An Open Label Phase II Trial of BIBW 2992 (Afatinib) in Genetically Pre-screened Cancers With EGFR and/or HER2 Gene Amplification or EFGR Activating Mutations.

Inclusion Criteria

Inclusion criteria:

There are 2 Steps in the screening process:

Step 1 Inclusion criteria for pre-screening:

1. Histologically confirmed diagnosis of advanced cancer of one of the following four
tumor type categories:

Category 1, Gastric, GE junction, or Esophageal cancer Category 2, Biliary or
gallbladder cancer Category 3, TCC urothelial tract, and Category 4, Gynecological
cancers

2. Measurable disease by RECIST criteria.

3. Willingness and ability to give written informed consents consistent with ICHGCP
guidelines.

4. Life expectancy of at least three (3) months.

5. Eastern Cooperative Oncology Group performance score 0, 1 or 2.

6. Age >18 years.

Step 2 Inclusion criteria for enrollment:

Patients who have tested positive for FISH and are considered candidate for this trial
must meet all of the following inclusion criteria:

1. Histologically confirmed diagnosis of advanced cancer of one of the following four
tumor type categories:

Category 1, Gastric, GE junction, or Esophageal cancer Category 2, Biliary or
gallbladder cancer Category 3, TCC urothelial tract, and Category 4, Gynecological
cancers

2. Documented failure to respond or progression of underlying cancer after at least one
line of prior chemotherapy.

3. EGFR and/or HER2 gene amplification by FISH testing or patients with tumors that
harbor known activating EGFR mutations.

4. Measurable disease by RECIST criteria.

5. Willingness and ability to give written informed consents consistent with ICH-GCP
guidelines.

6. Life expectancy of at least three (3) months.

7. Eastern Cooperative Oncology Group performance score 0, 1 or 2.

8. Age >18 years.

Exclusion criteria:

1. Prior treatment with gefitinib, erlotinib, lapatinib and/or other EGFR TKIs.

2. Treatment with cytotoxic anti-cancer-therapies or investigational drugs during the
last four weeks prior to the first treatment with the trial drug. (a shorter duration
may be considered for patients treated with oral, non cytotoxic drugs on an
individual basis and upon discussion between the principal investigator and sponsor)

3. Inability to take BIBW 2992 by mouth (BIBW 2992 may not be crushed or administered
via Gastrostomy-tube)

4. Chronic diarrhea or other gastrointestinal disorders that may interfere with the
absorption of the trial drug.

5. History of other malignancies unless free of disease for at least 3 years (except for
appropriately treated superficial non-melanoma skin cancer and surgically cured
cervical cancer in situ).

6. History or presence of clinically relevant cardiovascular abnormalities such as
uncontrolled hypertension, congestive heart failure NYHA classification of 3,
unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6
months prior to randomization.

7. Resting left ventricular ejection fraction <50% OR below the institution's lower
limit of normal (if the institutions lower limit is above 50%), measured by MUGA scan
or echocardiogram.

8. Active infectious disease

9. Serious illness, concomitant non-oncological disease or mental problems considered by
the investigator to be incompatible with participation in this trial.

10. Active/symptomatic brain metastases. Patients with a history of treated brain
metastases must have stable or normal brain MRI scan at screening and be at least
three months post-radiation or surgery for brain metastasis.

11. Absolute Neutrophil Count (ANC) less than 1,000/mm3.

12. Platelet count less than 100,000/mm3.

13. Hemoglobin Level less than 9.0 grams/dl.

14. Total Bilirubin greater than 1.5 mg/dl; higher Total Bilirubin values may be
acceptable for patients with known Gilbert¿s disease, approval by the PI and sponsor
will be necessary.

15. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3
times the upper limit of normal; or 5 times the upper limit of normal in patients
with neoplastic liver involvement.

16. Serum creatinine greater than 1.5 x upper limit of normal for the institution.

17. Patients who are sexually active and unwilling to use simultaneously two medically
acceptable method of contraception, one of which being a barrier type method such as
condom.

18. Pregnancy or breast-feeding.

19. Patients unable to comply with the protocol

20. Active alcohol and/or substance abuse.

21. Continuation of therapy-related toxicities from prior anti cancer therapies, prior
surgery, of CTCAE Grade >=2 at the time of the first administration of the trial
drug.

22. Patients with known pre-existing interstitial lung disease.

23. Requirement for treatment with any of the prohibited concomitant medications:
additional experimental anti-cancer treatment and/or standard chemotherapy,
immunotherapy, hormone treatment or radiotherapy; P-gp inhibitors