HER2-neu overexpressing metastatic breast cancer after previous trastuzumab use MedDRA version: 16.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Anfinitor 5 mg Tabletten
Product Name: Everolimus / RAD001 5 mg
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor cod
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent; - HER2+ status defined as IHC 3+ staining or in situ hybridization positive. Note: The pathology report confirming HER2+ status must be available at the study center prior to randomization; - Patients with resistance to trastuzumab - Prior taxane therapy. - Patients with an ECOG performance status of 0 - 2; - Patients with measurable disease as per RECIST criteria; - Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study; - Patients must meet laboratory criteria within 21 days prior to randomization Other protocol-defined inclusion criteria may apply. 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 472 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 97
Exclusion criteria
Exclusion criteria: - Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer; - More than three prior chemotherapy lines for advanced disease. - Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus - Peripheral neuropathy = grade 2 at randomization - Active cardiac disease - History of cardiac dysfunction - Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer - Known hypersensitivity to any study medication - Breastfeeding or pregnant Other protocol-defined exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the combination of everolimus, vinorelbine and trastuzumab to vinorelbine and trastuzumab alone with respect to progression-free survival in women with HER2/neu overexpressing locally advanced or metastatic breast cancer who are resistant to trastuzumab and have been pre-treated with a taxane;Secondary Objective: Key secondary objective of this study is to compare the two treatment arms with respect to overall survival (OS). Other secondary objectives are to evaluate the two treatment arms with respect to • Objective response rate (ORR) • Time to deterioration of ECOG performance status • Safety • Change in QoL scores over time • Clinical benefit rate (CBR) • Duration of response (DoR) • Time to response • To evaluate the impact of co-administration of everolimus to vinorelbine pharmacokinetics in the presence of trastuzumab in a subgroup of patients • To evaluate the impact of co-administration of everolimus to trastuzumab pharmacokinetics in the presence of vinorelbine in a subgroup of patients • To evaluate the concentrations of everolimus at predose (Cmin) and at 2 hours post-dose (C2h) when co-administrated with vinorelbine and trastuzumab in a subgroup of patients ;Primary end point(s): Progressive-free survival (PFS), defined as the time from the date of randomization to the date of first radiologically documented tumor progression or death from any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: Every 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival (OS), defined as the time from date of randomization to the date of death from any cause. 2. Overall response rate (ORR) defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST 3. Patient reported outcome (PRO) questionnaires 4. Clinical benefit rate (CBR) defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks. 5. Laboratory assessments (hematology, chemistry, coagulation), AEs graded by CTCAE version 3.0 or equivalent;Timepoint(s) of evaluation of this end point: 1. Every 3 months 2. Every 6 weeks 3. Every 6 weeks 4. Every 6 weeks 5. Continuous until 28 days after the last dose of study drug | — |
Countries
Argentina, Australia, Belgium, China, Czech Republic, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Poland, Singapore, Slovakia, Spain, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed