BIBW 2992 (Afatinib) in Combination With Pemetrexed in Advanced Solid Tumours
Condition: Neoplasms
Intervention: BIBW 2992 low dose; BIBW 2992 high dose; pemetrexed; pemetrexed; BIBW 2992 high dose 6 day; pemetrexed; pemetrexed; pemetrexed; pemetrexed; BIBW 2992 low dose 6 day; BIBW 2992 medium dose 6 day; BIBW 2992 medium dose
Intervention description: patient receives low dose BIBW 2992 po daily on day 1 of 21 day cycle; patient receives high dose BIBW 2992 po daily on day 1 of 21 day cycle; given intravenously on day 1 of a 21 day cycle; given intravenously on day 1 of a 21 day cycle; patient receives high dose BIBW 2992 po daily on days 1-6 on 1 of 21 day cycle; given intravenously on day 1 of a 21 day cycle; given intravenously on day 1 of a 21 day cycle; given intravenously on day 1 of a 21 day cycle; given intravenously on day 1 of a 21 day cycle; patient receives low dose BIBW 2992 po daily on days 1-6 on day 1 of 21 day cycle; patient receives medium dose BIBW 2992 po daily on day1 to 6 of a 21 day cycle; patient receives medium dose BIBW 2992 po daily on day 1 of 21 day cycle
Intervention MeSH terms: Pemetrexed; Afatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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 criteria:

        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