Phase III to Evaluate Patient´s Preference of Subcutaneous Trastuzumab vs Intravenous in HER2+ Advanced Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab Injectable Solution; Trastuzumab Injectable Product; Trastuzumab Injection
Intervention description: Subcutaneous injection vial with a fixed dose of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) identical to that provided by the device. 3 weeks x 2 cycles.; Single injection device is provided and loaded with the mixture of trastuzumab (600mg) and recombinant human hyaluronidase (10.000U) and is ready for use. 3 weeks x 2 cycles; Powder for concentrate for solution for infusion. 1 cycle
Intervention MeSH terms: Trastuzumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Eligible patients, from the randomization and before starting subcutaneous trastuzumab (SC-t), received an additional intravenous (IV-t) cycle. After receiving this cycle, patients started the treatment with the study medication, SC-t at a fixed dose of 600 mg every 3 weeks (+3 days) for 4 cycles (2 administered from the injection of a vial in a syringe and 2 with the single-use injection device [SID]), being randomized 1:1 in two arms of treatment without washout period:
Arm A (1 cycle of IV-t followed by 2 cycles of SC-t with vial followed by 2 cycles of SC-t with SID)
Arm B (1 cycle of IV-t followed by 2 cycles of SC-t with SID followed by 2 cycles of SC-t with vial)
This is not a cross-over study.
Masking: None (Open Label)
Enrollment: 166.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Subcutaneous trastuzumab; Intravenous trastuzumab; HER2 positive; Advanced Breast Cancer

Summary:

      GEICAM/2012-07 is a study phase III, prospective, open, randomized, multicenter and national
      designed to assess patient preference for intravenous (IV) or subcutaneous (SC) of
      trastuzumab, and within the SC by the administration through the vial or device
      self-administration in patients with disseminated breast cancer HER2.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Woman, 18 years old or upper.

          -  Patient with advanced breast cancer with human epidermal growth factor receptor 2 (HER
             2) positive histologically confirmed. The criteria for positivity HER 2 are:

               1. immuno-histochemistry (IHC) 3+ (>10% of tumor cells with complete and intense
                  membrane staining)

               2. IHC 2+ with fluorescent in situ hybridization (FISH) / Chromogenic in situ
                  hybridization (CISH) / silver-enhanced in situ hybridization (SISH) + for HER 2
                  amplification (*)

               3. FISH / CISH / SISH + for HER 2 amplification (*) (*) Defined as the ratio of
                  copies of HER 2/neu and copies of centromere of chromosome 17 (CEP17)> 2.2, or a
                  number of copies of HER 2/neu> 6, as per local laboratory criteria.

          -  Patient receiving trastuzumab with or without chemotherapy or hormonal therapy for at
             least 4 months.

          -  No evidence of disease progression (clinical and / or radiological) for at least 4
             months before inclusion in the study and with a life expectancy of at least 3 months.

          -  Adequate performance status: Eastern Cooperative Oncology Group (ECOG) <2.

          -  Adequate bone marrow function, liver and kidney

          -  Proper cardiac function (LVEF within normal limits the center, measured by
             echocardiography or MUGA).

          -  The patient must have been informed of the study and must sign and date informed
             consent document for entry into the trial.

          -  The patient must be willing and able to comply with study procedures and be available
             to answer the study questionnaires.

        Exclusion Criteria:

          -  Patients with no advanced breast cancer.

          -  Breast cancer patients with tumors HER 2-negative.

          -  The patient has another active malignancy other than breast adenocarcinoma; are
             excluded the non-melanoma skin cancer or any other properly treated in situ neoplasia.
             Patients with a history of malignancy, if they bear> 5 years without evidence of
             disease could be included.

          -  The patient has uncontrolled brain metastases.

          -  Concomitant administration, or in the 4 weeks prior to study entry, of other
             experimental treatment.

          -  Known hypersensitivity to trastuzumab or to any of its components.

          -  Patients with severe dyspnea at rest or requiring supplemental oxygen.

          -  Heart disease or serious medical pathological prevent trastuzumab administration:
             documented history of congestive cardiac insufficiency (CCI), high-risk arrhythmias
             uncontrolled angina requiring medication, clinically significant valvular disease,
             history of myocardial infarction or evidence of transmural infarction on ECG or
             hypertension poorly controlled.

          -  Presence of any concomitant serious systemic disease that is incompatible with the
             study (at the discretion of the investigator).

          -  The patient is pregnant or lactating. Women of childbearing potential should undergo
             pregnancy testing blood or urine within 14 days prior to inclusion as institutional
             rules and use a non-hormonal contraceptive suitable: intrauterine device, barrier
             method (condom or diaphragm) also used in conjunction with spermicidal cream, total
             abstinence or surgical sterilization, during treatment with the study drugs and for 6
             months following the end of treatment.