Breast cancer is the most frequently diagnosed malignancy and the second most common cause of cancer related deaths in women. HER2 is a member of the epidermal growth factor receptor (EGFR) family that includes EGFR/HER1, HER2, HER3 and HER4, all being receptor tyrosine-protein kinases. The oncogenic role of HER2 has been extensively documented in breast cancer, where it is overexpressed in 25% to 30% of breast cancers.
Conditions
Interventions
Product Name: HKI-272
Pharmaceutical Form: Capsule*
CAS Number: Not assigned
Current Sponsor code: WAY-179272-B
Other descriptive name: HKI-272
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pathologic diagnosis of breast cancer and current stage IIIB, IIIC, or IV breast cancer not curable with available therapy. 2. Progression following at least six weeks of standard doses of Herceptin (trastuzumab) or a Herceptin containing regimen in a metastatic or locally advanced setting; or progression on or following Herceptin containing adjuvant therapy (Arm A only). Up to 20 subjects with HER2+ breast cancer with prior lapatinib exposure may be enrolled in ARM A only. 3. Tumor tissue available and adequate for HER2 gene amplification. 4. HER2 gene amplified tumor by FISH (fluorescence in situ hybridization). 5. At least 1 measurable lesion as defined by modified RECIST criteria. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 (not declining within past 2 weeks). 7. Women aged >= 18 years. 8. Life expectancy of at least 12 weeks. 9. Recovery from all clinically significant acute adverse effects of prior therapies (excluding alopecia). 10. Screening laboratory values within the following parameters: ANC >= 1.5 x 10^9/L (1,500/mm^3) Platelet count >= 75 x 10^9/L (75,000/mm^3) Hemoglobin >= 8.0 g/dL (80g/L) Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior treatment with Herceptin or any HER2-targeted treatment (Arm B only) 2. More than 4 prior cytotoxic chemotherapy treatment regimens for relapsed or metastatic disease. 3. Major surgery, chemotherapy, radiotherapy, investigational agents or other cancer therapy within 1 week of treatment day 1. 4. Extensive visceral disease including bilateral diffuse lymphangitic involvement of the lung with more than 50% lung involvement, extensive hepatic involvement defined as involvement of more than one third of the liver confirmed by CT or MRI scan. 5. Subjects with bone or skin as the only site of measurable disease 6. Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (subjects with a history of CNS metastases or cord compression are allowable if they have been definitively treated and are clinically stable for at least 4 weeks before first dose of test article). 7. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association [NYHA] functional classification of >=3), angina, myocardial infarction, or ventricular arrhythmia. 8. Left ventricular ejection fraction less than 50% measured by multigated blood pool imaging of the heart (MUGA) scanning or echocardiogram (ECHO) 9. QTc interval > 0.47 second 10. Prior treatment with anthracyclines with a cumulative dose of doxorubicin or equivalent > 400 mg/m^2 11. Pregnant or breast feeding women 12. Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (e.g, Crohn’s disease, malabsorption, or Grade >=2 diarrhea of any etiology at baseline) 13. Inability or unwillingness to swallow the HKI-272 capsules 14. Evidence of significant medical illness or abnormal laboratory finding that would, in the investigator’s judgment, make the subject inappropriate for this study. Examples include, but are not limited to, serious active infection (i.e. requiring intravenous antibiotic or antiviral agent), uncontrolled major seizure disorder, any other active malignancy (except for breast cancer).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the sixteen (16) week progression-free survival (PFS) rate for HKI-272 in women with advanced breast cancer.;Secondary Objective: · Further evaluate the safety of HKI-272 · Assess additional efficacy parameters: objective response rate, clinical benefit rate (CR +PR +SD), duration of response. · Assess health outcomes endpoints by administering quality of life questionnaires · Evaluate the pharmacokinetics of HKI-272;Primary end point(s): Clinical activity will be assessed using the primary endpoint of 16 week Progression-Free Survival (PFS) rate. Progression status will be determined using modified RECIST guidelines. The primary efficacy analysis will be based on the intent-to-treat (ITT) and evaluable populations. The ITT population is defined as all subjects enrolled in the study. | — |
Countries
Belgium, France
Outcome results
None listed