Afatinib in EGFR+NSCLC (Recurrent or Stage IV) - Patients With Poor Performance Status (ECOG 2 or 3)
Condition: Carcinoma, Non-Small-Cell Lung; ErbB Receptors
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Afatinib
Intervention MeSH terms: Afatinib
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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