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

ConditionsHaematological MalignancyMalignant NeoplasmLymphoproliferative DisordersNeoplasms by Histologic TypeNeoplasms by SiteGastrointestinal CancerNon-Melanoma Skin Cancer (NMSC)Langerhans Cell Histiocytosis (LCH)CancerErdheim-Chester DiseaseThyroid Carcinoma, PapillaryOvarian NeoplasmsColorectal NeoplasmsLaryngeal NeoplasmsCarcinoma, Non-Small Cell-LungGliomaMultiple MyelomaThyroid Carcinoma, AnaplasticSolid TumourPancreatic Diseases
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age1+
SponsorCancer Research UK

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

None

Disqualifiers

Agree to take measures not to father children by using a barrier method of contraception (male condom plus spermicide) or to 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.

Colorectal cancer in adult (≥18 years) patients;

Trial design

Design model

Single group

Treatments tested in this trial

  • Dabrafenib

    Drug

    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.

  • Trametinib

    Drug

    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.

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: Treatment Arm 07: Dabrafenib and TrametinibExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Disease assessments to be performed up to 24 weeks from the start of trial treatment.
2

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.

Time frame
Disease assessments to be performed up to 24 weeks from the start of trial treatment.

Secondary outcomes

1

Duration of response (DR)

DR is defined as the time from the date of the first confirmed CR or PR according to RECIST Version 1.1 criteria (or iRECIST) or standard imaging criteria for specific disease. The trial will report the median DR and 95% credible interval.

Time frame
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.
2

Best percentage change in sum of target lesion/index lesion diameters (PCSD)

PCSD is defined as the greatest decrease or least increase in the sum of target lesion diameters (RECIST) or index lesion diameters (iRECIST) as a percentage compared to the baseline measurement. The trial will report the mean PCSD and 95% credible interval.

Time frame
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.
3

Time to treatment discontinuation (TTD)

TTD is defined as the time from date of starting trial treatment to date of discontinuing trial treatment, in days estimated by the median of the posterior inverse gamma probability distribution. The trial will report the median TTD and 95% credible interval.

Time frame
From first dose of dabrafenib and trametinib to discontinuation of trial treatment up to 5 years.
4

Progression-Free Survival time (PFS)

PFS is defined as the time from date of starting trial treatment to date of progression or date of death without a previous progression recorded estimated by the median of the posterior inverse gamma probability distribution.

Time frame
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.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Cancer Research UK

Lead sponsor

University of Manchester

Collaborator

University of Birmingham

Collaborator

Novartis Pharmaceuticals UK Limited

Collaborator

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

Collaborator

Source ClinicalTrials.gov
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