ADAM-Afatinib Diarrhea Assessment and Management
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung; Diarrhea
Intervention: afatinib; loperamide
Intervention description: Daily treatment starting 40 mg per day; Follow cohort assignment and diarrhea management guidelines
Intervention MeSH terms: Afatinib; Loperamide; Antidiarrheals
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a non-randomized, open label, two-cohort, multi-institutional study to evaluate the
      use of diarrheal management tools intended to facilitate timely intervention and treatment
      modifications due to afatinib treatment-related diarrhea in patients with EGFR
      mutations-positive adenocarcinoma of the lung. Patients in Cohort 1 will follow diarrhea
      management. Patients in Cohort 2 will receive prophylactic loperamide starting the fist day
      of afatinib treatment.
    

Eligibility criteria:

        Inclusion criteria:

          1. Pathologically confirmed diagnosis of Stage IIIB or Stage IV adenocarcinoma of the
             lung, with EGFR mutations-positive status, who are not eligible to receive surgery or
             chemoradiotherapy. Patients with mixed histology are eligible if adenocarcinoma is the
             predominant histology, and is a suitable candidate for EGFR-TKI monotherapy, in the
             opinion of the investigator.

          2. Patients must have Epidermal Growth Factor Receptor (EGFR) mutation-positive status
             according to the institutional standard of care.

          3. Patient received no more than one (1) prior chemotherapy for locally advanced or
             metastatic adenocarcinoma of the lung.

          4. Male or female patients Age 18 years and older.

          5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

          6. Adequate organ function, defined as all of the following:

               -  Left Ventricular Ejection Fraction (LVEF) of above 50% or within institution
                  normal values

               -  Absolute neutrophil count (ANC) above 1500 / mm3.

               -  Platelet count above 75,000 / mm3.

               -  Estimated creatinine clearance more than 45ml / min.

               -  Total Bilirubin less than 1.5 times upper limit of (institutional/central) normal

               -  Aspartate amino transferase (AST) or alanine amino transferase (ALT) less than
                  three times the upper limit of (institutional/central) normal (ULN) (if related
                  to liver metastases less than five times ULN).

          7. Recovered from any previous therapy related toxicity to Grade 0 or 1 at study entry

          8. Able and willing to follow diarrhea management guidelines provided under this study
             and to complete Diarrhea Management Worksheet as instructed.

        Exclusion criteria:

          1. Chemotherapy, biological therapy or investigational agents within four weeks prior to
             the start of study treatment.

          2. Prior treatment with EGFR directed small molecules or antibodies.

          3. Hormonal treatment within 2 weeks prior to start of study treatment (continued use of
             anti-androgens and/or gonadorelin analogues for treatment of prostate cancer
             permitted).

          4. Major surgery within 4 weeks before starting study treatment or scheduled for surgery
             during the projected course of the study.

          5. Known hypersensitivity to afatinib or the excipients of any of the trial drugs.

          6. History or presence of clinically relevant cardiovascular abnormalities.

          7. 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.

          8. Previous or concomitant invasive malignancies at other sites.

          9. Known pre-existing interstitial lung disease (ILD).

         10. Any history or presence of poorly controlled gastrointestinal disorders that could
             affect the absorption of the study drug.

        14. Active hepatitis B infection, active hepatitis C infection and/or known HIV carrier,
        who are determined by the investigator as not a suitable candidate to receive EGFR-TKI
        treatment.

        15. Patients with meningeal carcinomatosis. 16. Patients with brain or subdural metastases.