Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
110
Countries
7
Sites
21
Multiple indications
The primary objective is to evaluate long-term safety as assessed by occurrence of AEs/SAEs.
Key facts
- Sponsor
- Novartis Pharma AG
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 15 Jan 2018 → ongoing
- Decision date (initial)
- 2024-08-12
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- ORG-100003908
External identifiers
- EU CT number
- 2023-509318-13-00
- EudraCT number
- 2017-001987-39
- ClinicalTrials.gov
- NCT03340506
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Others, Safety
The primary objective is to evaluate long-term safety as assessed by occurrence of AEs/SAEs.
Secondary objectives 1
- To evaluate clinical benefit as assessed by the Investigator.
Conditions and MedDRA coding
Multiple indications
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 27.0 | LLT | 10027481 | Metastatic melanoma | 10029104 |
| 20.0 | SOC | 10029104 | Neoplasms benign malignant and unspecified (incl cysts and polyps) | 2 |
| 21.1 | PT | 10061873 | Non-small cell lung cancer | 100000004864 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- Subject is currently receiving treatment with dabrafenib and/or trametinib monotherapy or combination within a Novartis or former GSK sponsored study which has fulfilled the requirements for the primary objective.
- In the opinion of the Investigator would benefit from continued treatment.
- Subject has demonstrated compliance, as assessed by the Investigator, within the parent study protocol requirement(s).
- Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures.
- Written informed consent obtained prior to enrolling in the roll-over study and receiving study medication. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
- Does not require treatment with prohibited concomitant medications.
Exclusion criteria 6
- Subject has been previously permanently discontinued from study treatment in the parent protocol.
- Subject’s indication is commercially available and reimbursed in the local country.
- Subject currently has unresolved toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study. If the patient, in the opinion of the investigator and as per parent protocol, can resume treatment then the patient will be allowed to enroll in CDRB436X2X02B study.
- Female subjects who are lactating, unless they are willing discontinue nursing prior to first dose of study treatment, and willing to refrain from nursing throughout the treatment period and for 4 months following the last dose of study treatment.
- Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception whilst taking study treatment and for 16 weeks after stopping treatment with trametinib (for trametinib monotherapy trials); 2 weeks after stopping treatment with dabrafenib (for dabrafenib monotherapy trials); 16 weeks after stopping treatment with trametinib or 2 weeks after stopping treatment with dabrafenib, whichever is longer (for trials of dabrafenib in combination with trametinib).
- Sexually active males unwilling to use a condom during intercourse whilst taking study treatment and for: 16 weeks after stopping study treatment with dabrafenib in combination with trametinib 2 weeks after stopping study treatment with dabrafenib monotherapy 16 weeks after stopping study treatment with trametinib monotherapy A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Frequency and severity of AEs/SAEs.
Secondary endpoints 1
- Proportion of subjects with clinical benefit as assessed by the Investigator at scheduled visits.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 8
Mekinist 0.5 mg film-coated tablets
PRD3045763 · Product
- Active substance
- Trametinib
- Substance synonyms
- GSK1120212B
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 8760 mg milligram(s)
- Max treatment duration
- 144 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EE01 — -
- Marketing authorisation
- EU/1/14/931/002
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2374
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- - Packaging sites - Bottle fill-count - Storage conditions - Shelf-life - Labelling
Mekinist 2 mg film-coated tablets
PRD3045800 · Product
- Active substance
- Trametinib
- Substance synonyms
- GSK1120212B
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 8760 mg milligram(s)
- Max treatment duration
- 144 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01EE01 — -
- Marketing authorisation
- EU/1/14/931/006
