Clinical trial • Phase IV • Oncology
Dabrafenib mesylate for BRAF V600-mutant cancers
Phase IV trial of Dabrafenib mesylate for BRAF V600-mutant cancers. open-label. 98 participants.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- BRAF V600-mutant cancers
- Trial Stage
- Phase IV
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 21-06-2024
- First CTIS Authorization Date
- 19-07-2024
Trial design
open-label Phase IV trial across 27 sites in Netherlands, Czechia, Finland and others.
- Open Label
- Yes
- Biomarker Stratified
- True, BRAF V600 mutation
- Target Sample Size
- 98
Eligibility
Recruits 98 paediatric patients.
- Pregnancy Exclusion
- Women of childbearing potential, defined as all females physiologically capable of becoming pregnant, must continue to use highly effective form of birth control method (contraception) during the study and for 16 weeks after stopping treatment with trametinib monotherapy or dabrafenib in combination with trametinib, and 2 weeks after stopping treatment with dabrafenib monotherapy, whichever is longer. a. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (i.e. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. b. Female bilateral tube ligation, female sterilization, surgically sterilized prior to the study (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when reproductive status of woman has been confirmed by follow-up hormone level assessment. c. Sterilization (at least 6 months prior to screening) for male partners. The sterilized male partner should be the sole partner for that subject. d. For subjects on dabrafenib monotherapy / trametinib in combination with dabrafenib: Placement of a hormonal or non-hormonal intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year. e. For subjects on trametinib monotherapy: Use of oral (estrogen and progesterone), injected or implanted combined hormonal methods of contraception, or placement of an intrauterine device (IUD), or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Male subjects (including those that have had a vasectomy) not willing to use a condom during intercourse while taking trametinib and/or dabrafenib and for the period of 16 weeks (for patients taking trametinib only, or in combination) or 2 weeks (for patients taking dabrafenib only) following stopping of study treatment. 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. Notes: • Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository) are not considered highly effective methods of contraception. • Hormonal-based methods (i.e. oral contraceptives) are not considered as highly effective methods of contraception for patients taking dabrafenib due to potential drugdrug interactions with dabrafenib. • If local regulations are more stringent than the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF
- Vulnerable Population
- Pediatric patients are included. Written informed consent must be obtained, according to local guidelines, signed by the subject and/or by the parents or legal guardian prior to any study-related screening procedures. Assent forms and age-appropriate ICFs are provided (documents listed for parent/legal guardian, adolescent assent, pre-adolescent assent, child assent) indicating assent/consent handling for minors per local requirements.
Inclusion criteria
- {"criterion_text":"- Written informed consent, according to local guidelines, signed by the subject and/or by the parents or legal guardian prior to any study related screening procedures are performed."}
- {"criterion_text":"- Current or prior participation in a Novartis sponsored study such as CTMT212X2101, CDRB436G2201, CDRB436A2102, regardless of current age and independent of study phase."}
- {"criterion_text":"- Parent study (or cohort of parent study) is planned to be closed."}
- {"criterion_text":"- Subject has demonstrated treatment compliance, as assessed by the Investigator, within the parent study protocol requirement(s)."}
- {"criterion_text":"- Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures."}
- {"criterion_text":"- Subject is currently receiving treatment with dabrafenib and/or trametinib within a Novartis Sponsored Drug Development study (i.e. CTMT212X2101, CDRB436G2201, CDRB436A2102)"}
- {"criterion_text":"- In the opinion of the Investigator is likely to benefit from continued treatment."}
- {"criterion_text":"- Does not require treatment with prohibited concomitant medications."}
Exclusion criteria
- {"criterion_text":"- Subject has participated in a combination trial where dabrafenib and/or trametinib was dispensed in combination with another study medication. (Exception: Patients who were on the chemotherapy arm of the CDRB436G2201 study are eligible for this study after crossing over into the experimental treatment arm of the CDRB436G2201 study or have discontinued the study treatment and are now in follow-up)."}
