742-13-00_redacted | 1 |
| Protocol (for publication) | D1_Protocol Clarification Letter PA3_5_2024-510742-13-00_redacted | 1 |
| Protocol (for publication) | D1_Protocol Clarification Letter_1_2024-510742-13-00_redacted | 2 |
| Protocol (for publication) | D1_Protocol Clarification Letter_2_2024-510742-13-00_redacted | 1 |
| Protocol (for publication) | D1_Protocol Clarification Letter_3_2024-510742-13-00_redacted | 1 |
| Protocol (for publication) | D1_Protocol_2024-510742-13-00_Greek_redacted | 3.2EU |
| Protocol (for publication) | D1_Protocol_2024-510742-13-00_redacted | 3.2EU |
| Recruitment arrangements (for publication) | K_AT_Recruitment Arrangements_Placeholder document | 1 |
| Recruitment arrangements (for publication) | K1_AT_Recruitment Procedure | 1.1 |
| Recruitment arrangements (for publication) | K1_BE_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K1_CZ_Recruitment Procedure_Bilingual | 1.0 |
| Recruitment arrangements (for publication) | K1_DE_Recruitment Procedure | 1.2 |
| Recruitment arrangements (for publication) | K1_EL_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K1_ES_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K1_FI_Recruitment Procedure_Finnish | 1.0 |
| Recruitment arrangements (for publication) | K1_FR_Recruitment Procedure_Bilingual | 1.0 |
| Recruitment arrangements (for publication) | K1_IE_Recruitment Procedure | 1 |
| Recruitment arrangements (for publication) | K1_IT_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K1_IT_Trial Card Unbranded_Italian_redacted | 1 |
| Recruitment arrangements (for publication) | K1_NL_Recruitment Procedure | 1.1 |
| Recruitment arrangements (for publication) | K1_NO_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K1_SE_Recruitment Procedure_Swedish | 1.0 |
| Recruitment arrangements (for publication) | K1_SI_Recruitment Procedure | 1.0 |
| Recruitment arrangements (for publication) | K2_AT_Recruitment Material_Trial Card_German_redacted | 1 |
| Recruitment arrangements (for publication) | K2_BE_Recruitment Material_Physician Referral Letter | 2.0 |
| Recruitment arrangements (for publication) | K2_BE_Recruitment Material_Trial Card Healthcare Professional | 1 |
| Recruitment arrangements (for publication) | K2_BE_Recruitment Material_Trial Card Patient Facing_Dutch_redacted | 1 |
| Recruitment arrangements (for publication) | K2_BE_Recruitment Material_Trial Card Patient Facing_French_redacted | 1 |
| Recruitment arrangements (for publication) | K2_CZ_Recruitment Material_Physician Referral Letter_Czech | 2.0 |
| Recruitment arrangements (for publication) | K2_CZ_Recruitment Material_Trial Card Healthcare Professional_Czech | 1 |
| Recruitment arrangements (for publication) | K2_CZ_Recruitment material_Trial Card Patient Facing_Czech_redacted | 1 |
| Recruitment arrangements (for publication) | K2_DE_Recruitment Material_Trial Card_German_redacted | 1 |
| Recruitment arrangements (for publication) | K2_DK_Recruitment Material_FF-2 PF Trial Card_Card_Bilingual_tc | 1 |
| Recruitment arrangements (for publication) | K2_DK_Recruitment Material_FF-2 PF Trial Card_Danish | 1 |
| Recruitment arrangements (for publication) | K2_DK_Recruitment Material_FF-2 PF Trial Card_Danish_redacted | 1 |
| Recruitment arrangements (for publication) | K2_EL_Recruitment material_Healthcare Professional Trial Card_Greek | 2 |
| Recruitment arrangements (for publication) | K2_EL_Recruitment material_Patient Facing Trial Card_Greek_redacted | 2 |
| Recruitment arrangements (for publication) | K2_EL_Recruitment material_Physician Referral Letter | 2.1 |
| Recruitment arrangements (for publication) | K2_ES_Recruitment Material_PF Trial Card_Spanish_redacted | 1 |
| Recruitment arrangements (for publication) | K2_FI_Recruitment Material_FF-2 PF Trial Card_Finnish_redacted | 1 |
| Recruitment arrangements (for publication) | K2_FR_Recruitment Material_Physician Referral Letter_French | 2.0 |
| Recruitment arrangements (for publication) | K2_FR_Recruitment Material_Trial Card HCP | 1 |
| Recruitment arrangements (for publication) | K2_FR_Recruitment Material_Trial Card Patient_French_redacted | 1 |
| Recruitment arrangements (for publication) | K2_HU_Recruitment Material_HCP Trial Card Unbranded | 1 |
| Recruitment arrangements (for publication) | K2_HU_Recruitment Material_Patient Facing Trial Card_Hungarian_redacted | 1 |
| Recruitment arrangements (for publication) | K2_HU_Recruitment Material_Physician Referral Letter_Hungarian | 2.0 |
| Recruitment arrangements (for publication) | K2_IE_Recruitment Material_HCP Trial Card | 1 |
| Recruitment arrangements (for publication) | K2_IE_Recruitment Material_Patient facing Trial Card_redacted | 1 |
| Recruitment arrangements (for publication) | K2_IE_Recruitment Material_Physician Referral Letter | 2.0 |
| Recruitment arrangements (for publication) | K2_IT_Recruitment Material_HCP Trial Card | 1 |
| Recruitment arrangements (for publication) | K2_IT_Recruitment Material_Physician Referral Letter | 2.0 |
| Recruitment arrangements (for publication) | K2_NL_Recruitment Material_Physician Referral Letter | 2.0 |
| Recruitment arrangements (for publication) | K2_NL_Recruitment Material_Trial Card Healthcare Professional | 1 |
| Recruitment arrangements (for publication) | K2_NL_Recruitment Material_Trial Card Patient Facing_Dutch_Redacted | 1 |
| Recruitment arrangements (for publication) | K2_NO_Recruitment Material_Trial Card_Norwegian_redacted | 1 |
| Recruitment arrangements (for publication) | K2_SE_Recruitment Material_FF-2 PF Trial Card_Swedish_redacted | 1 |
| Recruitment arrangements (for publication) | K2_SI_Recruitment Material_Trial Card_Slovenian_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_AT_SIS-ICF_Addendum Parental Optional Tumor Specimen_German_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_AT_SIS-ICF_Addendum Participant Optional Tumor Specimen_German_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_AT_SIS-ICF_Assent 14 years and older_German | 5.0 |
