Women with stage II-III, HER2/ErbB2-positive primary breast cancer elegible for neoadjuvant treatment. MedDRA version: 20.0 Level: PT Classification code 10006279 Term: Breast neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: METFORMINA TEVA 850 mg comprimidos recubiertos con película
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: METFORMINA HIDROCLORURO
Other descriptive name: METFORMIN HYDROCHLO
Sponsors
Institut Català d'Oncologia
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Mujeres. 2. Edad 18-75 años. 3. Puntuación 0-1 de la clasificación ECOG (Eastern Cooperative Oncology Group) (ver ApéndiceB). 4. Cáncer de mama invasivo confirmado histológicamente (incluido el cáncer de mama inflamatorio y el cáncer de mama multifocal:) - Tumor primario mayor de 2 cm. de diámetro, medido por examen clínico y por mamografía o ecografía. - Cualquier N - Sin evidencia de metástasis (M0), (un ganglio supraclavicular aislado afectado está permitido). Se seguirá la 7ª edición del AJCC Cancer Staging Manual (ver Apéndice C). 5. Sobre-expresión y/o amplificación de HER2 en el componente invasivo del tumor primario, definido según el siguiente criterio: - IHC 3+ - IHC 2+ y FISH/CISH positivo 6. Estado conocido de los receptores hormonales. 7. Función hematopoyética: - Recuento absoluto de neutrófilos ?1,5 x109/L - Recuento de plaquetas ?100 x109/L - Hemoglobina ?9 g/dl 8. Función hepática: - Bilirrubina sérica total ?1,5 x límite superior normal (LSN). - AST y ALT ?2,5 x LSN - Fosfatasa alcalina ?2,5 x LSN - Glucosa en ayunas ?70 mg/dl 9. Función renal: - Creatinina?1,5 x LSNCódigo del protocolo: METTEN-01 Confidencial Versión 2 Fecha 15/05/2011 23 10. Cardiovascular: - FEVI basal ?50% medida mediante ecocardiografía (ECO) o rastreo MUGA (del inglés, Multiple Gate Acquisition) 11. 20 ?IMC? 30 12. Prueba de embarazo negativa en los 7 días previos a la aleatorización (en las mujeres potencialmente fértiles). 13. Las mujeres fértiles deben utilizar un método anticonceptivo efectivo. 14. Consentimiento informado por escrito. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 133 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1. Prior treatment for primary invasive breast cancer. 2. Bilateral breast cancer. 3. Precedent medical history less than 10 years or present history for other malignant neoplasia, except in situ carcinoma of the cervix and basocellular and epidermoid skin carcinoma. Previous diagnosis of melanoma or breast cancer are excluded. 4. Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarct, uncontrolled hypertension, dyspnea at rest, or chronic therapy with oxygen. 5. Metabolic disease (diabetes mellitus type I or II, obesity (BMI ? 30), hyperglycemia (preprandial glucose >128 mg/dl), hypercholesterolemia or hypertrigliceridemia ? grade 3 according to CTC-NCIC version 3.0. 6. History of metabolic acidosis. 7. Chronic neumopathy or respiratory restriction. 8. Concurrent disease or condition that would make the patient inappropriate for study participation or any serious medical disorder that would interfere with the patient's safety. 9. Active or uncontrolled infection. 10. Enolism. (daily media consumption of more than 3 alcoholic beverage intake) 11. Hepatic insufficiency. 12. Renal insufficiency (calculated CrCl < 60 mL/min). 13. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent by the patient. 14. Malabsorption syndrome, with disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. 15. Concurrent treatment with therapies that can alter insulin levels (including chronic treatment with oral corticoids). 16. Concurrent treatment with an investigational drug or participation in another therapeutic clinical trial. 17. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trastuzumab, metformin or their excipients. Glucose or galactos absorption problems and hereditary galactose intolerance. 18. Pregnant or lactating women. and galactosemia o hereditary galactosemia intolerance. 19. Sociologic, familiar or geographical conditions that may compromise clinical trial protocol compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the efficacy of adding metformin concomitantly with chemotherapy and trastuzumab in the neoadjuvant treatment of patients with HER2-positive operable breast cancer as measured by the number of pathological complete responses.;Secondary Objective: - To assess the safety and tolerability of both treatment regimens. - To determine the 5-years Disease Free Survival (DFS) from last patient randomization. - To evaluate the cardiac toxicity associated to both treatment schedules. - To examine biomarkers´ activity/expression functionally related with AMPK. mTor signaling pathway in tumor tissue - To determine circulating insulin levels in patients? serum .;Primary end point(s): -Pathological Complete Response Rate (pCR) . Percentage of patients who present pathological complete response, defined as the absence of infiltrating carcinoma in resected materials and the axilla or the exclusive presence of in situ non-invasive cancer in resected material (number of patients with pCR)/(total patient numbers according to per protocol population) x 100;Timepoint(s) of evaluation of this end point: It will assess the pathological response in surgical specimen obtained after completion of neoadjuvant therapy. The first efficacy analysis will be performed when available 37 responses evaluated in both groups of treatment, according to two-step method of Jung | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.-Safety and Tolerability. To determine the safety profile from adverse events reported by patients. Every AE will be recorded until 28 days after last study drug intake. Non serious AE related with the drug medication appeared up to 6 month after the last study drug intake must be reported. 2.- 5 year disease-free survival from diagnosis: probability of disease relapse or death by any cause. 3.- Cardiotoxicity rate. Number of patients with cardiotoxicity (according to CTCAE V4.0 criteria) divided among the total patients number or the total number of patients per protocol ( x100). 4.- Biomarkers 5.- Insulin levels.;Timepoint(s) of evaluation of this end point: It will be held at the end when making the final statistical analysis, after collecting all the study data. | — |
Countries
Spain
Contacts
Public ContactNeus Bosch Pont
Institut Català d'Oncologia de Girona
Outcome results
None listed