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Phase II randomised, open-label, multicentric clinical trial of neoadjuvant treatment comprising chemotherapy and trastuzumab with or without metformin, in women with HER2/ErbB2 positive primary breast cancer.

Phase 1
Conditions
Women with stage II-III, HER2/ErbB2-positive primary breast cancer elegible for neoadjuvant treatment.
MedDRA version: 20.0Level: PTClassification code 10006279Term: Breast neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2011-000490-30-ES
Lead Sponsor
Institut Català d'Oncologia
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
Female
Target Recruitment
Not specified
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

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.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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