NSCLC
Conditions
Keywords
Cancer, Lung cancer, Head and neck squamous cell carcinoma, Afatinib, Ruxolitinib, EGFR, JAK, STAT
Brief summary
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.
Interventions
DRUGAfatinib plus Ruxolitinib combination therapy
Sponsors
Yonsei University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Stage 4 NSCLC patients 2. disease progression after platinum doublet (all), EGFR TKI (if EGFR mutant), and crizotinib (if ALK positive) 3. Men and women aged 20 years or older 4. Recovery from previous drug-related toxicity: CTCAE 4.03 ≤ Grade 1 5. ECOG 0 or 1 6. able to orally take and retain drug 7. have a measurable or unmeasurable lesion under RECIST 1.1 Criteria 8. have proper hematological, renal, and hepatic functions 9. intention to use an acceptable contraception 10. able to read and understand the informed consent form
Exclusion criteria
1. previous chemotherapy, radiation therapy, immunotherapy, or other anticancer therapy within 14 days 2. Clinically significant gastrointestinal disorder or malabsorption syndrome 3. Acute digestive disorder 4. major organ failure 5. Significant cardiac disorders 6. major operation of a main organ in 4 weeks 7. Untreated symptomatic brain metastasis 8. pregnant or nursing 9. previously diagnosed Interstitial lung disease(ILD) 10. previously treated with irreversible pan-HER inhibitor including Afatinib or Ruxolitinib 11. previously experienced hypersensitivity to an ingredient of the study drug 12. must receive CYP3A4 inducer or inhibitor persistently during the study period. 13. HIV positive or active hepatitis 14. threatening patient's safety is predicted
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To set a recommended phase II dose (RP2D) | 36 days | We will set a recommended phase II dose (RP2D) using conventional 3+3 deisgn. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability (dose relating toxicity; DLT) | 1year | Adverse events (AEs) will be assessed according to NCI common toxicity criteria (CTC) version 4.03. |
| Overall response rate (ORR) | 1year | 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) |
| Progression free survival (PFS) | 1year | 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. |
| Overall survival (OS) | 1year | OS will be defined as the start of the treatment to the date of death due to any cause. |
| Pharmacodynamic biomarker | 1year | 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. |
Outcome results
None listed