Afatinib in Patients With Non Small Cell Lung Cancer (NSCLC) With Epidermal Growth Factor Receptor (EGFR) Mutations

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

An Open Label Trial of Afatinib in Treatment-naive or Chemotherapy Pre-treated Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) Harboring EGFR Mutation(s)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02044380
• Other study ID #: 1200.48
• Status: Completed
• Phase: Phase 3
• First received: January 22, 2014
• Last updated: March 1, 2016
• Start date: March 2014
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The main aim of this study is to evaluate the safety and tolerability of afatinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring Epidermal Growth Factor Receptor (EGFR) mutation(s) and have never been treated with an EGFR-Tyrosine Kinase Inhibitor (TKI)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC)

2. Epidermal Growth Factor Receptor (EGFR) mutation-positive results per the institution's testing methodology

3. Male or female patients age >=18 years

4. Adequate organ function, defined as all of the following:

1. Absolute neutrophil count (ANC) >1500/mm3

2. Platelet count>75,000/mm3

3. Serum creatinine<1.5 times of the upper limit of (institutional) normal and/or creatinine clearance (measured or calculated)>45ml/min

4. Total bilirubin <1.5 times upper limit of (institutional) normal

5. Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) < three times the upper limit of (institutional) normal (if related to liver metastases < five times ULN)

5. Eastern Cooperative Oncology Group (ECOG) score between 0-2

6. Written informed consent by patient or guardian prior to admission into the trial that is consistent with International Conference on Harmonization (ICH)- Good Clinical Practice (GCP) guidelines and local law

7. Recovery from any previous therapy related toxicity to <=CTCAE Grade 1 at study entry (except for stable sensory neuropathy <=CTCAE Grade 2 and alopecia)

Exclusion criteria:

1. Prior treatment with an EGFR tyrosine kinase inhibitor (TKI)

2. Hormonal anti-cancer treatment within 2 weeks prior to start of trial treatment (continued use of anti-androgens and/or gonadorelin analogues for treatment of prostate cancer permitted)

3. Radiotherapy within 28 days prior to drug administration, except as follows:

1. Palliative radiation to organs other than chest may be allowed up to 2 weeks prior to drug administration, and

2. Single dose palliative treatment for symptomatic metastases outside above allowance to be discussed with sponsor prior to enrolling

4. Major surgery within 4 weeks before starting trial treatment or scheduled for surgery during the projected course of the trial

5. Known hypersensitivity to afatinib or any of its excipients

6. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to starting trial treatment

7. Women of Child-Bearing Potential (WOCBP) and men who are able to father a child, unwilling to use adequate contraception prior to trial entry, for the duration of trial participation and for at least 2 weeks after treatment has ended

8. Childbearing potential who:

1. are nursing or

2. are pregnant or

3. are not using an acceptable method of birth control, or do not plan to continue using this method throughout the trial and/or do not agree to submit to pregnancy testing required by this protocol

9. Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patients ability to comply with the trial or interfere with the evaluation of safety for the trial drug

10. Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured

11. Requiring treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation

12. Known pre-existing interstitial lung disease

13. Presence of poorly controlled gastrointestinal disorders that could affect the absorption of the trial drug (e.g. Crohn¿s disease, ulcerative colitis, malabsorption, or CTC grade =2 diarrhea of any aetiology) based on investigator assessment

14. Active hepatitis B infection (defined as presence of Hepatitis B (HepB) sAg and/or HepB DNA), active Hepatitis C (HEP C) infection (defined as presence of Hep C RNA) and/or known Human Immunodeficiency Virus (HIV) carrier

15. Meningeal carcinomatosis

16. Symptomatic brain metastases (patients with asymptomatic brain metastases, who were previously treated, are eligible provided they have had Stable Disease (SD) for at least 4 weeks on stable doses of corticosteroid)

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Afatinib
40, 30, or 20mg tablets taken once daily, dosage depending on tolerability

Locations

Country	Name	City	State
Canada	1200.48.00003 Boehringer Ingelheim Investigational Site	Barrie	Ontario
Canada	1200.48.00009 Boehringer Ingelheim Investigational Site	London	Ontario
Canada	1200.48.00008 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1200.48.00007 Boehringer Ingelheim Investigational Site	Newmarket	Ontario
Canada	1200.48.00004 Boehringer Ingelheim Investigational Site	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of adverse events according to Common Terminology Criteria (CTCAE Version 3).		89 weeks	No