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

March 27, 2019 updated by: Yonsei University
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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Afatinib plus Ruxolitinib combination (single arm)
Drug: Afatinib plus Ruxolitinib combination therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To set a recommended phase II dose (RP2D)
Time Frame: 36 days
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)
Time Frame: 1year
Adverse events (AEs) will be assessed according to NCI common toxicity criteria (CTC) version 4.03.
1year
Overall response rate (ORR)
Time Frame: 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)
1year
Progression free survival (PFS)
Time Frame: 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.
1year
Overall survival (OS)
Time Frame: 1year
OS will be defined as the start of the treatment to the date of death due to any cause.
1year
Pharmacodynamic biomarker
Time Frame: 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.
1year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yonsei University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 7, 2015

Primary Completion (ACTUAL)

November 9, 2017

Study Completion (ACTUAL)

November 9, 2017

Study Registration Dates

First Submitted

April 23, 2014

First Submitted That Met QC Criteria

May 20, 2014

First Posted (ESTIMATE)

May 23, 2014

Study Record Updates

Last Update Posted (ACTUAL)

March 29, 2019

Last Update Submitted That Met QC Criteria

March 27, 2019

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4-2013-0405

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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