BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1)
Condition: Carcinoma, Non-Small-Cell Lung
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: placebo; BIBW 2992
Intervention description: Patients receive placebo once daily; Patients receive afatinib tablets once daily, and can reduce dose for adverse event management. Afatinib is given once daily, continuously until disease progression or unacceptable toxicity.
Intervention MeSH terms: Afatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 585.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized, double-blind, multi-center Phase IIb/III trial will be performed in patients
      with NSCLC who have received previous treatment with at least one but not more than two lines
      of cytotoxic chemotherapy (one line must have been a platinum-containing regimen) and either
      gefitinib or erlotinib for a period of at least 12 weeks and then progressed.

      The primary objective of this randomized trial is to determine the efficacy of BIBW 2992 as a
      single agent (Arm A) as compared to a matching placebo (Arm B) in this patient population.
      Patients on both treatment arms will receive best supportive care in addition to study
      treatment.

      Patients enrolled into the trial will be treated and followed until death or lost to
      follow-up.
    

Eligibility criteria:

        Inclusion criteria:

          1. Patients with pathologic confirmation of NSCLC Stage III-B (with pleural effusion) or
             Stage IV adenocarcinoma who have failed at least one but not more than two lines of
             cytotoxic chemotherapy (including adjuvant chemotherapy). One of the chemotherapy
             regimens must have been platinum-based.

          2. Progressive disease following at least 12 weeks of treatment with erlotinib (Tarceva®)
             or gefitinib (Iressa®)

          3. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance Score 0, 1 or 2

          4. Patients with at least one tumor lesion that can accurately be measured by magnetic
             resonance imaging (MRI), or computed tomography (CT) in at least one dimension with
             longest diameter to be recorded as >20 mm using conventional techniques or >10 mm with
             spiral CT scan

          5. Male and female patients age >18 years

          6. Life expectancy of at least three (3) months

          7. Written informed consent that is consistent with ICH-GCP guidelines

        Exclusion criteria:

          1. Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of treatment Day 1

          2. Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance
             non-cancer therapy) or immunotherapy within the past 4 weeks

          3. Active brain metastases

          4. Significant or recent acute gastrointestinal disorders with diarrhea

          5. Patients who have any other life-threatening illness or organ system dysfunction,

          6. Other malignancies diagnosed within the past five (5) years

          7. Radiotherapy within the past 2 weeks prior to treatment

          8. History of clinically significant or uncontrolled cardiac disease

          9. Adequate ANC and platelet count

         10. Adequate liver and kidney function

         11. Patients with any serious active infection including known HIV, active hepatitis B or
             active hepatitis C