DETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage/Young Adult Patients With BRAF V600 Mutation-Positive Cancers.

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.

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

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.

Sponsors & Collaborators

• University of Manchester

  collaborator OTHER

• University of Birmingham

  collaborator OTHER

• Novartis Pharmaceuticals UK Limited

  collaborator UNKNOWN

• Royal Marsden Hospital NHS Foundation Trust & The Institute of Cancer Research

  collaborator UNKNOWN

• Cancer Research UK

  lead OTHER

Principal Investigators

• Matthew Krebs · The Christie Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-28

Primary Completion

2029-10-31

Completion

2029-10-31

Countries

• United Kingdom

Study Locations