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

Phase 1

Completed

• Conditions: NSCLC
• Interventions: Drug: Afatinib plus Ruxolitinib combination therapy

• Registration Number: NCT02145637
• Lead Sponsor: Yonsei University

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2014-04-23
• Study First Submitted QC: 2014-05-20
• Study First Posted: 2014-05-23
• Study Start: 2015-05-07
• Primary Completion: 2017-11-09
• Study Completion: 2017-11-09
• Status Verified: 2018-03
• Last Update Submitted: 2019-03-27
• Last Update Posted: 2019-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Afatinib plus Ruxolitinib combination (single arm)	Afatinib plus Ruxolitinib combination therapy	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 survival (OS)	1year	OS will be defined as the start of the treatment to the date of death due to any cause.
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.
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.
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)