- {"criterion_text":"- Subject has permanently discontinued from study treatment in the parent protocol due to any reason."}
- {"criterion_text":"- Treatment with dabrafenib and/or trametinib for the patient’s indication is approved for marketing and the appropriate dosage form is commercially available and reimbursed in the country."}
- {"criterion_text":"- Subject currently has unresolved drug related severe toxicities for which dabrafenib and/or trametinib dosing has been interrupted in the parent study. If the subject should meet criteria to resume treatment on the parent protocol then they may be eligible for enrolment in this study."}
- {"criterion_text":"- Women of childbearing potential, defined as all females physiologically capable of becoming pregnant, must continue to use highly effective form of birth control method (contraception) during the study and for 16 weeks after stopping treatment with trametinib monotherapy or dabrafenib in combination with trametinib, and 2 weeks after stopping treatment with dabrafenib monotherapy, whichever is longer. a. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (i.e. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. b. Female bilateral tube ligation, female sterilization, surgically sterilized prior to the study (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when reproductive status of woman has been confirmed by follow-up hormone level assessment. c. Sterilization (at least 6 months prior to screening) for male partners. The sterilized male partner should be the sole partner for that subject. d. For subjects on dabrafenib monotherapy / trametinib in combination with dabrafenib: Placement of a hormonal or non-hormonal intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year. e. For subjects on trametinib monotherapy: Use of oral (estrogen and progesterone), injected or implanted combined hormonal methods of contraception, or placement of an intrauterine device (IUD), or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Male subjects (including those that have had a vasectomy) not willing to use a condom during intercourse while taking trametinib and/or dabrafenib and for the period of 16 weeks (for patients taking trametinib only, or in combination) or 2 weeks (for patients taking dabrafenib only) following stopping of study treatment. 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. Notes: •\tDouble-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository) are not considered highly effective methods of contraception. •\tHormonal-based methods (i.e. oral contraceptives) are not considered as highly effective methods of contraception for patients taking dabrafenib due to potential drugdrug interactions with dabrafenib. •\tIf local regulations are more stringent than the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF"}
- {"criterion_text":"- Lactating females who are actively breast feeding."}
- {"criterion_text":"- Concurrent participation in other clinical trials using experimental therapies."}
Endpoints
Primary endpoints
- {"endpoint_text":"- AEs, SAE, clinically significant changes in laboratory values and vital signs.","definition_or_measurement_approach":"Adverse events (AEs) and serious adverse events (SAEs) reported per standard safety reporting; clinically significant laboratory value changes and vital signs assessed using routine clinical laboratory tests and vital sign measurements. No further detailed definition provided in the available record."}
Secondary endpoints
- {"endpoint_text":"- Serial measurements of height, weight, skeletal maturation, sexual maturation and cardiac function.","definition_or_measurement_approach":"Serial clinical measurements (height, weight), assessments of skeletal and sexual maturation and cardiac function over time; measured per institutional procedures. No detailed assessment schedules provided in the available record."}
- {"endpoint_text":"- Disease specific clinical benefit, as determined by investigator using institutional standard of care.","definition_or_measurement_approach":"Clinical benefit determined by the investigator using institutional standard-of-care procedures (investigator-assessed disease-specific benefit)."}
Recruitment
- Planned Sample Size
- 98
- Recruitment Window Months
- 78
- Consent Approach
- Written informed consent, according to local guidelines, signed by the subject and/or by the parents or legal guardian prior to any study related screening procedures. Age-appropriate assent forms and separate ICFs for parents/legal guardians, adolescents, pre-adolescents and children are available (country-specific ICF documents listed in the record).
Geography
- Total Number Of Sites
- 27
- Total Number Of Participants
- 68
Netherlands
- Latest Decision Or Authorization Date
- 19-07-2024
- Number Of Sites
- 1
- Number Of Participants
- 3
Sites
- Site Name
- Prinses Maxima Centrum voor Kinderoncologie B.V.