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2374
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Packaging sites - Bottle fill-count - Storage conditions - Shelf-life - Labelling
PRD11337569 · Product
- Active substance
- Dabrafenib Mesylate
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 1080000 mg milligram(s)
- Max treatment duration
- 120 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- NOVARTIS PHARMA AG
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2372
PRD11337575 · Product
- Active substance
- Dabrafenib Mesylate
- Pharmaceutical form
- DISPERSIBLE TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 1314000 mg milligram(s)
- Max treatment duration
- 144 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- NOVARTIS PHARMA AG
- Paediatric formulation
- Yes
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2372
PRD11337573 · Product
- Active substance
- Dabrafenib Mesylate
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 1080000 mg milligram(s)
- Max treatment duration
- 120 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- NOVARTIS PHARMA AG
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2372
PRD10732001 · Product
- Active substance
- Trametinib
- Substance synonyms
- GSK1120212B
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 8760 mg milligram(s)
- Max treatment duration
- 144 Month(s)
- Authorisation status
- Not Authorised
- ATC code
- L01EE01 — -
- MA holder
- NOVARTIS PHARMA AG
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2374
PRD10732002 · Product
- Active substance
- Trametinib
- Substance synonyms
- GSK1120212B
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 8760 mg milligram(s)
- Max treatment duration
- 144 Month(s)
- Authorisation status
- Not Authorised
- ATC code
- L01EE01 — -
- MA holder
- NOVARTIS PHARMA AG
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2374
PRD10466286 · Product
- Active substance
- Trametinib
- Substance synonyms
- GSK1120212B
- Pharmaceutical form
- POWDER FOR ORAL SOLUTION
- Route of administration
- ORAL USE
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 8760 mg milligram(s)
- Max treatment duration
- 144 Month(s)
- Authorisation status
- Not Authorised
- ATC code
- L01EE01 — -
- MA holder
- NOVARTIS PHARMA AG
- Paediatric formulation
- Yes
- Orphan designation
- Yes
- Orphan designation number
- EU/3/20/2374
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Novartis Pharma AG
- Sponsor organisation
- Novartis Pharma AG
- Address
- Lichtstrasse 35
- City
- Basel
- Postcode
- 4056
- Country
- Switzerland
Scientific contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Novartis Pharma Arzneimittel GmbH
Public contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Novartis Pharma Arzneimittel GmbH
Third parties 8
| Organisation | City, country | Duties |
|---|---|---|
| Mag. Andreas Raffeiner GmbH ORG-100043223
|
Walding, Austria | Code 8 |
| Parexel International (IRL) Limited ORG-100022780
|
Dublin 2, Ireland | Code 12 |
| Specific Pharma A/S ORG-100015041
|
Copenhagen Sv, Denmark | Other |
| Abf Pharmaceutical Services GmbH ORG-100014752
|
Vienna, Austria | Other |
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | On site monitoring |
| IQVIA Limited ORG-100008655
|
Reading, United Kingdom | On site monitoring |
| PAREXEL International GmbH ORG-100008131
|
Schoenefeld, Germany | Code 14 |
| Syneos Health Inc. ORG-100008382
|
Morrisville, United States | On site monitoring |
Locations
7 EU/EEA countries · 21 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ongoing, recruiting | 1 | 1 |
| Denmark | Ongoing, recruiting | 1 | 1 |
| France | Ongoing, recruiting | 10 | 4 |
| Germany | Ongoing, recruiting | 6 | 6 |
| Hungary | Ended | 2 | 2 |
| Netherlands | Ongoing, recruiting | 1 | 1 |
| Spain | Ongoing, recruiting | 7 | 6 |
| Rest of world
Korea, Republic of, Canada, United States, Thailand, China, Turkey
|
— | 82 | — |
Investigational sites
Medizinische Universitaet Innsbruck
#3050:Haematology Oncology, Anichstrasse 35, 6020, Innsbruck
Rigshospitalet
#2050:Hæmatologisk afdeling, Blegdamsvej 9, 2100, Copenhagen Oe
Institut Gustave Roussy
#1702:Oncologie pediatrique, 114 Rue Edouard Vaillant, 94800, Villejuif
Institut Curie
#1705:Oncologie pediatrique, 26 Rue D Ulm, 75005, Paris
Centre Hospitalier Universitaire De Nantes
#1703:Hématologie Clinique, 1 Place Alexis Ricordeau, 44000, Nantes
Centre Leon Berard
#1701:Service Oncologie Médicale, 28 Rue Laennec, 69008, Lyon
Universitaetsklinikum Augsburg
