DETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage/Young Adult Patients With BRAF V600 Mutation-Positive Cancers.
DETERMINE
DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage/Young Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and TYA Patients With BRAF V600 Mutation-Positive Cancers.
1 other identifier
interventional
30
1 country
27
Brief Summary
This clinical trial is looking at two drugs called dabrafenib and trametinib. Dabrafenib and trametinib are approved as standard of care treatment for adult patients with melanoma (a type of skin cancer) or lung cancer and in children with glioma (a type of brain tumour). This means they have gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Dabrafenib and trametinib work in patients with a particular mutation in their cancer known as BRAF V600. Investigators now wish to find out if they will be useful in treating patients with other cancer types which have the same mutation. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future. This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2026
Typical duration for phase_2
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2026
CompletedFirst Submitted
Initial submission to the registry
February 23, 2026
CompletedFirst Posted
Study publicly available on registry
February 27, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2029
February 27, 2026
February 1, 2026
3.7 years
February 23, 2026
February 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Objective response (OR)
OR is defined as the confirmed occurrence of either a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria (or immune \[i\]RECIST or standard imaging criteria for specific disease e.g. Response Evaluation in Neuro Oncology criteria \[RANO\]). In patients with leukaemia, OR will be defined as the occurrence of CR, CRi (CR with incomplete neutrophil recovery) or CRp (CR with incomplete platelet recovery). The trial will report the proportion of patients with an OR and 95% credible interval.
Disease assessments to be performed up to 24 weeks from the start of trial treatment.
Durable Clinical Benefit (DCB)
DCB is defined as the absence of disease progression for at least 24 weeks from the start of trial treatment according to RECIST Version 1.1 criteria (or iRECIST or standard imaging criteria for specific disease e.g. RANO criteria) and, where relevant (e.g. for haematological malignancies), by standard bone marrow response criteria. Alternative definitions of DCB based on different time points may be pre-specified for particular sub-cohorts if 24 weeks is not clinically relevant. The trial will report the proportion of patients with a DCB and 95% credible interval.
Disease assessments to be performed up to 24 weeks from the start of trial treatment.
Secondary Outcomes (13)
Duration of response (DR)
Disease assessment performed every 2 cycles (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose, for up to 2 years.
Best percentage change in sum of target lesion/index lesion diameters (PCSD)
Disease assessment performed every 2 cycles (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose, for up to 2 years.
Time to treatment discontinuation (TTD)
From first dose of dabrafenib and trametinib to discontinuation of trial treatment up to 5 years.
Progression-Free Survival time (PFS)
Disease assessment performed every 2 cycles (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose, for up to 2 years.
Time to Progression (TTP)
Disease assessment performed every 2 cycles (each cycle is 28 days) and at EoT. After 24 weeks, it can be done every 12 weeks, on discussion with Sponsor. Follow-up visits are every 3 months after last dose, for up to 2 years.
- +8 more secondary outcomes
Study Arms (1)
Treatment Arm 07: Dabrafenib and Trametinib
EXPERIMENTALThis dabrafenib and trametinib treatment arm is for adult, paediatric and TYA patients with cancers harbouring BRAF V600 mutations.
Interventions
Adult patients (≥18 years) will receive dabrafenib at a dose of 150 mg (two 75 mg tablets) twice daily (total daily dose 300 mg) throughout each 28-day cycle. Paediatric patients (1 to \<12 years) will receive dabrafenib dose adjusted by body weight as 10 mg dispersible tablets orally twice daily throughout each 28-day cycle. Paediatric patients (12-15 years) and TYA patients (16 to \<18 years) will have the option to receive adult or paediatric dosing. Patients may continue until disease progression without clinical benefit, unacceptable AEs or withdrawal of consent.
Adult patients (≥18 years) will receive trametinib at a daily dose of 2 mg (one 2 mg tablet) orally once daily (total daily dose 2 mg) throughout the 28-day cycle. Paediatric patients (1 to \<12 years) receive trametinib at a dose adjusted by body weight as 0.05 mg/m\^2 powder for oral solution once daily throughout each 28-day cycle. Paediatric patients (12-15 years) and TYA patients (16 to \<18 years) will have the option to receive adult or paediatric dosing. Patients may continue until disease progression without clinical benefit, unacceptable toxicity or withdrawal of consent.
Eligibility Criteria
You may not qualify if:
- A. Confirmed diagnosis of a malignancy harbouring an oncogenic alteration in BRAF V600, including Langerhans cell histiocytosis, using an analytically validated next-generation sequencing method.
- B. Patients ≥1 year old and ≥8 kg in body weight.
