Phase I Study of the Combination of Afatinib and Ruxolitinib in Patients With Treatment-refractory Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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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.

Conditions
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NSCLC

Intervention / Treatment
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* Drug: Afatinib plus Ruxolitinib combination therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage 4 NSCLC patients disease progression after platinum doublet (all), EGFR TKI (if EGFR mutant), and crizotinib (if ALK positive) Men and women aged 20 years or older Recovery from previous drug-related toxicity: CTCAE 4.03 ≤ Grade 1 ECOG 0 or 1 able to orally take and retain drug have a measurable or unmeasurable lesion under RECIST 1.1 Criteria have proper hematological, renal, and hepatic functions intention to use an acceptable contraception able to read and understand the informed consent form Exclusion Criteria: previous chemotherapy, radiation therapy, immunotherapy, or other anticancer therapy within 14 days Clinically significant gastrointestinal disorder or malabsorption syndrome Acute digestive disorder major organ failure Significant cardiac disorders major operation of a main organ in 4 weeks Untreated symptomatic brain metastasis pregnant or nursing previously diagnosed Interstitial lung disease(ILD) previously treated with irreversible pan-HER inhibitor including Afatinib or Ruxolitinib previously experienced hypersensitivity to an ingredient of the study drug must receive CYP3A4 inducer or inhibitor persistently during the study period. HIV positive or active hepatitis threatening patient's safety is predicted

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afatinib plus Ruxolitinib combination (single arm)<br> | Drug: Afatinib plus Ruxolitinib combination therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To set a recommended phase II dose (RP2D) | We will set a recommended phase II dose (RP2D) using conventional 3+3 deisgn. | 36 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability (dose relating toxicity; DLT) | Adverse events (AEs) will be assessed according to NCI common toxicity criteria (CTC) version 4.03. | 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) | 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. | 1year | 
| Overall survival (OS) | OS will be defined as the start of the treatment to the date of death due to any cause. | 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. | 1year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Lung cancer, Head and neck squamous cell carcinoma, Afatinib, Ruxolitinib, EGFR, JAK, STAT