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

NSCLC Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02145637
• Other study ID #: 4-2013-0405
• Status: Completed
• Phase: Phase 1
• Start date: May 7, 2015
• Est. completion date: November 9, 2017

Study information

• Verified date: March 2018
• Source: Yonsei University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 9, 2017
• Est. primary completion date: November 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• NSCLC

Intervention

Drug:
• Afatinib plus Ruxolitinib combination therapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Outcome

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