Metastatic breast cancer
Conditions
Interventions
Product Name: lapatinib
Product Code: GW572016
Pharmaceutical Form: Film-coated tablet
CAS Number: 388082-78-8
Current Sponsor code: GW5
Sponsors
GlaxoSmithKline R&D Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to give signed informed consent. 2. Female = 18 years. 3. Metastatic breast cancer, histologically/cytologically confirmed. If the disease is restricted to a solitary lesion, its neoplastic nature must be confirmed by cytology or histology. 4. Stage IV breast cancer that has progressed in either the adjuvant or metastatic setting. Prior therapies must include, but are not limited to: - Taxane-containing regimen for at least 4 cycles, or 2 cycles provided disease progression occurred while on taxane. - Anthracycline-containing regimen for at least 4 cycles, or 2 cycles provided disease progression occurred while on anthracycline. 5. Subjects must have received and progressed following treatment with at least TWO trastuzumab plus cytotoxic chemotherapy regimens in the metastatic setting. The most recent treatment must have contained trastuzumab, either alone or in combination with other chemotherapy, for at least 6 weeks of standard doses in the metastatic setting, and subjects must have progressed while on this regimen. Trastuzumab administered in the adjuvant setting is not exclusionary, but for eligibility, trastuzumab also must have been administered in the metastatic setting. 6. Subjects must have archived tumour tissue available for testing. 7. Documented amplification of the ErbB2 gene by fluorescence in situ hybridization (FISH) in primary or metastatic tumor tissue. Amplification may be documented by a local laboratory or the central laboratory for randomisation into the study. Additionally, a tissue sample must be sent to the central laboratory before a subjects enrollment on the study. 8. Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid Tumors). 9. Subjects with stable CNS metastases defined as asymptomatic and off systemic steroids and anticonvulsants for at least 3 months; 10. Radiotherapy if received within 2 weeks prior to initiation of IMP to a limited area (e.g., palliative treatment for painful disease) other than the sole site of measurable disease is allowed; however, subject must have completed treatment and recovered from all treatment-related toxicities prior to administration of the first dose of IMP. 11. Except for prior trastuzumab treatment, at least 3 weeks since prior chemotherapy, immunotherapy, biologic therapy, hormonal therapy for cancer, or surgery (except for minor surgical procedures) before beginning investigational product. Subjects must have recovered or stabilized sufficiently from treatment-related toxicities prior to administration of the first dose of investigational product. 12. Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of IMP. Prophylactic use of bisphosphonates in is permitted only for the treatment of osteoporosis. 13. ECOG Performance Status of 0 or 1. 14. Able to swallow and retain oral medication. 15. Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive. 16.
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating females. 2. Prior therapy with an ErbB1 and/or ErbB2 inhibitor other than trastuzumab. 3. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded. 4. History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. 5. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety. 6. Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment. 7. Active or uncontrolled infection. 8. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent. 9. Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure. 10. Known history or clinical evidence of leptomeningeal carcinomatosis. 11. Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy). 12. Concurrent treatment with an investigational agent or participation in another clinical trial. 13. Used an investigational drug within 3 weeks or 5 half-lives, whichever is longer, preceding the first dose of investigational product. 14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab or lapatinib or their excipients.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate and compare the anti-tumour activity, in terms of progression-free survival, of trastuzumab plus lapatinib versus lapatinib monotherapy in subjects with ErbB2 amplified metastatic breast cancer.; Secondary Objective: - To evaluate and compare the two treatment groups with respect to the following: overall survival, tumor response rate (complete (CR) or partial (PR)), clinical benefit (CR, PR, and stable disease for at least 6 months), time to response, duration of response. - To determine the qualitative and quantitative toxicities associated with oral lapatinib administered daily in combination with trastuzumab versus lapatinib monotherapy. - To collect and store serum specimens for comparing baseline and on-treatment serum concentrations of ErbB1 and ErbB2 extracellular domains, for potential proteomic analysis, to identify changes in the protein profile and correlate to treatment response. - To further characterize the patient population by determination of intra-tumoral expression of ErbB1, ErbB2, and downstream biomarkers. - To evaluate quality of life status within the study population and compare between treatment groups. ;Primary end point(s): Progression-free survival | — |
Countries
Austria, Czech Republic, Finland, Germany, Greece, Hungary, Italy, Spain, United Kingdom
Outcome results
None listed