- Department Name
- 3401:Pediatric oncology
- Contact Person Name
- Jasper van der Lugt
- Contact Person Email
- j.vanderlugt@prinsesmaximacentrum.nl
Czechia
- Latest Decision Or Authorization Date
- 24-07-2024
- Number Of Sites
- 2
- Number Of Participants
- 3
Sites
- Site Name
- Fakultni Nemocnice V Motole
- Department Name
- 1502: Klinika detske hematologie a onkologie
- Contact Person Name
- David Sumerauer
- Contact Person Email
- David.sumeraurer@fnmotol.cz
- Site Name
- Fakultni Nemocnice Brno
- Department Name
- 1501: Klinika detske onkologie
- Contact Person Name
- Zdenek Pavelka
- Contact Person Email
- pavelka.zdenek@fnbrno.cz
Finland
- Latest Decision Or Authorization Date
- 23-07-2024
- Number Of Sites
- 1
- Number Of Participants
- 2
Sites
- Site Name
- Tampere University Hospital
- Department Name
- 1801:Department of Paediatrics and Adolescent Medicine
- Contact Person Name
- Olli Lohi
- Contact Person Email
- olli.lohi@pirha.fi
Denmark
- Latest Decision Or Authorization Date
- 25-07-2024
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Rigshospitalet
- Department Name
- 1601: Klinisk Forsøgsenhed for Børn og Unge med Kræft afsnit 5092
- Contact Person Name
- Karsten Nysom
- Contact Person Email
- karsten.nysom@regionh.dk
Belgium
- Latest Decision Or Authorization Date
- 23-07-2024
- Number Of Sites
- 1
- Number Of Participants
- 1
Sites
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- 1201: Pediatric oncology – hematology
- Contact Person Name
- An Van Damme
- Contact Person Email
- an.vandamme@uclouvain.be
Spain
- Latest Decision Or Authorization Date
- 24-07-2024
- Number Of Sites
- 3
- Number Of Participants
- 7
Sites
- Site Name
- Hospital Infantil Universitario Nino Jesus
- Department Name
- 2301:Oncología
- Contact Person Name
- Alba Rubio San Simon
- Contact Person Email
- alba.rubio@salud.madrid.org
- Site Name
- Hospital Universitario Y Politecnico La Fe
- Department Name
- 2303:Oncología
- Contact Person Name
- Adela Cañete Nieto
- Contact Person Email
- canyete_ade@gva.es
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- 2302:Onco-hematología pediátrica
- Contact Person Name
- David Díaz Pérez
- Contact Person Email
- ddiazp@salud.madrid.org
Italy
- Latest Decision Or Authorization Date
- 05-08-2024
- Number Of Sites
- 5
- Number Of Participants
- 16
Sites
- Site Name
- Azienda Ospedaliera Universitaria Meyer IRCCS
- Department Name
- 3804:U.O. Neuro-Oncologia
- Contact Person Name
- Carla Fonte
- Contact Person Email
- carla.fonte@meyer.it
- Site Name
- Fondazione IRCCS Istituto Nazionale Dei Tumori
- Department Name
- 3800:S.C. Pediatria Oncologica
- Contact Person Name
- Elisabetta Schiavello
- Contact Person Email
- elisabetta.schiavello@istitutotumori.mi.it
- Site Name
- Ospedale Pediatrico Bambino Gesu
- Department Name
- 3802:Dipartimento di Onco-Ematologia, Terapia cellulare, terapie geniche e trapianto emopoietico
- Contact Person Name
- Franco Locatelli
- Contact Person Email
- franco.locatelli@opbg.net
- Site Name
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
- Department Name
- 3803:S.C. Oncoematologia Pediatrica
- Contact Person Name
- Franca Fagioli
- Contact Person Email
- franca.fagioli@unito.it
- Site Name
- IRCCS Istituto Giannina Gaslini
- Department Name
- 3801:U.O.S.D. Neuro-Oncologia
- Contact Person Name
- Antonio Verrico
- Contact Person Email
- antonioverrico@gaslini.org
Germany
- Latest Decision Or Authorization Date
- 23-07-2024
- Number Of Sites
- 5
- Number Of Participants
- 8
Sites
- Site Name
- University Medical Center Hamburg-Eppendorf
- Department Name
- 1904:Klinik für pädiatrische Hämatologie und Onkologie
- Contact Person Name
- Uwe Kordes
- Contact Person Email
- u.kordes@uke.de
- Site Name
- University Hospital Cologne AöR
- Department Name
- 1902: Klinik und Poliklinik für Kinder- und Jugendmedizin
- Contact Person Name
- Matthias Fischer
- Contact Person Email
- matthias.fischer@uk-koeln.de
- Site Name
- Universitaetsklinikum Augsburg
- Department Name
- 1906:Klinik für Kinder- und Jugendmedizin
- Contact Person Name
- Michael Fruehwald
- Contact Person Email
- Michael.Fruehwald@uk-augsburg.de
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- 1903:Klinik für Kinderheilkunde III
