Afatinib as Second-line Therapy for Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation

An Open Label, Single-arm Phase IV Study to Assess the Efficacy and Safety of Afatinib as Second-line Therapy for Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harbouring an EGFR Mutation (Del19 or L858R) Who Have Failed First-line Treatment With Platinum-based Chemotherapy

The objectives of this single-arm, open-label trial are to assess the efficacy and safety of afatinib as second line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring a common EGFR mutation who have failed first-line platinum-based chemotherapy and to demonstrate that the efficacy and safety are comparable to the results seen in previous trials.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21131
    • Clinical Research Center, Alexandria University Hospital
  • Cairo, Egypt, 11796
    • National Cancer Institute, Cairo University
  • Cairo, Egypt, 12311
    • Kasr Al Ainy Hospital
• Malaysia
  • Nilai, Malaysia, 71800
    • Nilai Medical Centre
• Philippines
  • Baguio City, Philippines, 2600
    • Baguio General Hospital and Medical Center
  • Taguig, Philippines, 1634
    • St. Luke's Medical Center
• Poland
  • Gdansk, Poland, 80-952
    • University Clinical Center, Gdansk
  • Szczecin-Zdunowo, Poland, 70-891
    • Specialist Hospital, Szczecin-Zdunowo
  • Warsaw, Poland, 02-781
    • Oncol Centre M Sklodowska-Curie, Dept of Lung & Chest Cancer
• Romania
  • Braila, Romania, 810303
    • Braila County Emergency Hospital, Medical Oncology
  • Bucharest, Romania, 022328
    • Institute of Oncology 'Prof. Dr. Alexandru Trestioreanu'
  • Craiova, Romania, 200347
    • Sf. Nectarie Oncology Center, Craiova
  • Iasi, Romania, 700483
    • Regional Oncology Institute of Iasi, Medical Oncology
• Serbia
  • Belgrade, Serbia, 11000
    • Institute for Oncol & Radiol of Serbia, Clinic f. Med. Onco.
  • Belgrade, Serbia, 11129
    • Clinical Center of Serbia
  • Kragujevac, Serbia, 34000
    • Clinical center Kragujevac
  • Sremska Kamenica, Serbia, 21204
    • Inst. for Pulm. Diseases of Vojvodine, Clinic f. Pulm. Oncol
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital
  • Bangkok, Thailand, 10310
    • Wattanosoth Hospital
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
2. Documented EGFR mutation (L858R and/or Deletion 19) with no other known EGFR mutation.
3. Measureable disease according to RECIST 1.1.
4. Radiologically confirmed progression or recurrence of disease during or following first line therapy with a platinum-based chemotherapy regimen.
5. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
6. Adequate organ function.

Exclusion criteria:

1. More than one line of prior therapy for disease.
2. Previously received less than 3 cycles of platinum-based chemotherapy due to toxicity and/or intolerance of treatment.
3. Previous treatment with any EGFR targeting Tyrosine Kinase Inhibitor (TKI) or antibody.
4. Known pre-existing interstitial lung disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afatinib; Afatinib tablet once daily until progression	Drug: Afatinib; Afatinib tablet once daily until progression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Tumour Response (Complete Response [CR], Partial Response [PR]) as Assessed by the Investigator According to the RECIST Version 1.1	As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions	Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) as Assessed by the Investigator According to RECIST 1.1.	Progression-free survival (PFS) is the time from treatment start to disease progression (or death if the patient died before progression). PFS as assessed based on investigator review according to the response evaluation criteria in solid tumours (RECIST) version 1.1.	Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
Disease Control (CR, PR, Stable Disease [SD]) as Assessed by the Investigator According to RECIST 1.1	As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.	Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2014
• Primary Completion (Actual): May 17, 2017
• Study Completion (Actual): June 13, 2017

Study Registration Dates

• First Submitted: August 4, 2014
• First Submitted That Met QC Criteria: August 4, 2014
• First Posted (Estimate): August 5, 2014

Study Record Updates

• Last Update Posted (Actual): December 17, 2018
• Last Update Submitted That Met QC Criteria: June 1, 2018
• Last Verified: June 1, 2018

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: 1200.217; 2014-001077-14 (EudraCT Number)