Breast Cancer With Low Risk Of Local Recurrence: Partial and Accelerated Radiation With Three-Dimensional Conformal Radiotherapy (3DCRT) Vs. Standard Radiotherapy After Conserving Surgery (Phase III Study
Condition: Breast Cancer
MeSH terms: Breast Neoplasms; Recurrence
Study type: Interventional

Summary: 
      This study was designed and developed in the Emilia Romania research and innovation program
      (PRI ER). The study does not have commercial sponsors and comes under the independent studies
      provided for by Ministerial Decree 17.12.2005. The PRI ER program will guarantee a
      contribution to the study for the first three years of recruitment through the regional
      Innovation Fund, to cover the costs of coordination and data management sustained by the
      Coordinating Center.

      Primary Objectives The study proposes to evaluate whether partial hypofractionated and
      accelerated irradiation of the sole surgical cavity, in patients suffering from breast cancer
      with low risk of local recurrence and who undergo conservative surgery, is not inferior to
      postoperative irradiation with conventional fractionation of the entire breast as regards
      local control (incidence of ipsilateral recurrences as prime event).

      Secondary Objectives Comparison of the global survivals, freedom from locoregional
      recurrences (with exception for contralateral tumors and second tumors), distant relapse-free
      (except for local or regional relapses or in the contralateral breast) in patients treated
      with conventional radiotherapy and accelerated partial radiation.

      To evaluate whether accelerated partial irradiation offers cosmetic results, acute toxicity
      comparable with conventional irradiation.

      Possible connection with other national and international studies Similar studies which
      nonetheless evaluate different methods of partial irradiation are currently underway.

      Study Design Multicenter phase III controlled randomized, unblinded study of non-inferiority.

      Number of cases Recruitment of 3302 patients is planned. Target Population of the Study Women
      aged = > 49, ECOG 0-2, undergoing conservative breast surgery for invasive breast cancer, pT
      1-2 (< 3 cm in diameter) pN0-N1 M0, unifocal, resection margins histologically negative (³ 2
      mm) at first intervention or after subsequent widening.

      Duration of the recruitment and of the subsequent follow-up A recruitment of 8 years is
      planned and a follow-up period of 5 years for an overall duration of the study of 13 years.

      Treatment

      The patients will be randomized to receive one of the following treatments:

      Trial arm 38.5 Gy total in 10 fractions (3.85 Gy per fraction), twice a day with an interval
      of at least 6 hours between the two fractions, for five consecutive working days.

      Control arm 50.0 Gy in 25 fractions (2 Gy per fraction), once a day for 5 days in the week.

      Endpoints Primary: survival free of local ipsilateral recurrence as prime event Secondary:
      global survival, locoregional recurrence-free, distant recurrence-free, acute and late
      toxicity (RTOG) and cosmetic result.

      Evaluation and Follow-Up Program Controls are planned during the radiotherapy, at the end of
      treatment, at 6 weeks, 3-6-12 months from the end of the radiotherapy and then once a year
      until the end of 5 years.

      Data Analysis Partial irradiation will be considered not inferior to the standard irradiation
      if the top extreme of the HR confidence interval at 95% (to endpoint) does not exceed the
      established value of 1.5 The study was sized in relation to the rate of local ipsilateral
      breast recurrences as prime event at 5 years and assuming that this rate in the standard
      treatment group is 4%, accepting as maximum Hazard Ratio inferior to 1.5 and error a and b
      equal respectively to 0.05 and 0.10 and test at an endpoint.

      The survivals will be calculated using the Kaplan-Meier method. The hazard ratio (HR) will be
      calculated using the Cox model and its confidence interval at 95% will be reported.

      Ethical Aspects and Informed Consent For participation in the study an informed consent is
      planned appropriately drawn up and submitted to the approval of the Ethics Committees.

      The clinical study will be carried out according to the ethical principles of the Helsinki
      Declaration, the GCP guidelines, the Italian laws and regulatory activities for carrying out
      clinical studies.

      Before formal commencement of the study its approval/sole opinion by the reference Ethics
      Committee of the proposing group is stipulated. The individual investigators of the different
      participating institutions are directly responsible for the submission for approval of the
      protocol by their Ethics Committees.
    


Intervention name(s): partial breast irradiation; whole breast irradiation
Intervention type(s): Radiation; Radiation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment