An Open Label Phase II Trial of BIBW 2992 in Patients With HER2-negative Metastatic Breast Cancer

An Open Label Phase II Trial to Assess the Efficacy and Safety of a Once Daily Oral Dose of 50 mg BIBW 2992 in Two Cohorts of Patients With HER2-negative Metastatic Breast Cancer After Failure of no More Than Two Chemotherapy Regimen

The purpose of this trial is to evaluate the efficacy, safety and pharmacokinetics of BIBW 2992, a dual, irreversible EGFR- and HER2-inhibitor, in two cohorts of patients with HER2-negative breast cancer after failure of no more than three regimen of prior chemotherapy.

Inclusion criteria:

Inclusion Criteria:

• Female patients age 18 years or older
• Histologically proven breast cancer after failure or relapse of no more than three lines of chemotherapy including adjuvant, irrespective of prior hormone therapy metastatic disease (stage IV);
• HER2-negative patients (HER2 1+ or negative, or HER2 2+ and FISH negative)
• At least one measurable tumour lesion (RECIST);
• Availability of tumour samples
• Written informed consent that is consistent with ICH-GCP guidelines and local law
• Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score 0 - 2.

Exclusion criteria:

Exclusion Criteria:

• Active infectious disease
• Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhoea
• Serious illness, concomitant non-oncological disease or mental problems considered by the investigator to be incompatible with the protocol
• Active/symptomatic brain metastases
• Cardiac left ventricular function with resting ejection fraction < 50% (below upper limit of normal)
• ANC less than 1500/mm3 platelet count less than 100 000/mm3
• Bilirubin greater than 1.5 mg /dl (>26 and#61549 mol /L, SI unit equivalent)
• AST and ALT greater than 2.5 times the upper limit of normal or greater 5 times the upper limit of normal in case of known liver metastases
• Serum creatinine greater than 1.5 mg/dl (>132 and#61549 mol/L, SI unit equivalent)
• Patients who are sexually active and unwilling to use a medically acceptable method of contraception
• Pregnancy or breast-feeding
• Concomitant treatment with other investigational drugs or other anti-cancer-therapy during this study and/or during the past two/four weeks, prior to the first treatment with the trial drug. Concurrent treatment with biphosphonates is allowed
• Previous treatment with trastuzumab, EGFR-, or EGFR/HER2-inhibitors patients unable to comply with the protocol
• Active alcohol or drug abuse
• Other malignancy within the past 5 years