FOLFOX in Combination with Binimetinib as 2nd Line Therapy for Patients with Advanced Biliary Tract Cancers with MAPK Pathway Alterations: A ComboMATCH Treatment Trial
Categories (click each to see list of all clinical trials associated with that category): GI (ONC)
Current Status: Open
Phase: II (Cancer Control)
Principal Investigator: Krishnan, Mridula
Contact Information:
Jessica Delaney
jessdelaney@unmc.edu
Eligibility: https://clinicaltrials.gov/study/NCT05564403?term=NCT05564403&rank=1&tab=table#recruitment-information
Summary
2.1 Primary objective
To determine whether binimetinib and mFOLFOX6 combination therapy improves overall survival (OS) compared to mFOLFOX6 alone in patients with advanced/recurrent BTC and with alterations in RAS/RAF/MEK/ERK pathway, who have progressed on one prior line of therapy.
2.2 Secondary objective(s)
2.2.1 To determine whether binimetinib and mFOLFOX6 combination therapy improves objective response rate (ORR) compared to FOLFOX alone.
2.2.2 To determine if clinical outcomes including progression free survival (PFS), duration of response (DOR), and disease control rate (DCR) are improved with combination treatment of binimetinib and mFOLFOX6 compared to FOLFOX alone in patients with advanced/recurrent BTC and with alterations in RAS/RAF/MEK/ERK pathway who have progression on one prior line of therapy.
2.2.3 Toxicity and tolerability will be evaluated within and between the two treatment arms, where frequency, type, and severity of adverse events will be assessed per the NCI CTCAE v5.0.
2.2.4 Collect tissue and provide it to the ComboMATCH Registration Protocol to assess concordance between the diagnostic tumor mutation profile generated by the Designated Laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment ctDNA mutation profile from plasma, as described in ComboMATCH Registration Protocol. For this treatment substudy, the outcome objective will be to report the proportion of cases providing sufficient tissue for that integrated scientific activity in the ComboMATCH Registration Protocol.
2.3 Exploratory objectives
2.3.1 Generate a prognostic model of MAPK mutations for this patient population using clinical, laboratory and molecular features of their disease and clinical outcome to validate on future samples.
2.3.2 Correlation of outcome with albumin.
2.3.3 Assess the correlation between the presence of MAPK pathway mutations and activity of addition of binimetinib therapy to standard 2nd line chemotherapy.
2.3.4 Conduct whole-exome sequencing and RNA-sequencing at baseline, and on optional biopsy upon progression to assess determinants of response and resistance.
2.3.5 Explore changes in plasma MAPK mutations allelic burden and other molecular findings at baseline and upon progression using ctDNA and correlate changes with clinical activity, disease course as well as response/resistance to therapy.
2.3.6 Evaluate if our machine learning algorithm for RAS/RAF/MEK/ERK pathway mutations correlates with detection of mutations as well as prediction of outcomes from samples obtained in this study.