This phase Ib study will investigate dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of afatinib and ruxolitinib combination therapy, based on the preclinical data that inhibition of IL-6R/JAK1 signal transmission pathway will increase sensitivity to afatinib.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
To set a recommended phase II dose (RP2D)
We will set a recommended phase II dose (RP2D) using conventional 3+3 deisgn.
Time frame: 36 days
Safety and tolerability (dose relating toxicity; DLT)
Adverse events (AEs) will be assessed according to NCI common toxicity criteria (CTC) version 4.03.
Time frame: 1year
Overall response rate (ORR)
Response and progression will be evaluated in this study using modified international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
Time frame: 1year
Progression free survival (PFS)
PFS will be defined as the start of the treatment to the first occurrence of progression, relapse, or death from any cause as assessed by the investigator.
Time frame: 1year
Overall survival (OS)
OS will be defined as the start of the treatment to the date of death due to any cause.
Time frame: 1year
Pharmacodynamic biomarker
The biomarkers marker related with EGFR and JAK/STAT pathway as well as gene analysis, using peripheral blood mononuclear cell(PBMC), circulating tumor cell (CTC) and skin and tumor tissue sample will be analyzed.
Time frame: 1year
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