Phase 2 Trial of Afatinib Plus Prednisone for Advanced Squamous NSCLC

Study Overview
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Brief Summary
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To determine the efficacy of combined afatinib and prednisone in previously treated advanced squamous NSCLC

Detailed Description
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This two-stage phase 2 study will determine the safety, tolerability, recommended phase 2 dose/maximum tolerated dose, preliminary efficacy and predictive/pharmacodynamic biomarkers of combined EGFR inhibition (afatinib) and TNF inhibition (prednisone) in previously treated NSCLC.

Official Title
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An Investigator-sponsored Phase 2 Trial of Afatinib Plus Prednisone for Advanced Squamous Non-small Cell Lung Cancer

Conditions
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Advanced Squamous Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Afatinib + Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure. Previously treated (up to three prior lines of therapy), histologically proven advanced squamous NSCLC. No prior treatment with EGFR inhibitors, IMIDs (eg, thalidomide, lenalidomide), or anti-TNF antibodies. No treatment with systemic glucocorticoids within 3 weeks of initiation of study therapy (topical and inhaled glucocorticoids are permitted). Age ≥ 18 years. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate organ and marrow function as defined below: absolute neutrophil count ≥ 1,000/μL platelets ≥ 50,000/μl total bilirubin within normal institutional limits AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal CrCl ≥ 45 ml/min For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment. Adequate archival tissue (5-10 slides) for correlative studies. Subject must have measurable disease per RECIST 1.1 Exclusion Criteria: Chemotherapy, radiotherapy, or other cancer therapy within two weeks prior to starting study treatment. Subjects must have recovered from prior treatment-related to toxicities to grade 1 or baseline (excluding alopecia and clinically stable toxicities requiring ongoing medical management, such as hypothyroidism from prior immune checkpoint inhibitor treatment). Subjects may not be receiving any other investigational agents for the treatment of the cancer under study. Symptomatic brain metastases or brain metastases requiring escalating doses of corticosteroids History of hypersensitivity or allergic reactions attributed to afatinib or prednisone. Uncontrolled intercurrent illness including but not limited to poorly controlled diabetes (which may worsen in setting of chronic prednisone therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Afatinib 40 mg PO daily Prednisone 40 mg PO daily (starting 7 days after afatinib)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afatinib + Prednisone<br>Afatinib 40 mg PO daily Prednisone 40 mg PO daily starting 7 days after Afatinib | Drug: Afatinib + Prednisone<br>* Afatinib (40mg) will be taken by mouth daily starting on Cycle 1, Day -7. Prednisone (40mg) will be taken by mouth daily starting on Cycle 1, Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival of combined afatinib and prednisone in previously treated NSCLC | Measure progression-free survival rate. | From date of enrollment to date of documented progression or death from any cause, whichever came first, assessed up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of combined afatinib and prednisone in previously treated NSCLC | Measure response rate by evaluation of target lesions by measuring disease. | From date of enrollment to date of documented progression or death from any cause, whichever came first, assessed up to 60 months | 
| Overall survival of combined afatinib and prednisone in previously treated NSCLC | Measure Overall Survival, as the time from the date of initiation of study treatment until death of any cause. | From date of enrollment to date of documented progression or death from any cause, whichever came first, assessed up to 60 months | 
| Safety of combined afatinib and prednisone in previously treated NSCLC | Measure risk to study participants by completing blood test and assessing according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0. | From date of enrollment to date of documented progression or death from any cause, whichever came first, assessed up to 60 months |