Afatinib in NSCLC With HER2 Mutation
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: afatinib; paclitaxel
Intervention MeSH terms: Paclitaxel; Afatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      to investigate effectiveness and safety of afatinib in the advanced NSCLC patients with HER2
      mutations, previously treated with 1 or 2 chemotherapy regimens
    

Eligibility criteria:

        Inclusion criteria:

          -  Patients with Histologically or cytologically confirmed diagnosis of stage IIIb/IV
             NSCLC (AJCC 7.0), who had failed one or two systemic chemotherapy regimens, one of
             which must be platinum-based .

          -  Tumor tissue with HER2 mutations as confirmed by AmoyDx® HER2 Mutation Detection Kit

          -  Patients with at least one measurable tumor lesion that can accurately be measured by
             CT scan or MRI according to RECIST 1.1

          -  Age>=18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1

          -  Adequate organ function

          -  Recovered from any previous therapy related toxicity to <=Grade 1 at study entry
             (except for stable sensory neuropathy <=Grade 2 and alopecia)

          -  Written informed consents that is consistent with International Conference on
             Harmonisation (ICH) - Good Clinical Practice (GCP) and local GCP guidelines Inclusion
             criterion for Part B

          -  Adequate organ function, as inclusion criteria No.6

          -  ECOG performance score 0~2

          -  More than 12 weeks clinical benefit (PR, Complete Response (CR), SD) in part A Further
             inclusion criteria apply

        Exclusion criteria:

          -  Prior treatment with Epidermal Growth Factor Receptor (EGFR) or HER2 targeting small
             molecules or antibodies.

          -  Any chemo-, or immune anticancer therapy within 4 weeks prior to start of study
             treatment, Hormonal treatment within 2 weeks prior to start of study treatment,
             Radiotherapy within 4 weeks prior to start of treatment, except as follows:

             i.) Palliative radiation to target organs other than chest may be allowed up to 2
             weeks prior to enter, and ii.) 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

          -  Known hypersensitivity to afatinib or the excipients of any of the trial drugs

          -  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 randomisation.

          -  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 efficacy and safety of the test drug.

          -  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.

          -  Requiring treatment with any of the prohibited concomitant medications

          -  Known pre-existing interstitial lung disease.

          -  Any history or presence of poorly controlled gastrointestinal disorders that could
             affect the absorption of the study drug.

          -  Active hepatitis B infection and/or active hepatitis C infection and/or known HIV
             carrier.

          -  Leptomeningeal carcinomatosis.

          -  Symptomatic brain metastases; To be eligible patients must be asymptomatic from brain
             metastases at least 4 weeks without requirement for steroids or anti-epileptic
             therapy.

          -  Women of child-bearing potential (WOCBP) and men who are able to father a child,
             unwilling to be abstinent or use highly effective methods of birth control for the
             duration of study participation and for at least 2 weeks after treatment has ended.

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial
             Exclusion criterion for Part B Any known contraindication for paclitaxel treatment.
             Not able to tolerate lowest dose of afatinib. Peripheral polyneuropathy >Grade 2
             Further exclusion criteria apply