Tetracycline as a Prophylaxis for Rash in Patients With NSCLC Receiving Treatment With BIBW2992 (Afatinib)
Condition: Skin Rash; Lung Cancer
MeSH terms: Exanthema
Intervention: Tetracycline
Intervention description: The experimental group will receive tetracycline 250mg every 12 hours for 1 month the same day at initiation of BIBW2992 whereas the non-intervention group will recieve general dermatological recomendations while on treatment with BIBW2992.
Intervention MeSH terms: Tetracycline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Enrollment: 107.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung cancer; BIBW 2992; Skin Rash; Tetracycline; Afatinib

Summary:

      1. Advanced NSCLC has a poor prognosis and the positive impact of chemotherapy is limited
           by the development of intrinsic and acquired resistance.

        2. Over the past decade, less toxic agents such as the innovative targeted therapies, i.e.
           erlotinib or gefitinib, have the potential to improve the effectiveness and keep a good
           quality of life with a low toxicity

        3. BIBW2992 (afatinib), an aniline-quinazoline, is an epidermal growth factor receptor
           (EGFR) and human epidermal growth factor receptor 2 (HER-2) irreversible inhibitor, and
           it has activity against erlotinib-resistant isoforms having mutations in EGFR and HER-2.

        4. This molecule has shown benefits as a single agent in pre-treated patients who have
           progressed despite platinum-based chemotherapy, with a minimal toxicity compared to
           chemotherapy.

        5. BIBW2992 is associated with adverse effects similar to those for erlotinib and
           gefitinib, such as rash and diarrhea. These symptoms can reduce the quality of life (QL)
           in patients and lead to inconsistent EGFR inhibitor dose administration

        6. There is not a standard treatment for rash. However, case reports have tried to
           demonstrate the benefit in the treatment of these cutaneous injuries obtained with
           alcohol-free emollients, sunscreen with titanium dioxide or antibiotic (topic or oral)
           treatment regimens that include clindamycin or doxycycline, as well as anti-inflammatory
           drugs such as steroids and isotretinoin.

        7. In order to reduce the incidence and severity of cutaneous toxicities, we will compare
           the prophylactic antibiotic treatment using tetracycline and general dermatological
           recommendations versus using only dermatological recommendations, in patients initiating
           the treatment with BIBW2992.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of non-operable, locally advanced, recurrent or metastatic, histologically
             or cytologically documented non-small cell lung cancer (stage IIIB or IV).

               -  Patients should have an evidence of measurable disease.

               -  18 years or older

               -  Eastern Cooperative Oncology Group - Performance Status 0-3

               -  At least 12 weeks of life expectancy

               -  Patients with non-small cell lung cancer stages IIIB/IV who have received at
                  least one cycle of platinum-based, first or second line systemic standard
                  chemotherapy, and have a documented failure for this treatment.

               -  More than 2 previous chemotherapy regimens are not allowed. The patients should
                  have recovered from any toxic effect and at least 2 weeks should have elapsed
                  from last dose before their entry (14 days for vinorelbine and other vinca
                  alkaloids or gemcitabine). Patients who in the investigator's opinion are fully
                  recovered from surgery for at least 4 weeks may also be considered for the study.
                  Patients should have recovered from any severe toxicity (CTC > 1) caused by any
                  previous therapy.

               -  Granulocyte count > 1.5x 109/L and platelet count > 100x 109/L.

               -  Serum bilirubin > 1.5 upper limit of normal (ULN)

               -  AST and/or ALT > 2 ULN (or >5 x ULN when clearly attributable to presence of
                  hepatic metastases).

               -  Serum creatinine > 1.5 ULN or creatinine clearance < 60 mL/min

               -  Capability to fulfill the study and follow-up procedures.

               -  A negative pregnancy test should be obtained from all women of childbearing
                  potential within 72 hours previous to therapy beginning.

               -  Patients of reproductive potential should use effective contraceptive methods.

               -  Written (signed) informed consent to participate in the study

        Exclusion Criteria:

          -  Patients allergic to the antibiotic therapy used.

          -  Any unsteady systemic disease (including active infection, uncontrolled hypertension,
             unsteady angina, congestive cardiac failure, hepatic, renal or metabolic disease).

          -  A previous treatment using a systemic anti-tumor therapy with EGFR inhibitors
             (tyrosine kinase inhibitors).

          -  Any other malignant pathology within 5 previous years (except for carcinoma in situ of
             cervix or basal-cell type skin cancer appropriately treated).

          -  Patients with cerebral metastases or spinal marrow compression recently diagnosed
             and/or definitely surgery and/or radiation naïve-treatment patients are excluded.
             Those with previously diagnosed and treated metastasis to Central Nervous System (CNS)
             or spinal marrow compression, having an evidence of steady disease (clinically steady
             in imaging studies) are accepted for at least 2 months.

          -  Any significant ophthalmologic abnormality, especially severe dry-eye syndrome,
             keratoconjunctivitis sicca, Sjögren's syndrome, severe exposure keratitis and any
             other disorder that may increase the risk for corneal epithelial injure. Contact lens
             use during the study is not recommended. The decision to continue to use contact lens
             should be discussed with the oncologist responsible for patient treatment and the
             ophthalmologist.

          -  Patients who cannot take oral medication, requiring intravenous nutrition, who
             underwent previous surgical procedures affecting absorption, or with active peptic
             ulcer.

          -  Nursing women.