Myocet + Cyclophosphamide + Metformin Vs Myocet + Cyclophosphamide in 1st Line Treatment of HER2 Neg. Metastatic Breast Cancer Patients
Condition: Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a phase II comparative randomized clinical trial.

      Eligible patients will be randomized (1:1) to:

      Arm A: Myocet plus Cyclofosfamide plus Metformin Arm B: Myocet plus Cyclofosfamide

      Statistical Considerations:

      In this randomized phase II study, the sample size was calculated basing on the primary
      end-point (PFS) and assuming an error α = 10% (2-tailed) with a power of 80%.

      To find an advantage of 4 months of median time to progression (6 months in the control arm B
      and 10 months in the experimental arm A) will be recruited 112 patients (98 events) for a
      period of 24 months and will be considered further 12-month of follow-up. The primary
      analysis of the study will be conducted in accordance with the "intention to treat"
      principle, the secondary analysis will be conducted in the "per protocol" population.
    

Detailed description: 
      MULTICENTER, RANDOMIZED, COMPARATIVE STUDY OF MYOCET PLUS CYCLOPHOSPHAMIDE PLUS METFORMIN
      VERSUS MYOCET PLUS CYCLOPHOSPHAMIDE IN FIRST LINE TREATMENT OF HER2 NEGATIVE METASTATIC
      BREAST CANCER PATIENTS.

      The aim of this study is to determine if the addition of metformin to the regime Myocet /
      Cyclophosphamide improves disease-free survival in patients with HER2-negative metastatic
      breast cancer.

      The primary objective is the evaluation of the clinical efficacy of the combination of Myocet
      / Cyclophosphamide plus Metformin compared to treatment with only Myocet / Cyclophosphamide,
      in terms of progression-free survival (PFS).

      Clinical secondary objectives are:

        -  Objective response rate

        -  Overall survival

        -  Tolerability

        -  Progression-free survival, objective response rate and overall survival according to
           Homa Index levels.

      Secondary biological endpoint is the characterization of the metabolic profile of patients
      (sensitivity in insulin levels).

      Treatment Arm A (experimental treatment):

      Metformin 1000 mg, 2 times daily per os*. Myocet 60 mg/m2, intravenous infusion, on day 1,
      every 21 days Cyclophosphamide 600 mg/m2, intravenous infusion, at day 1 every 21 days.

      * During cycle 1, patients will assume only metformin from day 1 to day 13 and will begin
      chemotherapy from day 14. From day 1 to day 3, patients will assume Metformin 1000 mg once a
      day. Starting from day 4 patients will assume Metformin 1000 mg 2 times a day.

      Arm B (standard treatment):

      Myocet 60 mg/m2, intravenous infusion, on day 1, every 21 days Cyclophosphamide 600 mg/m2,
      intravenous infusion, on day 1, every 21 days

      Chemotherapy will be performed for 8 cycles.

      The treatment will be continued until progression of disease.

      Statistical Considerations:

      In this randomized phase II study, the sample size was calculated basing on the primary
      end-point (PFS) and assuming an error α = 10% (2-tailed) with a power of 80%.

      To find an advantage of 4 months of median time to progression (6 months in the control arm B
      and 10 months in the experimental arm A) will be recruited 112 patients (98 events) for a
      period of 24 months and will be considered further 12-month of follow-up. The primary
      analysis of the study will be conducted in accordance with the "intention to treat"
      principle, the secondary analysis will be conducted in the "per protocol" population.
    

Intervention name(s): Metformin + Myocet + Cyclophosphamide; Myocet + Cyclophosphamide
Intervention type(s): Drug; Drug
Intervention description(s): Metformin + Myocet + Cyclophosphamide:
Metformin 1000 mg, 2 times daily per os*. Myocet 60 mg/m2, intravenous infusion, on day 1, every 21 days Chemotherapy will be performed for 8 cycles Cyclophosphamide 600 mg/m2, intravenous infusion, at day 1 every 21 days.
* During cycle 1, patients will assume only metformin from day 1 to day 13 and will begin chemotherapy from day 14. From day 1 to day 3, patients will assume Metformin 1000 mg once a day. Starting from day 4 patients will assume Metformin 1000 mg 2 times a day.; Myocet + Cyclophosphamide:
Myocet 60 mg/m2, intravenous infusion, on day 1, every 21 days Cyclophosphamide 600 mg/m2, intravenous infusion, on day 1, every 21 days Chemotherapy will be performed for 8 cycles
Other intervention name(s): metformin; myocet; cyclofosfamide; myocet; cyclofosfamide
Intervention MeSH terms: Metformin; Cyclophosphamide; Doxorubicin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HER2 negative; metastatic breast cancer; non endocrine responsive disease