Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

Clinical trial: BIBW 2992 (Afatinib) in Combination With Pemetrexed in Advanced Solid Tumours

Summary: This Phase I study will investigate the safety of BIBW 2992 in combination with standard dose pemetrexed (500mg/m2) given on a 21 day cycle in patients with advanced solid cancers. BIBW 2992 will be given on two different dose schedules; dosing on days 1-21 and dosing on days 1 to 6 of a 21 day cycle.
  The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), including BIBW 2992 have demonstrated efficacy in solid tumors including non-small cell lung cancer (NSCLC). In addition, pemetrexed has demonstrated efficacy and has been approved as single agent chemotherapy in second-line NSCLC patients with adenocarcinoma. The data obtained from this trial shall allow for a conclusion as to whether BIBW 2992 may be safely administered in advanced cancer patients in combination therapy with pemetrexed.


Eligibility: Inclusion criteria:
  1. Age 18 or older.
  2. Eastern cooperative oncology group performance status of 0-2.
  3. Life expectancy of at least 12 weeks.
  4. Measurable disease according to Response evaluation criteria in solid tumors 1.1 criteria.
  5. Written informed consent
  Exclusion criteria:
  1. Treatment with an investigational drug within the past 28 days prior to the start of therapy
  2. Persisting toxicities which are clinically significant from previous therapy
  3. Patients who are unwilling or unable to take folic acid and vitamin B12 supplementation
  4. Active brain metastases
  5. Other active malignancy diagnosed within the past 3 years
  6. Concomitant intercurrent illnesses that would limit compliance with trial requirement
  7. Patients unable or unwilling to interrupt concomitant administration of Non-steroidal anti-inflammatory drugs (NSAIDS) as per pemetrexed prescribing information
  8. Patients who have received prior therapy with BIBW 2992
  9. Left ventricular function by echocardiogram or Multiple gated acquisition scan (MUGA) less than institutional lower limit of normal
  10. Absolute neutrophil count (ANC) less than 1,500/mm3
  11. Platelet count less than 100,000/mm3
  12. Hemoglobin less than 90g/L
  13. Total bilirubin less than 26µmol/L
  14. Alanine amino transferase (ALT) and/or aspartate amino transferase (AST) greater than 2.5 X ULN, except in case of known liver metastasis where maximum 5 X ULN is acceptable
  15. Serum creatinine level greater than 133µmol/L and/or creatinine clearance (measured or calculated) less than 45 ml/min
  16. History or recent gastrointestinal bleeding, obstruction or perforation or malabsorption syndrome and must be able to swallow the BIBW 2992 in whole by mouth.
  17. History of interstitial lung disease
  18. Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
  19. Pregnancy or breast feeding
  20. Known or suspected active alcohol or drug abuse
  21. Patients unable to comply with the protocol
  22. Has a diagnosis of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
  23. Any known hypersensitivity to the trial drugs or their excipients

Relevance to patient case: possibly relevant