| Subject information and informed consent form (for publication) | L1_AT_SIS-ICF_Assent 7-13 years_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_AT_SIS-ICF_Main Parents_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_AT_SIS-ICF_Main Participants_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_AT_SIS-ICF_Pregnant Partner_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_AT_SIS-ICF_Scout_German_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_AT_SIS-ICF_site info_Bilingual_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Assent 13 Years Old and Older_Dutch_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Assent 13 Years Old and Older_French_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Assent 7-12 Years Old_Dutch_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Assent 7-12 Years Old_French_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Parental Main_Dutch_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Parental Main_French_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Participant Main_Dutch_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Participant Main_French_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Pregnant Partner ICF_Dutch_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_BE_SIS-ICF_Pregnant Partner ICF_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Assent 12-14 Years Old_Czech | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Assent 12-14 Years Old_Czech_hl | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Assent 15-17 Years Old_Czech | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Assent 15-17 Years Old_Czech_hl | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Main Parental_Czech_hl_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Main Parental_Czech_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Main Participant_Czech_hl_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Main Participant_Czech_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Parental Continuing Study Drug After Progression_Czech | 2.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Parental Optional Consent to Receive Tovorafenib_Czech | 1.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Parental Optional Future Research_Czech_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Parental Optional Tumor Specimen_Czech_hl_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Parental Optional Tumour Specimen_Czech_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Parental Privacy_Czech_hl_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Parental Privacy_Czech_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Participant Continuing Study Drug After Progression_Czech | 2.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Participant Optional Consent to Receive Tovorafenib_Czech | 1.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Participant Optional Future Research_Czech_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Participant Optional Tumor Specimen_Czech_hl_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Participant Optional Tumour Specimen_Czech_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Participant Privacy_Czech_hl_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Participant Privacy_Czech_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Pregnant Partner_Czech_hl_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_CZ_SIS-ICF_Pregnant Partner_Czech_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Add Opt Biopsy_Adults_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Add Opt Biopsy_Parents_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Add Opt Use Leftover Samples_Adults_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Add Opt Use Leftover Samples_Parents_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Assent 12-16 Yrs_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Assent 7-11 Yrs_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Main_Adults_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Main_Parents_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Pregnancy_German_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Scout_German_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_DE_SIS-ICF_Sub-Study_Placeholder Document | 1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Addendum Right to Not Know_Danish | 5.0 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Addendum_Assent 15-17 years Future Research_Danish_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Addendum_Assent 15-17 years Optional Tumor_Danish_Redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Addendum_Continuation_Danish | 5.0 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Addendum_Parental Optional Tumor_Danish_Redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Addendum_Participant Optional Tumor_Danish_Redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Addendum_Participant Optional Tumor_Danish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Addendum_Participant Parents Future Research ICF_Danish_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Assent 11 years and younger_Danish_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Assent 12-14 years_Danish | 5.1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Assent 15-17 years_Danish_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Assent 15-17 years_Danish_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Parental Main_Danish_Redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Participant Main_Danish_Redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Power of Attorney Between Parents_Danish | 1.0 |
| Subject information and informed consent form (for publication) | L1_DK_SIS-ICF_Pregnancy Data Collection_Danish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Assent 13-15 Years old_Greek | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Assent 16-18 Years old_Greek | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Assent Optional Tumor_Greek | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Assent_7-12 Years old_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Assent_Pregnant Partner_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Parent of Pregnant Partner_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Parental Main_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Parental Optional Tumor_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Participant Adolescent to Adult_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Participant Main_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Participant Optional Tumor_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Pregnant Partner Adolescent to adult_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Pregnant Partner_Greek_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_EL_SIS-ICF_Scout_Greek_redacted | 2.1 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Assent 12-17_Spanish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Parental Main_Spanish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Parental Optional Tumor_Spanish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Participant Main_Spanish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Participant Optional Tumor_Spanish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Pregnant Partner_Spanish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Scout_Spanish_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_ES_SIS-ICF_Sub-Study_Placeholder document | 3 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Addendum_Adult Optional Tumor_Finnish_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Addendum_Participant 15-17 years_Optional Tumor_Finnish_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Adult-Parent Cross-Over_Finnish_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Adult-Parent Post-tumor treatment_Finnish_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Assent 12-14 years_Finnish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Assent 15-17 Cross-Over Treatment_Finnish_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Assent 15-17 Post-Tumor Treatment_Finnish_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Assent under 12 years_Finnish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Assent_Participant 15-17 years_Main_Finnish_redacted | 5.2 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Consent 15-17 years_Cross-Over Treatment_Finnish_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Consent 15-17 years_Post-Tumor Progression_Finnish_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Consent_Participant 15-17 years_Main_Finnish_redacted | 5.2 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Notification to guardians of 15-17 year olds_Main trial_Finnish | 5.1 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Notification to guardians of 15-17 year olds_Optional Future Research_Finnish | 5.