HER-2 overexpressing primary operable breast cancer MedDRA version: 9.1 Level: LLT Classification code 10006187 Term: Breast cancer
Conditions
Interventions
Trade Name: HERCEPTIN®
Product Name: Trastuzumab
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Trastuzumab
Concentration unit: mg milligram(s)
Concentration type: equal
Co
Sponsors
FNCLCC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Adult female patients (= 18 years old), 2) Histologically-confirmed diagnosis of invasive breast cancer, previously untreated (patients who have been treated for cancer of the controlateral breast cancer can be included if there is at least a 2 year time interval from last systemic treatment for breast cancer before randomization into this study), 3) Candidate for breast-conserving surgery; clinical stage: cT1-3, cN0-2 4) HER-2 positive primary tumor, defined as: IHC 3+, or IHC 2+ and FISH positive (centralized confirmation), 5) Clinical stage M0 (bone scan, chest X-ray, liver ultrasound required at screening to exclude metastatic disease), 6) WHO performance status = 1 7) Adequate bone marrow function (WBC = 3.5 x109/L; ANC = 1.5 x109/L; Platelets = 100 000x109/L; Hb =10 g/dL), 8) Adequate liver function (serum bilirubin = 1.5 ULN, serum transaminases activity = 2.5 ULN; alkaline phosphatase = 2.5 ULN), 9) Adequate renal function (creatinine = 1.5 mg/dL or creatine clearance = 60 mL/min), 10) Adequate cardiac (MUGA scan or echocardiography, FEV > 55%) and pulmonary functions, 11) Potentially reproductive patients must agree to use an effective contraceptive method while on treatment 12) Women of childbearing potential must have a negative serum pregnancy test within 14 days of enrollment and/or urine pregnancy test 48 hours prior to the administration of the first study treatment, 13) Patients must be affiliated to a Social Security System, 14) Patient information and written informed consent form signed. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Patient not candidate for breast conserving surgery or patient candidate to neoadjuvant chemotherapy, 2) Patients with inflammatory breast cancer or patient with bilateral breast cancer, 3) Patients receiving concomitant anti-cancer treatments such as chemotherapy, immunotherapy/biological response modifiers, endocrine therapy and radiotherapy, 4) Known hypersensitivity to everolimus or sirolimus, to trastuzumab or lactulose, 5) = gr 3 hypercholesterolemia/hypertriglyceridemia or = gr 2 hypercholesterolemia/hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment if given), 6) Patient with uncontrolled infection, 7) Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, chronic liver or renal disease, active GI tract ulceration, severly impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air), 8) Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritonavir, Telithromycin) within the last 5 days prior to randomization, 9) Patients with a known history of HIV seropositivity, 10) Pregnant women, women who are likely to become pregnant or are breast-feeding, 11) Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial, 12) Patients who received any other investigational drugs within the 30 days prior to the screening visit, 13) Patients unwilling to participate to the biological investigations, 14) Individual deprived of liberty or placed under the authority of a tutor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the added efficacy obtained by the association of Trastuzumab with RAD001 as preoperative therapy of primary HER-2 positive breast cancer as shown by increased clinical tumor response rate.;Secondary Objective: - To compare the inhibition of the two pathways: RAS/RAF/MAPKinase and PI3Kinase/AKT/mTor. - To evaluate the pre-treatment molecular characteristics of tumor and serum or their modifications early in the treatment as being predictive of clinical response. - To compare the frequency of pathological complete response achieved in the two groups after 6 weeks of treatment. - To assess the disease-free survival at 3 years. - To evaluate safety and tolerability of the two treatment regimens. - To analyse the possible relationships between treatment toxicity and constitutional gene polymorphisms linked to the administered agents. - To analyse the possible relationships between response and molecular pharmacodynamic assessments: proteomics (blood samples), Bioplex protein array (tumor) and IHC (tumor). - To analyse the drug levels and pharmacokinetic assessments of the association RAD001 and trastuzumab.;Primary end point(s): To evaluate the added efficacy obtained by the association of Trastuzumab with RAD 001 as preoperative therapy of primary HER-2 positive breast cancer as shown by increased clinical tumor response rate (WHO criteria). Clinical response will be measured by echography within 1 week prior to surgery. WHO criteria will be used without confirmation. | — |
Countries
France
Outcome results
None listed