- C. Women of childbearing potential are eligible provided that they meet the following criteria:
- Have a negative serum or urine pregnancy test before enrolment and;
- Agree to use one form of a non-hormonal highly effective contraception method (a method that can achieve a failure rate of \<1% when used consistently and correctly; the requirement for non-hormonal method is because dabrafenib may decrease the efficacy of oral or any systemic hormonal contraceptives), such as: i. intrauterine device (IUD), ii. bilateral tubal occlusion, bilateral tubal ligation (at least six weeks before taking trial treatment), iii. vasectomised partner, iv. total sexual abstinence. Effective from the first administration of dabrafenib and trametinib (whichever is first), throughout the trial and for two weeks following discontinuation of dabrafenib and for 16 weeks following discontinuation of trametinib (whichever is later).
- Patients who are breastfeeding must be willing to discontinue breastfeeding from the start of treatment, throughout the trial and for two weeks following discontinuation of dabrafenib and for 16 weeks following discontinuation of trametinib (whichever is later).
- D. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of dabrafenib and trametinib (whichever is first), throughout the trial and for two weeks after the last administration of dabrafenib and 16 weeks after the last administration of trametinib (whichever is later):
- Agree to take measures not to father children by using a barrier method of contraception (male condom plus spermicide) or to sexual abstinence.
- Non-vasectomised male partners with partners who are women of childbearing potential should also be advised of the benefit for their partner of using a highly effective method of contraception, such as:
- i. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation \[oral, intravaginal or transdermal\]), ii. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), iii. IUD, iv. intrauterine hormone-releasing system (IUS), v. bilateral tubal occlusion, vi. total sexual abstinence.
- Male patients with pregnant or breastfeeding partners must be advised to use barrier method contraception (male condom) to prevent drug exposure of the foetus or neonate, even if vasectomised.
- Male patients must refrain from donating sperm for the same period.
- E. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and/or trephine or lymph node biopsy samples may be taken.
- F. Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility
- A. Diagnosis of one of the following BRAF V600E mutation-positive cancers:
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Cancer Research UKlead
- University of Manchestercollaborator
- University of Birminghamcollaborator
- Novartis Pharmaceuticals UK Limitedcollaborator
- Royal Marsden Hospital NHS Foundation Trust & The Institute of Cancer Researchcollaborator
Study Sites (27)
Belfast City Hospital
Belfast, BT9 7AB, United Kingdom
University Hospital Birmingham
Birmingham, B15 2TT, United Kingdom
Birmingham Children's Hospital
Birmingham, B4 6NH, United Kingdom
Bristol Royal Hospital for Children
Bristol, BS2 8BJ, United Kingdom
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED, United Kingdom
Addenbrooke's Hospital
Cambridge, CB2 OQQ, United Kingdom
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
Cardiff Children's Hospital
Cardiff, CF14 4XW, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
The Beatson Hospital
Glasgow, G12 OYN, United Kingdom
Royal Hospital for Children Glasgow
Glasgow, G51 4TF, United Kingdom
Leicester Royal Infirmary
Leicester, LE1 5WW, United Kingdom
Alder Hey Hospital
Liverpool, L14 5AB, United Kingdom
University College London Hospital
London, NW1 2BU, United Kingdom
Guy's Hopsital
London, SE1 9RT, United Kingdom
Great Ormond Street Hospital
London, WC1N 3JH, United Kingdom
Royal Manchester Children's Hospital
Manchester, M13 9WL, United Kingdom
The Christie Hospital
Manchester, M20 4BX, United Kingdom
Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Great North Children's Hospital
Newcastle, NE1 4LP, United Kingdom
Freeman Hospital
Newcastle, NE7 7DN, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
John Radcliffe Hospital
Oxford, OX3 9DU, United Kingdom
Weston Park Hospital
Sheffield, S10 2SJ, United Kingdom
Sheffield's Children's Hospital
Sheffield, S10 2TH, United Kingdom
Southampton General Hospital
Southampton, United Kingdom
The Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew Krebs
The Christie Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 23, 2026
First Posted
February 27, 2026
Study Start
February 1, 2026
Primary Completion (Estimated)
October 1, 2029
Study Completion (Estimated)
October 1, 2029
Last Updated
February 27, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- All requests for data relating to this treatment arm that are made within 5 years from last patient last visit for the dabrafenib and trametinib treatment arm will be considered; requests made subsequently will be considered where possible.
- Access Criteria
- When a request has been approved, Cancer Research UK will provide access to the de-identified individual patient-level data and appropriate supporting information. A signed Data Sharing Agreement must be in place before accessing requested information. Requests should be submitted to drugdev@cancer.org.uk.
Individual de-identified patient data will be shared with researchers whose proposed use of the data is approved by a review committee of the Sponsor. Supporting Information: Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF)