- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01793948
Metformin Hydrochloride vs. Placebo in Overweight or Obese Patients at Elevated Risk for Breast Cancer
A Double Blind Prospective Study of Metformin vs. Placebo in Overweight or Obese Post-menopausal Women at Elevated Risk for Breast Cancer
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
PRIMARY OBJECTIVES:
I. To determine the changes in the signal pathway profiling of breast tissue using reverse phase proteomics in tissue biopsy of overweight or obese women at elevated risk for breast cancer treated with metformin (metformin hydrochloride) (850mg orally twice a day) for 12 cycles.
SECONDARY OBJECTIVES:
I. To determine the effect of metformin on breast tissue density of overweight or obese women at elevated risk for breast cancer using qualitative mammographic fat density criteria.
II. To determine the effect of metformin on the insulin axis in serum of overweight or obese women at elevated risk for breast cancer treated with metformin (850mg orally twice a day) for 12 cycles.
III. To determine the toxicities associated with metformin.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive metformin hydrochloride by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive placebo by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter. Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for up to 5 years.
Type d'étude
Inscription (Réel)
Phase
- Première phase 1
Contacts et emplacements
Lieux d'étude
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Indiana
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Indianapolis, Indiana, États-Unis, 46202
- Indiana University Melvin and Bren Simon Cancer Center
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Patients must be post-menopausal women; post-menopausal women are defined as: (1) those >= 50 years of age who had not menstruated during the preceding 12 months or who had castrate follicle-stimulating hormone levels (> 40 IU/L), (2) those who had undergone a bilateral oophorectomy
Patients must be at elevated risk for breast cancer based on strong family history or a history of breast biopsy documenting atypical hyperplasia anytime in the past; for this study strong family history is defined as having:
- 1 first-degree (parent, offspring, sibling) relative =< 50 years old when diagnosed with breast cancer, or
- >= 2 first-degree relatives of any age when diagnosed with breast cancer, or
- >= 2 second-degree (aunts, uncles, grandparents, grandchildren, nieces, nephews, or half-siblings) maternal or paternal relatives diagnosed with breast cancer and at least 1 diagnosed at =< 50 years of age
Patients must have a body mass index (BMI) >= 25.0 as calculated by the formula: weight in pounds / height squared x 703 = BMI; a BMI of:
- 18.5-24.9 is considered normal;
- 25.0-29.9 is considered overweight;
- 30.0+ is regarded as obese
- Patients must be willing to complete a bilateral mammogram at baseline with repeat exam after 12 cycles of protocol therapy; patients who have had a mammogram within 1 month prior to registration to protocol therapy will not need to repeat the exam
- Patients must be willing to provide a core tissue biopsy at baseline and with repeat tissue collection after 12 cycles of protocol therapy
- White blood cell (WBC) >= 3.0 x 109/L
- Granulocytes (polymorphs + bands) >= 1.5 x 109/L
- Platelets >= 100 x 109/L
- Hemoglobin >= 110 g/L
- Aspartate aminotransferase (AST) =< 1.8 X upper limit of normal (ULN)
- Alanine aminotransferase (ALT) =< 1.8 X ULN
- Alkaline phosphatase =< 2 X ULN
- Serum creatinine =< 115 umol/L (1.3mg/dL)
- Serum bilirubin =< institution ULN (except for subjects with Gilbert's Disease who are eligible despite elevated serum bilirubin level)
- 12 hour fasting glucose level < 7.0 mmol/L
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1 within 28 days of registration
- Life expectancy of >= 5 years
- Subjects must be accessible for treatment, adverse event tracking and follow-up as determined by the treating physician
- Subject consent and authorization for the release of health information must be obtained according to local institutional guidelines
Exclusion Criteria:
- No history of any malignancy except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for >= 5 years
- No known diabetes (type 1 or 2) or baseline fasting glucose >= 7.0 mmol/L
- No known hypersensitivity or intolerance to metformin
- No condition associated with increased risk of metformin-associated lactic acidosis (e.g. congestive heart failure defined as New York Heart Association [NYHA] class III or IV functional status, history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day)
- No current treatment with metformin, sulfonylureas, thiazolidinediones or insulin for any reason
- No breastfeeding
- No concurrent or planned participation in randomized trials of weight loss or exercise interventions or trials targeting insulin, insulin-like growth factor 1 (IGF-1) or their receptors
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: Arm I (metformin hydrochloride)
Patients receive metformin hydrochloride by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter.
Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.
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Études corrélatives
Bon de commande donné
Autres noms:
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Comparateur placebo: Arm II (placebo)
Patients receive placebo by mouth once daily on days 1-30 in course 1 and twice daily on days 1-30 thereafter.
Treatment repeats every 30 days for 12 courses in the absence of disease progression or unacceptable toxicity.
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Études corrélatives
Bon de commande donné
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Changes in the phosphorylation of proteins after metformin exposure
Délai: Baseline and 12 months
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Reverse phase proteomic assays (RPPA) will be performed to measure changes in the phosphorylation of proteins after metformin exposure.
Changes in the phosphorylation of proteins after metformin exposure will be calculated and compared using two-sample t-tests.
As a supplemental analysis, analysis of covariance (ANCOVA) will be used to model the 12 month levels adjusted for baseline.
Assumptions for analysis will be checked and non-parametric methods used if needed; however it is expected that the data will be normally distributed on the log scale.
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Baseline and 12 months
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Changes in ordinal level of breast density
Délai: Baseline and 12 months
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Changes in ordinal level of breast density will be performed using the breast density criteria previously established by Boyd and colleagues (New England Journal of Medicine 2007).
Each image will be grouped into one of six categories: 0%, <10%, 10-25%, 25-50%, 50-75% and >75%.
Changes will be compared between the two groups using Wilcoxon Rank-Sum tests.
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Baseline and 12 months
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Proportion of patients experiencing adverse events assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Délai: Up to 30 days
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Will be tabulated by arm and grade.
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Up to 30 days
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Anna Maria Storniolo, MD, Indiana University Melvin and Bren Simon Cancer Center
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- IUCRO-0365
- NCI-2013-00422 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- 1301010355 (Autre identifiant: Indiana University IRB)
Informations sur les médicaments et les dispositifs, documents d'étude
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