Phase 2 Trial of Afatinib Plus Prednisone for Advanced Squamous NSCLC

• ClinicalTrials.gov Identifier: NCT04497584
• Recruitment Status: Recruiting
• First Posted: August 4, 2020
• Last Update Posted: June 30, 2022
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Sheena Bhalla, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

To determine the efficacy of combined afatinib and prednisone in previously treated advanced squamous NSCLC

Condition or disease	Intervention/treatment	Phase
Advanced Squamous Non Small Cell Lung Cancer	Drug: Afatinib + Prednisone	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Afatinib 40 mg PO daily Prednisone 40 mg PO daily (starting 7 days after afatinib)
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Investigator-sponsored Phase 2 Trial of Afatinib Plus Prednisone for Advanced Squamous Non-small Cell Lung Cancer
• Actual Study Start Date: August 4, 2021
• Estimated Primary Completion Date: September 1, 2023
• Estimated Study Completion Date: September 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Afatinib + Prednisone; Afatinib 40 mg PO daily Prednisone 40 mg PO daily starting 7 days after Afatinib	Drug: Afatinib + Prednisone; 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Response rate of combined afatinib and prednisone in previously treated NSCLC [ Time Frame: From date of enrollment to date of documented progression or death from any cause, whichever came first, assessed up to 60 months ]
   Measure response rate by evaluation of target lesions by measuring disease.
2. Overall survival of combined afatinib and prednisone in previously treated NSCLC [ Time Frame: From date of enrollment to date of documented progression or death from any cause, whichever came first, assessed up to 60 months ]
   Measure Overall Survival, as the time from the date of initiation of study treatment until death of any cause.
3. Safety of combined afatinib and prednisone in previously treated NSCLC [ Time Frame: From date of enrollment to date of documented progression or death from any cause, whichever came first, assessed up to 60 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Sheena Bhalla, MD; 214-648-4180; sheena.bhalla@utsouthwestern.edu

Contact: Jeffery Wilson, BS; 214-648-7097; Jeffery.Wilson@UTSouthwestern.edu

Locations

United States, Texas

UT Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

Contact: Jeffery Wilson, BS 214-648-7097 Jeffery.Wilson@UTSouthwestern.edu

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: Sheena Bhalla, MD; UT Southwestern Medical Center

More Information

• Responsible Party: Sheena Bhalla, Assistant Professor of Medicine, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT04497584
• Other Study ID Numbers: STU-2020-0509
• First Posted: August 4, 2020
• Last Update Posted: June 30, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Prednisone; Afatinib; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action