NCT07440290

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 (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.

• Status: Not Yet Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Cancer Research UK · Academic / Other
• Sex: All
• Age: 1 Year
• Healthy volunteers: Not accepted

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.

Detailed description

DETERMINE Treatment Arm 07 (dabrafenib and trametinib) aims to evaluate the efficacy of dabrafenib and trametinib adult, paediatric and TYA patients with rare\* cancers with BRAF V600 mutations or with common cancers where BRAF V600 mutations are considered to be infrequent. \*Rare is defined generally as incidence less than 6 cases in 100,000 patients (includes paediatric and teenagers/young adult cancers) or common cancers with rare alterations. This treatment arm has a target sample size of 30 evaluable patients. Sub-cohorts may be defined and further expanded to a target of 30 evaluable patients each. The ultimate aim is to translate positive clinical findings to the NHS (Cancer Drugs Fund) to provide new treatment options for rare adult, paediatric and TYA cancers. OUTLINE: Pre-screening: The Molecular Tumour Board makes a treatment recommendation for the patient based on molecularly-defined cohorts (See information on Master Screening Protocol below). Screening: Consenting patients undergo biopsy and collection of blood samples for research purposes. Treatment: Patients will receive dabrafenib and trametinib until disease progression without clinical benefit, unacceptable adverse events (AEs) or withdrawal of consent. Patients will also undergo collection of blood samples at various intervals while receiving treatment and at End of Treatment (EoT). After completion of study treatment, patients are followed up every 3 months for 2 years. THE DETERMINE TRIAL MASTER (SCREENING) PROTOCOL: Please see DETERMINE Trial Master (Screening) Protocol record (NCT05722886) for information on the DETERMINE Trial Master Protocol and applicable documents.

Conditions

• Haematological Malignancy
• Malignant Neoplasm
• Lymphoproliferative Disorders
• Neoplasms by Histologic Type
• Neoplasms by Site
• Gastrointestinal Cancer
• Non-Melanoma Skin Cancer (NMSC)
• Langerhans Cell Histiocytosis (LCH)
• Cancer
• Erdheim-Chester Disease
• Thyroid Carcinoma, Papillary
• Ovarian Neoplasms
• Colorectal Neoplasms
• Laryngeal Neoplasms
• Carcinoma, Non-Small Cell-Lung
• Glioma
• Multiple Myeloma
• Thyroid Carcinoma, Anaplastic
• Solid Tumour

Interventions

Type	Name	Description
DRUG	Dabrafenib	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.
DRUG	Trametinib	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.

Timeline

• Start date: 2026-02-01
• Primary completion: 2029-10-01
• Completion: 2029-10-01
• First posted: 2026-02-27
• Last updated: 2026-02-27

Locations

27 sites across 1 country: United Kingdom