Afatinib in EGFR+NSCLC (Recurrent or Stage IV) - Patients With Poor Performance Status (ECOG 2 or 3)

Study Overview
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Brief Summary
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There is a medical need for improving treatment of poor performance status patients with EGFR driver mutations and documenting safety and tolerability of existing agents.

Official Title
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An Open-label, Single-arm Phase IV Study of Afatinib in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer Who Have Poor Performance Status and Whose Tumors Have the Common Epidermal Growth Factor Receptor (EGFR) Mutations, Exon 19 Deletions or Exon 21(L858R) Substitution Mutations

Conditions
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Carcinoma, Non-Small-Cell Lung, ErbB Receptors

Intervention / Treatment
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* Drug: Afatinib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Pathologically or cytologically confirmed NSCLC Stage IV Cancer (includes cytologically proven pleural effusion or pericardial effusion) or recurrent disease. The staging is based on American Joint Committee on Cancer (AJCC) Tumor Node Metastatic (TNM) classification of malignant tumors, 7th edition Evidence of common EGFR activating mutations (Del 19 and/or L858R) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 or 3 Adequate organ function, defined as all of the following: Absolute neutrophil count (ANC) > 1500 / mm3 Platelet count >75,000 / mm3. Baseline creatinine of < or = 1.5 g/dl or, if > 1.5, an estimated creatinine clearance of > 45 ml/min Total Bilirubin < 1.5 times upper limit of institutional normal (ULN) Aspartate amino transferase (AST) or alanine amino transferase (ALT) < three times ULN (if related to liver metastases < five times ULN) Recovery from any previous therapy related toxicity to< or = Grade 1 at study entry (except for stable sensory neuropathy < or =Grade 2 and alopecia) Life expectancy of at least three months Written informed consent that is consistent with International Council on Harmonization- Good Clinical Practice (ICH-GCP) guidelines Age 18 or older Exclusion criteria: Prior participation in an afatinib clinical study, even if not assigned to afatinib treatment Prior systemic therapy for metastatic or recurrent NSCLC including prior treatment with EGFR targeting small molecules or antibodies. Note: radiotherapy alone and adjuvant/neoadjuvant treatment is not counted as a line of therapy. 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: i.) Palliative radiation to target organs other than chest may be allowed up to 2 weeks prior to study treatment, or ii.) Single dose palliative treatment (e.g Stereotactic Radio Surgery(SRS) or Stereotactic Body Radiation Therapy) (SBRT) 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 Women of child-bearing potential (WOCBP) and men who are able to father a child, or use adequate contraception prior to study entry, for the duration of study participation and for at least 28 days after treatment has ended. Presence of an active infection or with a fever > 38.5 C within 3 days of the first scheduled day of dosing Known hypersensitivity to afatinib or the excipients of afatinib Known pre-existing interstitial lung disease Pathologically documented meningeal carcinomatosis (i.e. cytology (+) lumbar puncture ; radiology reports alone raising this as a possibility, in the absence of true symptomatology, would not constitute an exclusion) Presence of brain or subdural metastases, unless local therapy has been completed and use of corticosteroids has been discontinued or the dose has been stable for at least 4 weeks before starting study treatment. Any symptoms attributed to brain metastases must be stable for at least 4 weeks before starting study treatment (Pts post SRS can be enrolled earlier as long as their symptoms are stable or improved and they are off steroids) 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 2 years and is considered to be cured History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3 or 4 unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to treatment with afatinib. Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhoea, malabsorption) Known or suspected active hepatitis B (Hep B) infection (defined as presence of HepB (surface Antigen) sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the safety and efficacy of the test drug Treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afatinib<br> | Drug: Afatinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Occurrence of Adverse Events (AEs) Leading to Dose Reduction of Afatinib | Percentage of patients with occurrence of Adverse Events (AEs) leading to dose reduction of afatinib. | Up to 98 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Occurrence of CTCAE Grade 3 or Higher Diarrhoea, Rash/Acne+, Stomatitis+ and Paronychia+ (+ Represents Grouped Term) | Percentage of patients with occurrence of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher diarrhoea, rash/acne+, stomatitis+ and paronychia+ (+ represents grouped term). | Up to 98 days | 
| Time to First Dose Reduction of Afatinib Caused by Adverse Events (AEs) | Time to first dose reduction of afatinib caused by Adverse Events (AEs) defined as time from the date of the first administration of afatinib to the first dose reduction of afatinib caused by AEs. | Up to 98 days |