Pilot Study of Docetaxel & Bevacizumab +/- Trastuzumab in First-Line Treatment of Patients With Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Bevacizumab; Docetaxel; Trastuzumab
Intervention description: Bevacizumab (Avastin) 15 mg/kg will be administered prior to chemotherapy on
On Day 1 of the 1st cycle over 120 minutes
On Day 1 of the 2nd cycle over 90 minutes, if no reaction on the first dose
On Day 1 of 3rd cycle over 60 minutes, if no reaction on previous doses
On Day 1 of subsequent cycles over 30 minutes, if no reaction on previous doses; Docetaxel 75 mg/m^2 IV infused over 60 minutes after completion of Bevacizumab infusion q3w; A loading dose of 8 mg/kg Trastuzumab (Herceptin) IV will be infused over 90 minutes on Day 2 of Cycle 1.
For all subsequent cycles 6 mg/kg trastuzumab will be administered on Day 1 one hour following completion of docetaxel infusion
Intervention MeSH terms: Bevacizumab; Trastuzumab; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 73.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Pilot, phase II, parallel-group, open-label, noncomparative, prospective, multicenter study
      designed to evaluate the progression-free survival of docetaxel and bevacizumab ± trastuzumab
      for the first-line treatment of participants with metastatic breast cancer. Participants were
      stratified according to human epidermal growth factor receptor-2 (HER2) status at the time of
      enrollment. HER2 negative participants were assigned to receive docetaxel and bevacizumab
      (DB). HER2 positive participants were assigned to receive docetaxel, bevacizumab, and
      trastuzumab (DBT).

      All participants (except one) were off study treatment on 30 June 2011. All efficacy analysis
      and safety analysis was performed using the cut-off date of June 2011. One participant
      continued treatment till 11 March 2012. For this participant, adverse events were collected
      upto 19 April 2012 and included in the safety analysis.
    

Eligibility criteria:

        The following information on clinical trials is provided for information purposes only to
        allow participants and physicians to have an initial discussion about the trial. This
        information is not intended to be complete information about the trial, to contain all
        considerations that may be relevant to potential participation in the trial, or to replace
        the advice of a personal physician or health professional.

        INCLUSION CRITERIA:

          1. Histologically or cytologically proven adenocarcinoma of the breast at first diagnosis

          2. Stage IV disease with at least one measurable lesion according to the RECIST criteria

          3. HER2/neu positive as determined by 3+ immunohistochemistry (IHC) staining or
             fluorescence in situ hybridization (FISH) positivity or negative tumors

          4. Life expectancy of >/= 24 weeks

          5. No prior chemotherapy for metastatic breast cancer. (Prior endocrine therapy is
             permitted).

          6. Prior neoadjuvant or adjuvant chemotherapy is permitted, or at least 12 months must
             have elapsed since the neoadjuvant or adjuvant therapy. Subjects may have received
             prior adjuvant anthracyclines (maximum cumulative dose, 360 mg/m^2 doxorubicin or 750
             mg/m^2 epirubicin)

          7. At least 4 weeks since prior surgery, radiotherapy, endocrine therapy, or experimental
             drug therapy with complete recovery from the effects of these interventions

          8. It is recommended that all baseline staging should be completed within 35 days prior
             to study entry. All subjects will have the following workup as applicable; CT scan of
             brain, CT scan or MRI of chest and abdomen, and bone scan or PET scan. In cases of
             positive bone or PET scans, bone X-ray evaluation and/or MRI is required to confirm or
             exclude metastatic bone disease. Subjects with metastatic disease limited to bone are
             ineligible unless at least one lytic lesion is measurable and can be followed by
             RECIST criteria. Other tests may be performed as clinically indicated

          9. Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF)
             of >/= 50% or shortening fraction (multiple-gated acquisition [MUGA] scan or
             echocardiography respectively). The result must be greater than the lower limit of
             normal (LLN) for the institution.

         10. Subjects receiving bisphosphonate therapy; however, if bisphosphonates were started
             within <2 months prior to treatment the bone lesions will not be evaluated for
             response, and the subjects must have another site of metastatic disease that is either
             measurable or evaluable for response

        EXCLUSION CRITERIA:

          1. Prior chemotherapy for metastatic breast cancer

          2. Prior treatment with bevacizumab or other anti-VEGF therapy

          3. Concurrent treatment with any other non-protocol anticancer therapy with the exception
             of radiation therapy as long as all target lesions being followed are not in the
             radiation field and if HER2/neu positive, HER2/neu-directed therapy

          4. Current or prior history of brain or leptomeningeal metastases

          5. Presence of neuropathy >/= 2

          6. Presence of any non-healing wound, fracture, or ulcer, or the presence of clinically
             significant (>/= Grade 2) peripheral vascular disease

          7. History of any other malignancy within the past 5 years, with the exception of
             non-melanoma skin cancer or carcinoma in-situ of the cervix

          8. Clinically significant cardiovascular disease

          9. Active peptic ulcer disease, inflammatory bowel disease, or other gastrointestinal
             condition increasing the risk of perforation; history of abdominal fistula,
             gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to
             beginning therapy

         10. History of bleeding diathesis or coagulopathy