- Contact Person Name
- Stephan Tippelt
- Contact Person Email
- stephan.tippelt@uk-essen.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- 1905: Klinik für Pädiatrie mit Schwerpunkt Onkologie/Hämatologie
- Contact Person Name
- Pablo Hernaiz-Driever
- Contact Person Email
- pablo.hernaiz@charite.de
Sweden
- Latest Decision Or Authorization Date
- 22-07-2024
- Number Of Sites
- 1
- Number Of Participants
- 4
Sites
- Site Name
- Karolinska University Hospital
- Department Name
- 2401: Barnonkologen
- Contact Person Name
- Tomas Sjöberg Bexelius
- Contact Person Email
- tomas.sjoberg-bexelius@regionstockholm.se
France
- Latest Decision Or Authorization Date
- 23-07-2024
- Number Of Sites
- 7
- Number Of Participants
- 20
Sites
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- 1703: Oncology/Hematology
- Contact Person Name
- Nicolas Andre
- Contact Person Email
- nicolas.andre@ap-hm.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- 1705: Pediatric Oncology/Hematology
- Contact Person Name
- Jamie Probert
- Contact Person Email
- jamie.probert@chu-rennes.fr
- Site Name
- CHRU De Nancy
- Department Name
- 1704: Pediatric Oncology/Hematology
- Contact Person Name
- Marie Sophie Merlin
- Contact Person Email
- M.MERLIN@chru-nancy.fr
- Site Name
- Centre Hospitalier Regional Et Universitaire De Brest
- Department Name
- 1706: Pediatrics
- Contact Person Name
- Chloe Henry
- Contact Person Email
- chloe.henry@chu-brest.fr
- Site Name
- Institut Gustave Roussy
- Department Name
- 1702: Pediatrics
- Contact Person Name
- Pablo Berlanga
- Contact Person Email
- pablo.berlanga@gustaveroussy.fr
- Site Name
- Institut Curie
- Department Name
- 1701: Pediatric Oncology
- Contact Person Name
- Isabelle Aerts
- Contact Person Email
- isabelle.aerts@curie.fr
- Site Name
- Centre Hospitalier Universitaire De Rennes
- Department Name
- 1707: Dermatology
- Contact Person Name
- Henri Adamski
- Contact Person Email
- henri.adamski@chu-rennes.fr
Sponsor
Primary sponsor
- Full Name
- Novartis Pharma AG
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Switzerland
Contract research organisations
- Name
- Icon Clinical Research Limited
- Responsibilities
- sponsorDuties codes: [1]
- Name
- Syneos Health Inc.
- Responsibilities
- sponsorDuties codes: [1]
- Name
- IQVIA Limited
- Responsibilities
- sponsorDuties codes: [1, 3]
- Name
- Parexel International (IRL) Limited
- Responsibilities
- sponsorDuties codes: [12, 15] (includes ancillary supplies)
Third parties
- {"country":"United States","full_name":"Labcorp Early Development Laboratories Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
- {"country":"Denmark","full_name":"Specific Pharma A/S","duties_or_roles":"Pass-through warehouse (drug distribution, drug return, destruction and relabeling) (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: [1]","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties codes: [1]","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: [1, 3]","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"Drug distribution, storage, relabeling, return and destruction (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
- {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Laboratory kits, transportation, sample storage (sponsorDuties code: 15)","organisation_type":"Pharmaceutical company"}
- {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: [12, 15] (Ancillary supplies)","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- DRB436 (dabrafenib)
- Active Substance
- Dabrafenib mesylate
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL
- Authorisation Status
- prodAuthStatus: 1
- Orphan Designation
- Yes
- Maximum Dose
- 300 mg (maxDailyDoseAmount: 300)
- Investigational Product Name
- TMT212 / Mekinist (trametinib)
- Active Substance
- Trametinib (trametinib dimethyl sulfoxide)
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- ORAL
- Authorisation Status
- prodAuthStatus: 1 (some marketed variants with prodAuthStatus: 2 and marketing authorisation numbers listed for commercial products)
- Orphan Designation
- Yes
- Maximum Dose
- 2 mg (maxDailyDoseAmount: 2)
- Combination Treatment
- Yes
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