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Parental Main_Finnish_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Parental Notification_Cross-Over treatment_Finnish | 1.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Parental Notification_Post-Tumor Progression_Finnish | 1.0 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Participant Main_Finnish_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Pregnancy_Finnish_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_FI_SIS-ICF_Scout_Finnish_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Addendum_Participant Optional Tumor_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Assent 6 years and under_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Assent 7-12 Years Old_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Assent_13 Years and Older_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Assent_Addendum_French | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Cross-over_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Minor becoming major_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Parental Main_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Parental Optional Tumor_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Participant Main_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Pregnant Partner_French_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Scout_French_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_FR_SIS-ICF_Sub-study_Placeholder document | 1 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Main 12-17 years_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Main 5 or less years_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Main 6-11 years_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Main Adult_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Main Parent_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Optional tumor specimen 12-17 years_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Optional tumor specimen 5 or less years_Hungarian | 2.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Optional tumor specimen 6-11 years_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Optional Tumor Specimen Adult_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Optional Tumor Specimen Parent_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Pregnant Partner_Hungarian | 3.0 |
| Subject information and informed consent form (for publication) | L1_HU_ICF_Scout_Hungarian_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Main 12-17 years_Hungarian | 5.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Main 5 years or less_Hungarian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Main 6-11 years_Hungarian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Main Adult_Hungarian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Main Parent_Hungarian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Optional tumor specimen 12-17 years_Hungarian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Optional tumor specimen 5 years or less_Hungarian_redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Optional tumor specimen 6-11 years_Hungarian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Optional tumor specimen Adult_Hungarian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Optional tumor specimen Parent_Hungarian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_HU_SIS-ICF_Pregnant Partner_Hungarian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IE_SIS-ICF_Adult 16 plus Treatment Beyond Progression | 1.0 |
| Subject information and informed consent form (for publication) | L1_IE_SIS-ICF_Assent 13-15_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IE_SIS-ICF_Assent 7-12_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IE_SIS-ICF_Main_Adults 16 plus_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_IE_SIS-ICF_Main_Parents_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_IE_SIS-ICF_Parents Treatment Beyond Progression | 1.0 |
| Subject information and informed consent form (for publication) | L1_IE_SIS-ICF_Pregnant Partner_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IE_SIS-ICF_Scout Clinical_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Adult_Italian_redacted | 3.1 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Adult_Optional_Italian_redacted | 3.1 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Assent 13 Years Old and Older_Ukrainian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Assent 7-12 Years Old_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Assent_13 Years Old and Older_Italian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Assent_13 Years Old and Older_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Assent_7-12 Years Old_Italian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_EC Approval_Italian_redacted | 1 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Parental_Italian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Parental_Optional_Italian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Parental_Optional_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Parental_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Parental_Ukrainian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Participant Main_Italian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Participant Main_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Participant Optional_Italian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Participant Optional_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Pregnancy_Italian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Pregnancy_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Scout_Italian_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Scout_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Scout_Ukrainian_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L1_IT_SIS-ICF_Sub-study_Placeholder document | 1 |
