Trastuzumab-resistant HER2-overexpressing metastatic breast cancer
Conditions
Interventions
Trade Name: Tyverb
Product Name: Tyverb
Product Code: GW572016
Pharmaceutical Form: Film-coated tablet
Trade Name: Herceptin
Pharmaceutical Form: Powder for concentrate for solution for infusion
Tra
Sponsors
Berufsverband der niedergelassenen gynäkologischen Onkologen in Deutschland e.V.; BNGO e.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Women with histologically confirmed breast cancer; measurable metastatic disease; HER2-positive (IHC 3+ or ISH positive); Hormone receptor-negative; prior treatment with trastuzumab, anthracycline and taxanes; progression on trastuzumab as first-line or second-line therapy; no prior treatment with lapatinib within last 6 months; Adequate hematologic, renal and liver function; normal cardiac function with LVEF of =50%; ECOG performance status 0-1; No evidence of brain metastases (asymptomatic metastases that have been clinically stable for 3 months are allowed); no significant cardiovascular disease or other serious medical condition; written informed consent to participate in the trial and to the donation of formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer available for central testing. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • 1. Patients with confirmed brain metastases or a history of primary central nervous system tumours or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases. Patients with treated brain metastases that are asymptomatic and have been clinically stable for 3 months will be eligible for protocol participation. • 2. Hormone receptor-positive patients or prior treatment with lapatinib within the last 6 months • 3. More than 2 line of trastuzumab-based treatment for advanced disease • 4. Significant cardiovascular disease, such as ? History of myocardial infarction, acute coronary syndromes (including unstable angina), or history of coronary angioplasty/stenting/bypass grafting within past 6 months. ? History of symptomatic congestive heart failure (CHF) New York Heart Association (NYHA) Classes II-IV or LVEF 100 mmHg) ? Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy, or cardiomyopathy • 5. QTc prolongation defined as a QTc interval >460 msecs or other significant ECG abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia (ventricular rate <50 beats/min) • 6. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) • 7. Malabsorption syndrome or other condition that would interfere with enteral absorption • 8. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent. • 9. Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol. • 10. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 6 months from the date of randomisation.;Main Objective: Estimate the clinical benefit of lapatinib plus trastuzumab compared to lapatinib plus capecitabine as measured by investigator-assessed progression-free survival (PFS);Secondary Objective: • Evaluate overall survival of lapatinib plus trastuzumab relative to lapatinib plus capecitabine • Determine clinical objective response and clinical benefit rate of lapatinib plus trastuzumab compared to lapatinib plus capecitabine • Determine safety and tolerability of the experimental study treatment compared to lapatinib plus capecitabine in this population • Compare the differences in health-related quality of life (HRQL) and pain symptoms for patients by treatment assignment ;Primary end point(s): The 6-month PFS-rate (PFS6) will be the number of patients without disease progression or death within 6 months from the date of randomization, divided by the number of patients in the respective analysis population. For the purpose of the analysis patients who are lost to follow-up or deceased in at or before 6 months after randomization will be counted as “disease progression”. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression free survival • Overall survival and overall survival rate at 12 months • Clinical objective response • Duration of response and clinical benefit • Patient reported outcomes by European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire QLQ-C30 ;Timepoint(s) of evaluation of this end point: Timepoint of disease progression. | — |
Countries
Germany
Contacts
Public ContactCRO-Clinical Research Organization
OnkoDataMed GmbH - ODM
Outcome results
None listed