Phase II Trial of BIBW 2992 in Patients With HER2-positive Metastatic Breast Cancer After Failure of Trastuzumab Therapy

Inclusion Criteria:

1. Male or female patients with confirmed diagnosis of Stage IIIB or IV HER2-positive
metastatic breast cancer(HER2 2+ and FISH positive or HER2 3+).

2. Patients must have progressed following receipt of prior standard trastuzumab
treatment or standard chemotherapy in conjunction with trastuzumab. Patients with
visceral disease or rapid progression should not be included if they have not had
previous chemotherapy in addition to trastuzumab. Patients who are intolerant to
trastuzumab and who have received adequate chemotherapy and/or hormone therapy are
eligible upon progression.

3. Age 18 years or older.

4. Life expectancy of at least four (4) months.

5. Written informed consent that is consistent with ICH-GCP guidelines.

6. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance Score 0, 1 or 2.

7. Patients should not have received treatment with chemotherapy or immune therapy
within the last 4 weeks (2 weeks for trastuzumab). Patients should not have received
treatment with hormone therapy within the last 2 weeks.

8. Patients must have recovered from any therapy-related toxicities from previous
chemo-, hormone-, immuno-, or radiotherapies to CTC less than or equal to Grade 1.

9. Patients must have recovered from previous surgery.

10. Patients must have measurable disease as defined by RECIST criteria.

Exclusion Criteria:

1. Active infectious disease.

2. Gastrointestinal disorders that may interfere with the absorption of the study drug
or chronic diarrhea.

3. Serious illness or concomitant non-oncological disease considered by the investigator
to be incompatible with the protocol.

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

5. Cardiac left ventricular function with resting ejection fraction <50%.

6. Absolute neutrophil count (ANC) less than 1500 cells/mm3.

7. Platelet count less than 100 000 cells/mm3.

8. Bilirubin greater than 1.5 mg/dl (>26 micromol /L, SI unit equivalent).

9. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than
three times the upper limit of normal.

10. Serum creatinine greater than 1.5 mg/dl (>132 micromol/L, SI unit equivalent).

11. Women and men (and their partners) who are sexually active and unwilling to use a
medically acceptable method of contraception.

12. Pregnancy or breast-feeding.

13. Treatment with other investigational drugs; chemotherapy, immunotherapy, radiotherapy
or hormone therapy (including LHRH agonists, or other hormones taken for breast
cancer), or participation in another clinical study within the past 4 weeks before
start of therapy or concomitantly with this study. Treatment with bisphosphonates is
allowed.

14. Prior treatment with an EGFR- or HER2 inhibiting drug (except trastuzumab).

15. Patients unable to comply with the protocol.

16. Active alcohol or drug abuse.

17. Patients with history of other malignancy (except for appropriately treated
superficial basal cell skin cancer and surgically cured cervical cancer in situ)
unless free of disease for at least 3 years.