| Subject information and informed consent form (for publication) | L1_NL_SIS-ICF_Assent ICF 12-16 years old_Dutch_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_NL_SIS-ICF_Parent Main_Dutch_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_NL_SIS-ICF_Participant Main_Dutch_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_NL_SIS-ICF_Pregnant Partner_Dutch_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Addendum_Continuation_Norwegian | 5.0 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Addendum_Parental Optional biobank_Norwegian_redacted | 3.1 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Addendum_Parental Optional Tumor_Norwegian_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Addendum_Participant Optional biobank_Norwegian_redacted | 3.1 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Addendum_Participant Optional Tumor_Norwegian_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Assent 11 years and younger_Norwegian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Assent 12-15 years_Norwegian | 5.0 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Assent 16-17 yr_Norwegian | 5.1 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Parental Main_Norwegian_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Participant Main_Norwegian_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Pregnancy Data Collection_Norwegian_redacted | 5.1 |
| Subject information and informed consent form (for publication) | L1_NO_SIS-ICF_Scout_Norwegian_redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Addendum_Parental Optional Tumor_Swedish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Addendum_Participant Optional Tumor_Swedish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Assent 11 yr and under_Swedish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Assent 12-14 yr_Swedish | 5.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Assent 15-17 yr_Swedish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Parental Main_Swedish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Participant Main_Swedish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Pregnancy Data Collection_Swedish_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SE_SIS-ICF_Scout_Swedish_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L1_SI_SIS-ICF_Assent 13_Slovenian | 5.0 |
| Subject information and informed consent form (for publication) | L1_SI_SIS-ICF_Assent 7-12_Slovenian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SI_SIS-ICF_Parental Main_Placeholder | 2 |
| Subject information and informed consent form (for publication) | L1_SI_SIS-ICF_Parental Main_Slovenian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SI_SIS-ICF_Parental Optional_Slovenian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SI_SIS-ICF_Participant Main_Slovenian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SI_SIS-ICF_Participant Optional_Slovenian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SI_SIS-ICF_Pregnant Participant_Slovenian_redacted | 4.0 |
| Subject information and informed consent form (for publication) | L1_SI_SIS-ICF_Pregnant Partner_Slovenian_redacted | 5.0 |
| Subject information and informed consent form (for publication) | L1_SI-SIS-ICF_Scout_Slovenian_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L2_BE_Other Subject Material_Scout Agreement_Dutch_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L2_BE_Other Subject Material_Scout Agreement_French_redacted | 2.0 |
| Subject information and informed consent form (for publication) | L2_CZ_Other Subject Material_Dosing Diary Liquid_Czech | 6.0 |
| Subject information and informed consent form (for publication) | L2_CZ_Other Subject Material_Dosing Diary Tablet_Czech | 5.0 |
| Subject information and informed consent form (for publication) | L2_CZ_Other Subject Material_FU tricolumn_Czech | 5.0 |
| Subject information and informed consent form (for publication) | L2_CZ_Other Subject Material_FU_Czech | 5.0 |
| Subject information and informed consent form (for publication) | L2_CZ_Other Subject Material_Patient Wallet Card_Czech | 1.0 |
| Subject information and informed consent form (for publication) | L2_EL_Other Subject Material_Placeholder document | 2 |
| Subject information and informed consent form (for publication) | L2_HU_Other subject material_Patient Emergency Card_Hungarian | 3.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Carboplatin Hikma | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Carboplatin Hikma_2 | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Cellcristin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Velbe | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Vinblastine Stada | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Vinblastine Sulfate Teva NL | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Vincrisin Teva BE | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Vincrisin Teva BE_Dutch | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Vincristine Sulfate Teva NL | 2 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_Czech_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_Dutch_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_French_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_German_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_Greek_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_Hungarian_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_Italian_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_Norwegian_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_Slovenian_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_Spanish_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-510742-13-00_Swedish_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-510742-13-00_Czech_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-510742-13-00_French_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-510742-13-00_German_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-510742-13-00_Greek_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-510742-13-00_Hungarian_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-510742-13-00_Italian_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-510742-13-00_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-510742-13-00_Slovenian_redacted | 3.2EU |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-510742-13-00_Spanish_redacted | 3.2EU |
Application history
8 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-25 | Netherlands | Acceptable 2024-10-29
|
2024-10-29 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-02-05 | Netherlands | Acceptable | 2025-03-13 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-04-14 | Netherlands | Acceptable 2025-07-25
|
2025-07-25 |
| 4 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-08-12 | Acceptable | 2025-09-10 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-08-12 | Acceptable | 2025-09-03 | |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-08-14 | Acceptable | 2025-09-17 | |
| 7 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-11-06 | Acceptable | 2025-11-19 | |
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-03-23 | Acceptable | 2026-03-23 |