2057: Klinik für Kinder- und Jugendmedizin, Stenglinstrasse 2, Kriegshaber, Augsburg
Universitaetsklinikum Essen AöR
2055: Klinik für Kinderheilkunde III, Hufelandstrasse 55, Holsterhausen, Essen
Universitaetsklinikum Mannheim GmbH
2051: Hämatologie und Internistische Onkologie, Theodor-Kutzer-Ufer 1-3, Wohlgelegen, Mannheim
University Medical Center Hamburg-Eppendorf
2056: Klinik für pädiatrische Hämatologie und Onkologie, Martinistrasse 52, Eppendorf, Hamburg
University Medical Center Hamburg-Eppendorf
2053: Zentrum für Onkologie, Martinistrasse 52, Eppendorf, Hamburg
Universitaetsklinikum Heidelberg AöR
2054: Medizinische Klinik V, Im Neuenheimer Feld 410, Neuenheim, Heidelberg
University Of Debrecen
#9502, Nagyerdei Korut 98, 4032, Debrecen
Orszagos Onkologiai Intezet
#9503, Rath Gyorgy Utca 7-9, Kerulet, Budapest XII
Universitair Medisch Centrum Utrecht
#6050:Hematology, Heidelberglaan 100, 3584 CX, Utrecht
Hospital Universitario Hm Sanchinarro
#3102:Oncología médica, Calle Ona 10, 28050, Madrid
Hospital Universitario Fundacion Jimenez Diaz
#3101:Oncología médica, Avenida De Los Reyes Catolicos 2, 28040, Madrid
Hospital Universitari Vall D Hebron
#3100:Oncología médica, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Hospital General Universitario Gregorio Maranon
#3105:Onco Hematología, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Infantil Universitario Nino Jesus
#3104:Onco Hematología, Avenida De Menendez Pelayo 65, 28009, Madrid
Hospital Universitario Y Politecnico La Fe
#3106:Onco Hematología, Avenida Fernando Abril Martorell 106, 46026, Valencia
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 | 2021-08-18 | 2021-08-18 | |||
| Denmark | 2021-09-27 | 2021-09-27 | |||
| France | 2018-01-15 | 2018-01-15 | |||
| Germany | 2021-07-14 | 2021-07-14 | |||
| Hungary | 2019-04-17 | 2025-04-11 | 2019-04-17 | ||
| Netherlands | 2021-09-08 | 2021-09-08 | |||
| Spain | 2018-01-17 | 2018-01-17 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 57 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol - Signature Page_2023-509318-13-00_1_English_Red | 06 |
| Protocol (for publication) | D1_Protocol_2023-509318-13-00_1_English_Red | 06 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements - Country_1_AT_English_NonRed | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements - Country_1_DE_English_Note to Assesor_NonRed | 23Jul2024 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements - Country_1_ES_Spanish_NonRed | 23Sep2024 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements - Country_1_FR_English_Note to Assessor_NonRed | 01 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements - Country_1_FR_NonRed | 00 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements - Country_1_HU_English_NonRed | v1.0 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements - Country_1_NL_English_NonRed | v00 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_Transition Replacement | V5.0 |
| Subject information and informed consent form (for publication) | L1_ICF - Adolescent Assent_1_DE_German_NonRed | v06.05.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Adolescent Assent_1_ES_Spanish_NonRed | v06.00.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Adolescent Assent_1_FR_French_Red | 06.00.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Adolescent Becoming Adult_1_FR_French_Red | 06.05.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Child Assent_1_DE_German_NonRed | v06.05.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Child Assent_1_FR_French_NonRed | 06.00.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for partner and pregnant participant_1_FR_French_NonRed | 06.02.02 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant participant_1_AT_German_NonRed | v2.1 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant participant_1_DE_German_NonRed | 02.01.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant participant_1_ES_Spanish_NonRed | 26Nov2025 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant participant_1_HU_Hungarian_NonRed | 2.0 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant participant_1_NL_Dutch_NonRed | V06020100 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant participant_2_HU_Hungarian_NonRed | 2.0 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant partner of participant_1_AT_German_NonRed | v06.02.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant partner of participant_1_DE_German_NonRed | 02.01.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant partner of participant_1_ES_Spanish_NonRed | 26Nov2025 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant partner of participant_1_HU_Hungarian_NonRed | 2.0 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant partner of participant_1_NL_Dutch_NonRed | V06020101 |
