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

NCT02145637 | Completed Phase 1 DMC

• 1 other identifier: 4-2013-0405
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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.

Conditions

NSCLC

Keywords

Cancer, Lung cancer, Head and neck squamous cell carcinoma, Afatinib, Ruxolitinib, EGFR, JAK, STAT

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Safety and tolerability (dose relating toxicity; DLT)

  1year

• Overall response rate (ORR)

  1year

• Progression free survival (PFS)

  1year

• Overall survival (OS)

  1year

• Pharmacodynamic biomarker

  1year

Study Arms (1)

Afatinib plus Ruxolitinib combination (single arm)

EXPERIMENTAL

Drug: Afatinib plus Ruxolitinib combination therapy

Interventions

Afatinib plus Ruxolitinib combination therapy DRUG

Afatinib plus Ruxolitinib combination (single arm)

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yonsei University: lead

Related Publications (1)

• Park JS, Hong MH, Chun YJ, Kim HR, Cho BC. A phase Ib study of the combination of afatinib and ruxolitinib in EGFR mutant NSCLC with progression on EGFR-TKIs. Lung Cancer. 2019 Aug;134:46-51. doi: 10.1016/j.lungcan.2019.05.030. Epub 2019 May 28.

  PMID: 31319994 DERIVED

MeSH Terms

Conditions

Neoplasms; Lung Neoplasms

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2014
• First Posted: May 23, 2014
• Study Start: May 7, 2015
• Primary Completion: November 9, 2017
• Study Completion: November 9, 2017
• Last Updated: March 29, 2019

Record last verified: 2018-03