A Study of Liposomal Doxorubicin + Docetaxel + Trastuzumab + Metformin in Operable and Locally Advanced HER2 Positive Breast Cancer
Condition: HER-2 Positive Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      It is a multicenter, open-label, two stage phase II trial, to assess activity, safety and
      potential early predictors of response in neoadjuvant setting. Patients with operable breast
      cancer (T1c and cytologically N1-2, or cT2-3, N0-N2, M0) or locally advanced breast cancer
      (T4a-d, N0-N2, M0) with overexpression or amplification of HER2 (AJCC 7th edition 2010) are
      included in the study.

      The primary objective is to evaluate the pathological complete response rate (pCR).

      The secondary objectives are:

        -  to evaluate the clinical response rate (RR).

        -  to evaluate the feasibility and systemic tolerance, with particular attention to cardiac
           toxicity.

        -  to evaluate the conservative surgery rate.

      Total duration of the trial is 36 months; planned treatment are 6 cycles of chemotherapy. At
      every cycle (every 21 days) will be administered:

      Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9:
      Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first
      infusion loading dose, then 2 mg/kg/week for subsequent injections. Day -13 to 0: Metformin
      is administered as single agent. From day -13 to day -11, Metformin 1000 mg will be
      administered once a day; from day -10 Metformin 1000 mg will be administered twice a day
      continuously until end of the study treatment.
    

Detailed description: 
      Multi-center, open-label phase II trial to assess activity of this chemotherapy scheme
      evaluated by pathologic complete response rate (pCR).

      Planned treatment are 6 cycles of chemotherapy.

      At every cycle (every 21 days) will be administered:

      Day 1: Liposome-encapsulated doxorubicin, 50 mg/m2 IV 1 hour infusion; Day 2 and 9:
      Docetaxel, 30 mg/m2 IV 1 hour infusion; Day 2, 9 and 16: Trastuzumab 4 mg/kg for the first
      infusion loading dose, then 2 mg/kg/week for subsequent injections Day -13 to 0: Metformin is
      administered as single agent. From day -13 to day -11, Metformin 1000 mg will be administered
      once a day; from day -10 Metformin 1000 mg will be administered twice a day continuously
      until end of the study treatment.

      Total duration of the trial: 36 months Enrollment period: 24 months Treatment: maximum of 6
      cycles (5 months) per patient Follow-up for recurrence: every six months for 5 years, than
      once a year until 10 years after surgery.It's necessary to recruit 46 patients for clinical
      objectives evaluation.
    

Intervention name(s): Liposomal doxorubicin; Docetaxel; Trastuzumab; Metformin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 50 mg/m2 by intravenous infusion over a period of 1 hour on day 1 of each cycle repeated every 21 days. A final concentration of between 0.4 to 1.2 mg/ml doxorubicin hydrochloride, is required; 30 mg/m2 by intravenous infusion over a period of 1 hour on day 2 and 9, every 3 week.They will be given for 6 cycles.; 4 mg/kg for the first administration (day 2 cycle 1) and 2 mg/kg for subsequent administrations. Trastuzumab will be given weekly for the duration of chemotherapy (day 2, 9, 16), then will be administered at the dose of 6 mg/Kg every 3 weeks until completion of 52 weeks of treatment.; It is administered as single agent from day -13 to 0. From day -13 to day -11, Metformin 1000 mg will be administered once a day; from day -10, Metformin 1000 mg will be administered twice a day continuously until end of the study treatment.
Other intervention name(s): Myocet®; taxotere; herceptin
Intervention MeSH terms: Metformin; Docetaxel; Doxorubicin; Liposomal doxorubicin; Trastuzumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HER-2 Positive Breast Cancer; operable breast cancer; locally advanced breast cancer; no prior therapy; pCR