Phase II clinical trial, with two cohorts of patients included in parallel, all with melanoma BRAF mutated and brain metastases without previous local treatment in the brain. Cohort 1 will include patients with asymptomatic brain metastases and cohort 2 will include patients with symptomatic brain metastasis.
Name: encorafenib
Description: Encorafenib 75mg and 50mg (capsules) for a 450mg daily for oral administration during 56 days and after local radiation treatment. If no progression of disease progression (PD) is reported, treatment will continue until PD, unacceptable toxicity or death.Type: DrugCOMBO450
Name: binimetinib
Description: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment.Type: DrugCOMBO450
Name: Whole brain radiation therapy
Description: The whole brain planning target volume (PTV) will receive 30 Gy in 10 fractions. Treatment will be delivered once daily, 5 fractions per week, over 2 to 2.5 weeks.Type: RadiationCOMBO450
Name: Radiosurgery/stereotactic radiosurgery
Description: Dose selection must be based on previously published Radiation Therapy Oncology Group (RTOG) data, with dose modification left up to the treating physician. The total dose will depend on the size of the metastatic lesion(s) and proximity to critical structures. Suggested doses are as follow: 1 fraction x 15-25 Gy; 3 fractions x 9-11 Gy; 5 fractions x 6-7 Gy; or 6 fractions x 5-6 Gy. For GTV > 20 mm hypofractionated stereotactic radiotherapy could be preferred. Treatment will be delivered once daily, alternate-day, 3 fractions per week.Type: RadiationCOMBO450
Description: iORR calculated as the proportion of patient with a best overall intracranial response of complete response (CR) or partial response (PR) before local treatment in cohort 1. The final statistical analysis of this endpoint is expected to be performed within 3 months after the local treatment of the last patient in cohort 1. This outcome will be assessed on day 56, and every 8 weeks up to 24 months after start of treatment
Measure: Intracranial objective response by RECIST 1.1 before local radiotherapy treatment in cohort 1 Time: 24 months after start of treatmentDescription: ORR calculated as the proportion of patient with a best overall intracranial response of complete response (CR) or partial response (PR) before local treatment in cohort 1. The final statistical analysis of this endpoint is expected to be performed within 3 months after the local treatment of the last patient in cohort 2. This outcome will be assessed on day 56, and every 8 weeks up to 24 months after start of treatment
Measure: Intracranial objective response by RECIST 1.1 before local radiotherapy treatment in cohort 2 Time: 24 months after start of treatmentDescription: Compared to baseline evaluation evaluated after 8 weeks since the start of treatment
Measure: Change on Quality of life at week 8 in both cohorts based on the EORTC QLQ 30 scale Time: 8 weeksDescription: Compared to baseline evaluation evaluated after 24 weeks since the start of treatment
Measure: Change on Quality of life at week 24 in both cohorts based on the EORTC QLQ 30 scale Time: 24 weeksSingle Group Assignment
There are 2 SNPs
- Histologically confirmed diagnosis of unresectable metastatic cutaneous melanoma, or unknown primary melanoma with one or more brain metastasis with a diameter of 10 to 50 mm, measured by contrast enhanced MRI. - Presence of a BRAF V600E or V600K mutation, or both, in their tumour tissue. --- V600E ---
- Histologically confirmed diagnosis of unresectable metastatic cutaneous melanoma, or unknown primary melanoma with one or more brain metastasis with a diameter of 10 to 50 mm, measured by contrast enhanced MRI. - Presence of a BRAF V600E or V600K mutation, or both, in their tumour tissue. --- V600E --- --- V600K ---