| Subject information and informed consent form (for publication) | L1_ICF - Follow up for pregnant partner of participant_2_HU_Hungarian_NonRed | 2.0 |
| Subject information and informed consent form (for publication) | L1_ICF - Info Sheet Female Partner_1_DE_German_NonRed | 05.04.01 |
| Subject information and informed consent form (for publication) | L1_ICF - Info Sheet Female Partner_1_ES_Spanish_NonRed | v03.01.01 |
| Subject information and informed consent form (for publication) | L1_ICF - Info Sheet Female Partner_1_FR_French_NonRed | V03.01.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Info Sheet Female Partner_1_HU_Hungarian_NonRed | 03.01.03 |
| Subject information and informed consent form (for publication) | L1_ICF - Info Sheet Female Partner_1_NL_Dutch_NonRed | v02010000 |
| Subject information and informed consent form (for publication) | L1_ICF - Main ICF _1_NL_Dutch_NonRed | V06050302 |
| Subject information and informed consent form (for publication) | L1_ICF - Main ICF - Adult_1_AT_German_NonRed | v06.05.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Main ICF - Adult_1_DE_German_NonRed | v06.05.11 |
| Subject information and informed consent form (for publication) | L1_ICF - Main ICF - Adult_1_DK_Danish_Red | V06.05.05 |
| Subject information and informed consent form (for publication) | L1_ICF - Main ICF - Adult_1_ES_Spanish_NonRed | v06.05.07 |
| Subject information and informed consent form (for publication) | L1_ICF - Main ICF - Adult_1_FR_French_Red | 06.05.06 |
| Subject information and informed consent form (for publication) | L1_ICF - Main ICF - Adult_1_HU_Hungarian_Red | 05.04.08 |
| Subject information and informed consent form (for publication) | L1_ICF - Main ICF - Adult_2_HU_Hungarian_NonRed | v05.03.07 |
| Subject information and informed consent form (for publication) | L1_ICF - Main ICF Addendum - Adult_1_FR_French_NonRed | 06.05.08 |
| Subject information and informed consent form (for publication) | L1_ICF - Parent Legal Guardian_1_DE_German_NonRed | v06.05.01 |
| Subject information and informed consent form (for publication) | L1_ICF - Parent Legal Guardian_1_ES_Spanish_NonRed | v06.00.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Parent Legal Guardian_1_FR_French_Red | 06.00.00 |
| Subject information and informed consent form (for publication) | L1_ICF - Pregnancy Follow up Parent Legal Guardian_1_FR_French_NonRed | 06.02.01 |
| Subject information and informed consent form (for publication) | L1_ICF - Separate Data Protection Consent_1_ES_Spanish_NonRed | v3 |
| Subject information and informed consent form (for publication) | L1_ICF - Separate Data Protection Consent_2_ES_Spanish_NonRed | v3 |
| Subject information and informed consent form (for publication) | L1_List of submitted documents_1_HU_NonRed | 30Oct2024 |
| Subject information and informed consent form (for publication) | L2_ICF Procedure_1_DE_English_NonRed | v00 |
| Subject information and informed consent form (for publication) | L2_ICF Procedure_1_ES_Spanish_NonRed | 1Jan1900 |
| Synopsis of the protocol (for publication) | D1_Protocol - Protocol Summary in Technical Language_2023-509318-13-00_1_Hungarian_NonRed | 01Feb2024 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Technical Language_2023-509318-13-00_1_Dutch_NonRed | V01 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Technical Language_2023-509318-13-00_1_French_Red | 06 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Technical Language_2023-509318-13-00_1_German_NonRed | v06 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Technical Language_2023-509318-13-00_1_Spanish_NonRed | V06 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-10 | Spain | Acceptable with conditions 2024-08-01
|
2024-08-01 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-11-26 | Spain | Acceptable 2025-01-30
|
2025-01-30 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-03-06 | Spain | Acceptable | 2025-03-18 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-08-01 | Spain | Acceptable | 2025-08-01 |
| 5 | SUBSTANTIAL MODIFICATION | SM-3 | 2026-02-13 | Spain | Acceptable with conditions 2026-05-13
|
2026-05-13 |