Clinical Study for the Treatment of Breast Cancer: the Patient Will Receive Afatinib Plus Letrozole or Letrozole Alone
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Intervention: Letrozole; Afatinib
Intervention MeSH terms: Letrozole; Afatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to compare the efficacy of treatment with afatinib plus letrozole
      to treatment with letrozole alone in women diagnosed with a specific type of breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed and dated informed consent.

          -  Postmenopausal females, 18 years of age or older.

          -  Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with
             evidence of locally recurrent disease not amenable to resection or radiation therapy
             with curative intent, or metastatic disease.

          -  HER2 negative breast cancer. Central testing (required for all subjects) must
             demonstrate that the tumor is HER2 negative by FISH or Immunohistochemistry (IHC).

          -  ER positive breast cancer. Central testing (required for all subjects) must
             demonstrate that the tumor is ER+ with low expression (H-score [1-159]).

          -  Paraffin-embedded tumor block(s) or 15 to 20 unstained slides available for
             centralized assessment of ER, PR, and HER2.

          -  Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)
             1.1 or bone-only non measurable disease.

          -  Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.

          -  Adequate hematological, hepatic and renal functions.

          -  Baseline left ventricular ejection fraction (LVEF) 50%.

          -  Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and other trial procedures.

        Exclusion Criteria:

          -  Brain metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal
             disease.

          -  Prior treatment with any type of systemic therapy for advanced disease.

          -  Prior treatment with letrozole in (neo)adjuvant setting with disease-free interval ≤
             12 months from completion of treatment until randomization.

          -  Prior treatment with any anti HER-family targeted therapy in (neo)adjuvant setting.

          -  Any concurrent or previous malignancy within 5 years prior to randomization, except
             for adequately and radically treated basal or squamous skin cancer, or carcinoma in
             situ of the cervix, or other non-invasive/in-situ neoplasm.

          -  Non-measurable disease according to RECIST 1.1, with the exception of bone-only
             non-measurable disease.

          -  Known pre-existing interstitial lung disease.

          -  Significant or recent acute gastrointestinal disorders with diarrhea as a major
             symptom.

          -  History or presence of clinically relevant cardiovascular abnormalities as per
             investigator assessment.

          -  Any other concomitant serious illness or organ system dysfunction as per investigator
             assessment

          -  Any contraindication to oral agents.

          -  Active hepatitis B infection, active hepatitis C infection or known HIV carrier.

          -  Known or suspected active drug or alcohol abuse.

          -  Known hypersensitivity to afatinib or letrozole or the excipients of any of the trial
             drugs.

          -  Concomitant treatment with strong inhibitor of P-gp.

          -  Any ongoing acute clinically significant toxic effect of prior anticancer therapy or
             any persisting complication of prior surgery.

          -  Subjects with known history of keratitis, ulcerative keratitis or severe dry eye.

          -  Participation in the active phase of other clinical trials of investigational agents
             in which last study treatment was administered within 2 weeks prior to randomization