Afatinib Treatment for Patients With EGFR Mutation Positive NSCLC Who Are Age 70 or Older

A Single Arm Phase IV Study of Afatinib in Elderly Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer Whose Tumors Have Epidermal Growth Factor Receptor (EGFR) Exon 19 Deletions or Exon 21(L858R) Substitution Mutations

Continuous treatment until progression or occurence of intolerable Adverse Event (AE) or end of trial. The end of trial is one year after the last patient has entered the study.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung; ErbB Receptors
• Intervention / Treatment: Drug: Afatinib

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85250
      • Mayo Clinic-Arizona
  • California
    • Anaheim, California, United States, 92801
      • Pacific Cancer Medical Center, Inc.
    • Duarte, California, United States, 91010
      • City of Hope
    • Fountain Valley, California, United States, 92708
      • Compassionate Care Research Group, Inc. at Compassionate Cancer Care Medical Group, Inc.
    • Los Angeles, California, United States, 90017
      • Los Angeles Hematology Oncology Medical Group
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Health D'Amour Center for Cancer Care
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • Pennsylvania
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Pathologically or cytologically confirmed NSCLC Stage IV Cancer (includes cytologically proven pleural effusion or pericardial effusion) or recurrent disease. Staging is based on American Joint Committee on Cancer (AJCC) Staging for NSCLC 7th edition (R12-4710)
• Evidence of common EGFR mutation (Del 19 and/or L858R)
• Age >= 70 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (R01-0787)
• Further inclusion criteria apply.

Exclusion criteria:

• Prior participation in an afatinib clinical study, even if not assigned to afatinib treatment
• Prior systemic therapy for metastatic or recurrent NSCLC.
• Concurrent investigational therapy or investigational therapy within 4 weeks of start of afatinib therapy

• Radiotherapy within 4 weeks prior to start of study treatment, except as follows:

  • Palliative radiation to target organs other than chest may be allowed up to 2 weeks prior to study treatment, or
  • Single dose palliative treatment for symptomatic metastasis outside above allowance to be discussed with sponsor prior to enrolling.
  • Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
  • Systemic chemotherapy, biological therapy, immunotherapy or investigational agents within 5 half-life of the drug or within four weeks prior to the start of afatinib treatment (if the half-life of the drug is unknown).
• Men, capable of fathering a child, who are unwilling to use adequate contraception prior to study entry, for the duration of study participation, and for at least 28 days after treatment has ended.
• Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afatinib; afatinib starting at 30 mg daily dose	Drug: Afatinib; afatinib starting at 30 mg daily dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting an Adverse Event (AE) Leading to Dose Reduction of Afatinib	On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).	On-treatment period + 28 days (residual effect period), up to 1057 + 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Event = Diarrhoea of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Higher	Percentage of participants with adverse event being diarrhoea of CTCAE grade 3 or higher. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).	On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
Percentage of Participants With Adverse Event = Rash/Acne (Grouped Term) of CTCAE Grade 3 or Higher	Percentage of participants with adverse event = rash/acne (grouped term) of CTCAE grade 3 or higher. MedDRA preferred terms that described AEs of similar nature were grouped together as "grouped term" to ensure that important events would not be underestimated. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).	On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
Percentage of Participants With Adverse Event = Stomatitis (Grouped Term) of CTCAE Grade 3 or Higher	Percentage of participants with adverse event = stomatitis (grouped term) of CTCAE grade 3 or higher. MedDRA preferred terms that described AEs of similar nature were grouped together as "grouped term" to ensure that important events would not be underestimated. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).	On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
Percentage of Participants With Adverse Event = Paronychia (Grouped Term) of CTCAE Grade 3 or Higher	Percentage of participants with adverse event = paronychia (grouped term) of CTCAE grade 3 or higher. MedDRA preferred terms that described AEs of similar nature were grouped together as "grouped term" to ensure that important events would not be underestimated. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent for study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria).	On-treatment period + 28 days (residual effect period), up to 1057 + 28 days
Time to First Dose Reduction of Afatinib Caused by Adverse Events	Time to first dose reduction of afatinib caused by adverse events is defined as time from the date of the first administration of afatinib to the date of first dose reduction of afatinib caused by adverse events. Participants without AEs leading to dose reduction were censored at date of last intake of afatinib. On-treatment period = First administration of afatinib until progression or intolerable adverse events or other reasons necessitating withdrawal (participant's withdrawal of consent from study treatment, participant diagnosed with interstitial lung disease, participant no longer able to receive study treatments, participant had a significant deviation from the protocol or eligibility criteria). The cumulative probability of no dose reduction at the respective time point is given by the Kaplan-Meier estimate at the respective time point based on time to first dose reduction of afatinib caused by adverse events.	On-treatment period, up to 1057 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2015
• Primary Completion (Actual): March 28, 2019
• Study Completion (Actual): April 25, 2019

Study Registration Dates

• First Submitted: July 17, 2015
• First Submitted That Met QC Criteria: July 31, 2015
• First Posted (Estimate): August 3, 2015

Study Record Updates

• Last Update Posted (Actual): March 30, 2020
• Last Update Submitted That Met QC Criteria: March 16, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Afatinib
• Other Study ID Numbers: 1200.209