A Phase 2 interventional study of Encorafenib + Binimetinib in Melanoma Stage III and In-Transit Metastasis of Cutaneous Melanoma, sponsored by Leiden University Medical Center. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-03-14.
Sponsored by Leiden University Medical Center · Phase 2, Interventional, and Treatment
Phase 2 open-label single arm intervention study administering encorafenib/binimetinib in neo-adjuvant setting followed by surgery and subsequent adjuvant encorafenib/binimetinib in in-transit melanoma patients without lymph node and distant metastases.
Phase 2 open-label single arm intervention study administering encorafenib/binimetinib in neo-adjuvant setting followed by surgery and subsequent adjuvant encorafenib/binimetinib in patients diagnosed solely with in-transit metastatic melanoma.
Primary objective is to determine the efficacy of neo-adjuvant encorafenib/binimetinib as measured by pathological response rate (partial-, complete- and no response). In the biopsy at week 0 the viability will be judged and will be graded according to the amount of tumor necrosis: >50% tumor necrosis with \<50% viable tumor cells, \<50% necrosis with >50% viable tumor cells and 100% necrosis without viable tumor cells. Partial response is defined as a decrease of at least 50% of the viable tumor cells and complete response as 100% decrease of tumor cells, whereas no response is defined as more than 50% of viable tumor cells present.
Secondary objectives are to assess efficacy of adjuvant BRAF/MEK inhibition, measured as local recurrence free survival (LRFS), distant metastases-free survival (DFMS), recurrence free survival (local and/or distant recurrence, RFS) and overall survival (OS). Additionally, the toxicity of the administered regimen will be assessed by analyzing the frequency- and type of adverse events, and occurrences of therapy interruption, dose reduction and or therapy cessation. Moreover, an exploration of drug measurements and ctDNA in blood and additional research of biopsies / resections will be done.
3,005 studies on the registry are indexed under Melanoma; 519 are open to participants now.
This study's planned enrollment of 28 is below the median of 38 across 2,350 interventional studies indexed under Melanoma.
Browse Melanoma studies →Leiden University Medical Center is the lead sponsor of 326 studies on the registry; 106 are open to participants now.
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Exclusion Criteria:
Neo adjuvant BRAF/MEK inhibition (encorafenib/binimetinib). Patients receive encorafenib 450 mg once daily for a period of 8 weeks. Patients receive 45 mg binimetinib twice daily for a period of 8 weeks. After the neo-adjuvant therapie, patients will receive encorafenib 450 mg once daily fand binimetinib 45mg twice daily for 44 weeks.
Drug: Encorafenib + Binimetinib
In the open label phase II study, the combination of BRAF/MEK inhibition with encorafenib/binimetinib in the neo-adjuvant setting will be investigated. Furthermore, efficacy of adjuvant BRAF/MEK inhibition with encorafenib/binimetinib, for 44 weeks will be evaluated.
Efficacy of neo-adjuvant encorafenib/binimetinib
Primary outcome is to determine the efficacy of neo-adjuvant eEncorafenib/bBinimetinib as measured by pathological response rate (partial-, complete- and no response). In the biopsy at week 0 the viability will be judged and will be graded according to the amount of tumor necrosis: \>50% tumor necrosis with \<50% viable tumor cells, \<50% necrosis with \>50% viable tumor cells and 100% necrosis without viable tumor cells. Partial response is defined as a decrease of at least 50% of the viable tumor cells, and complete response is defined as more than 90% a decrease of more than 90% of the tumor cells, whereas no response is defined as more than 50% of viable tumor cells present.
Time frame: 8 weeks
Evaluate efficacy of treatment related toxicity
analyzing the frequency- and type of adverse events, and occurrences of therapy interruption, dose reduction and or therapycessation. Adverse events severity will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0. Adverse events associated with BRAF/MEK inhibition will be termed as treatment related or potentially treatment related, adverse events which are not known class effects of BRAF/MEK inhibitors will be described as adverse events not treatment related. Adverse event assessment will take place from therapy initiation up to completion of adjuvant treatment (week 44) and 30 das after.
Time frame: 52 weeks
Efficacy of adjuvant encorafenib/binimetinib - local recurrece free survival (LRFS)
To assess efficacy of adjuvant BRAF/MEK inhibition by analyzing the surgical site clinically (bimonthly) and radiologically (every 4 months) during the adjuvant treatment. Local disease recurrence is defined as pathologically confirmed metastasic melanoma in scar tissue and or recurrence of melanoma within 2cm of the surgical scar of primary melanoma of the previously removed melanoma. Local disease recurrence will be measured from start of adjuvant therapy up to disease recurrence confirmation.
Time frame: 44 weeks
Efficacy of adjuvant encorafeninb/binimetinib - distant metastases-free survival (DFMS)
To assess efficacy of adjuvant BRAF/MEK inhibition by analyzing the surgical site clinically (bimonthly) and radiologically (every 4 months) during the adjuvant treatment. Distant metastases free survival (DFMS) is defined as the moment of pathologically and or radiologically disease confirmation. Distant metastatic disease includes, distant lymph nodes and organs. Distant metastatic free survival will be calculated using the start of therapy up to the moment of distant metastatic disease confirmation or last follow-up moment.
Time frame: 44 weeks
Efficacy of adjuvant encorafeninb/binimetinib - overall survival
To assess efficacy of adjuvant BRAF/MEK inhibition by analyzing the surgical site clinically (bimonthly) and radiologically (every 4 months) during the adjuvant treatment. Overall survival is defined as the moment of primary melanoma up to decease.
Time frame: 44 weeks
Efficacy of adjuvant encorafeninb/binimetinib - treatment related survival
To assess efficacy of adjuvant BRAF/MEK inhibition by analyzing the surgical site clinically (bimonthly) and radiologically (every 4 months) during the adjuvant treatment. The moment of start of adjuvant therapy up to decease or last follow-up moment.
Time frame: 44 weeks
Plan to share: No
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Leiden University Medical Center