| Primary | Intracranial Objective Response (iORR) by Modified RECIST 1.1 Before Local Radiotherapy Treatment in Full Dataset | iORR calculated as the proportion of patient with a best overall intracranial response of complete response (CR) or partial response (PR) before local treatment according to modified RECIST 1.1. Modified RECIST 1.1 consists of: Up to 5 intracranial lesions could be selected as target lesions Target lesions might have a longest diameter ≥ 5 mm when evaluated by contrast-enhanced MRI This endpoint was also independently reported in patients with symptomatic and asymptomatic brain metastasis. | The endpoint is calculated for the full dataset and also in two subgroups with symptomatic or asymptomatic brain metastasis, respectively. | Posted | | Count of Participants | | Participants | | 24 months after start of treatment | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Full analysis set | | | Title | Measurements |
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| Patients with intracranial response | | | Patients with NO intracranial response | |
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| Secondary | Duration of Intracranial Response | Calculated as the time from the date of first documented CR or PR to the first documented intracranial progression or death due to underlying cancer accoridng to modified RECIST 1.1, in patients with documented intracranial CR or PR before local treatment. | Only patients who have an intracranial responses were analyzed for its duration. | Posted | | Median | 95% Confidence Interval | months | | Throughout the study period, up to approximately 24 months | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Secondary | Intracranial Progression-free Survival (iPFS) by RECIST 1.1 | Defined as the time from the date of inclusion to the date of the first documented intracranial disease progression or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (modified RECIST version 1.1 criteria). The local Investigator's assessments was used for analyses. Those patients who were alive and had not progressed at the last follow-up, date of progression was censored at the date of the last follow-up. Patients with no additional image test other than baseline were censored the day after inclusion. | | Posted | | Median | 95% Confidence Interval | months | | Throughout the study period, up to approximately 24 months | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Secondary | Extracranial Progression-free Survival (ePFS) in Both Cohorts | Defined as the time from the date of inclusion to the date of the first documented extracranial disease progression or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria). The local Investigator's assessments was used for analyses. Those patients who were alive and had not progressed at the last follow-up, date of progression was censored at the date of the last follow-up. Patients with no additional image test other than baseline were censored the day after inclusion. | | Posted | | Median | 95% Confidence Interval | months | | Throughout the study period, up to approximately 24 months | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Secondary | Intracranial Progression-free Rates | Proportion of patients free of intracranial progression assessed by modified RECIST at 6 months (week 24), 12 months (week 48) and 24-month (week 96) considering date of inclusion estimated through Kaplan-Meier method | | Posted | | Number | 95% Confidence Interval | Percentage of patients free of PD | | at 6 months (week 24), 12 months (week 48) and 24-month (week 96) | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Secondary | Overall Survival | Calculated as the time from date of inclusion to date of death due to any cause. | | Posted | | Median | 95% Confidence Interval | months | | Throughout the study period, up to approximately 24 months | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Secondary | Overall Survival Rates | Proportion of of patients alive at 6 months, 12 month and 24-month considering date of inclusion estimated using Kaplan-Meier. Patients alive at the moment of the analysis were censored on the date of their last follow-up. | | Posted | | Number | 95% Confidence Interval | Percentage of patients alive | | at 6 months, 12 month and 24-month | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Secondary | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Number of patients experiencing treatment related adverse events. These events were graded accrding to CTCAE, a scale that ranges from 0 (less intense; no event) to 5 (death) . Here we report the number of patients experiencing any grade toxicities and the number of patients experiencing high grade (grade 3-5) toxicities. | | Posted | | Count of Participants | | Participants | | Throughout the study period, up to approximately 24 months | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Secondary | Change on Quality of Life at Week 8 in Both Cohorts Based on the EORTC QLQ 30 Scale | The EORTC QLQ-C30 questionnaire is validated for cancer. It is composed of 30 questions or items that assess QoL. The questionnaire is structured in 5 functional scales physical functioning, daily activities, emotional functioning, cognitive functioning and social functioning), 3 symptom scales (fatigue, pain and nausea, vomiting), 1 global health status scale, and 6 independent items (dyspnea, insomnia, anorexia, constipation, diarrhea and economic impact). Values between 1 and 4 (1: not at all, 2: a little, 3: quite, 4: a lot) are assigned according to the patient's responses to the item, only in items 29 and 30 are they evaluated with a score of 1 to 7 (1: dreadful, 7: excellent). The scores obtained are standardized and a score between 0 and 100 is obtained, which determines the level of impact of the cancer on the patient on each of the scales. Higher values indicate better performance | Only patients who completed the quality of life questionnaires | Posted | | Median | Full Range | Score | | 8 weeks | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Secondary | Change on Quality of Life at Week 24 in Both Cohorts Based on the EORTC QLQ 30 Scale | The EORTC QLQ-C30 questionnaire is validated for cancer. It is composed of 30 questions or items that assess QoL. The questionnaire is structured in 5 functional scales physical functioning, daily activities, emotional functioning, cognitive functioning and social functioning), 3 symptom scales (fatigue, pain and nausea, vomiting), 1 global health status scale, and 6 independent items (dyspnea, insomnia, anorexia, constipation, diarrhea and economic impact). Values between 1 and 4 (1: not at all, 2: a little, 3: quite, 4: a lot) are assigned according to the patient's responses to the item, only in items 29 and 30 are they evaluated with a score of 1 to 7 (1: dreadful, 7: excellent). The scores obtained are standardized and a score between 0 and 100 is obtained, which determines the level of impact of the cancer on the patient on each of the scales. Higher values indicate better performance | Only patients who completed the quality of life questionnaires | Posted | | Median | Full Range | Score | | 24 weeks | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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| Secondary | Extracranial Progression-free Rates | Proportion of patients free of extracranial progression assessed by modified RECIST at 6 months (week 24), 12 months (week 48) and 24-month (week 96) considering date of inclusion estimated through Kaplan-Meier method | | Posted | | Number | 95% Confidence Interval | Percentage of patients free of PD | | at 6 months (week 24), 12 months (week 48) and 24-month (week 96) | | | | ID | Title | Description |
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| OG000 | COMBO450 | Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death. encorafenib: 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. binimetinib: Binimetinib 15mg (tablets) for a 45mg/12 hours for oral administration during 56 days and after local radiation treatment. Whole brain radiation therapy: 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. Radiosurgery/stereotactic radiosurgery: 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. |
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