Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab With or Without Trastuzumab for Adjuvant Treatment of Patients With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Doxorubicin and cyclophosphamide (AC) + bevacizumab; Docetaxel (T) + bevacizumab; Docetaxel, doxorubicin, cyclophosphamide (TAC) + bevacizumab; Docetaxel, carboplatin, trastuzumab (TCH) + bevacizumab; Bevacizumab and trastuzumab maintenance therapy; Bevacizumab maintenance therapy
Intervention description: For every 3-week cycle
bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
doxorubicin 60 mg/m^2 IV push or infusion followed by cyclophosphamide 600 mg/m^2 IV push or infusion
Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy; For every 3-week cycle
bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
docetaxel 100 mg/m^2 IV
Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy
Note: The starting dose of docetaxel was reduced to 75 mg/m^2 if toxicity occurred that met the criteria for doxorubicin dose reduction; For every 3-week cycle
bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
doxorubicin 50 mg/m^2 IV push or infusion followed by cyclophosphamide 500 mg/m^2 IV push or infusion followed by docetaxel 75 mg/m^2
Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy; For every 3-week cycle
bevacizumab 15 mg/kg infused intravenously (IV) on Day 1 followed by
docetaxel in 75 mg/m^2 IV followed by carboplatin AUC 6 mg/mL/min IV followed by
trastuzumab 6 mg/kg by IV infusion (For the first cycle 1 only a loading dose of trastuzumab 8 mg/kg IV was infused on Day 2)
Prophylactic G-CSF was administered within 24 hours following each cycle of chemotherapy but no greater than 72 hours after chemotherapy; bevacizumab 15 mg/kg was infused IV followed by
trastuzumab 6 mg/kg IV
Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.; - bevacizumab 15 mg/kg was infused IV
Treatment was every 3 weeks for 52 weeks from the date of the first administration regardless of the number of doses received or missed.
Intervention MeSH terms: Cyclophosphamide; Bevacizumab; Carboplatin; Docetaxel; Doxorubicin; Liposomal doxorubicin; Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 214.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase IIb, randomized, parallel-group, noncomparative, multicenter, pilot study
      designed to evaluate the safety and efficacy of bevacizumab with or without (+/-) trastuzumab
      administered with three different docetaxel-based combination regimens for the adjuvant
      treatment of participants with node positive or high-risk node negative breast cancer.
    

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:

          -  Women >/= 18 years of age.

          -  Histologically proven breast cancer with an interval between definitive breast surgery
             that includes axillary lymph node (LN) dissection or axillary nodal evaluation and
             study registration of < 60 days. (Note: Cycle 1 of chemotherapy treatment may NOT be
             infused until > 28 days after the date of definitive breast surgery and the
             participant must be recovered from any clinically significant toxicity thereof.)

          -  Definitive surgical treatment must be either mastectomy, or breast conserving surgery
             with axillary lymph node dissection (axillary lymph node evaluation can be either full
             axillary node dissection or sentinel LN evaluation followed by dissection if sentinel
             LN is positive) for operable breast cancer (pT1-4 [including inflammatory], pNO-3, and
             MO). Margins of resected specimen from definitive surgery must be histologically free
             of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma
             in-situ does not count as a positive margin.

          -  Subjects must be either lymph node-positive (pN1-3) or lymph node-negative (pN0) with
             high-risk features as determined by Investigator.

          -  High-risk, lymph node-negative participants, (pN0) will be defined as subjects having
             invasive adenocarcinoma with either a negative sentinel node biopsy (pN0[sn]) OR
             negative lymph node dissection (pN0) disease AND tumor size > 2 cm or tumor size >/= 1
             cm with at least one of the following factors:

               -  negative estrogen receptor (ER) and negative progesterone receptor (PR) status

               -  histologic and/or nuclear Grade 2-3; or

               -  age < 35 years

          -  HER2/neu positive or negative tumors are eligible. HER2 positivity must be documented
             by fluorescence in situ hybridization (FISH).

          -  Estrogen and progesterone receptor status must be performed on the primary tumor prior
             to study entry. Results must be pending or known at the time of study entry.

          -  Normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF)
             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.

          -  Hematology evaluation within 2 weeks prior to study entry:

               -  Absolute neutrophil count (ANC) >/= 1,500/μL

               -  Platelets >/= 100,000/μL

               -  Hemoglobin >/= 9 g/dL

          -  Hepatic function evaluation within 2 weeks prior to study entry:

               -  Total bilirubin </= ULN for the institution

               -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be in
                  the acceptable range.

          -  Complete staging work-up as follows: All subjects must have an appropriate
             radiographic evaluation, e.g., computed tomography (CT), positron emission tomography
             (PET)/CT, and/or (magnetic resonance imaging) MRI of the brain, chest, abdomen and
             pelvis, and imaging of bone by either a bone scan or PET scan. In cases of positive
             bone imaging, a bone X-ray or MRI evaluation is mandatory to rule out the possibility
             of metastatic bone scan disease. Other tests may be performed as clinically indicated.
             It is recommended that all baseline staging should be completed within 35 days prior
             to study entry.

        Exclusion Criteria:

          -  Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy,
             chemotherapy).

          -  Prior anthracycline therapy, taxoids or platinum salts for any malignancy.

          -  Prior radiation therapy for breast cancer or any radiotherapy to the chest wall for
             any other malignancy.

          -  Bilateral invasive breast cancer.

          -  Pregnant or lactating subjects

          -  Cardiac disease or risk for same as judged by Investigator

          -  Other serious illness or medical conditions such as (partial list- review with
             Investigator) history of significant neurologic or psychiatric disorders that would
             prohibit the understanding and giving of informed consent, active uncontrolled
             infection, active peptic ulcer, unstable diabetes mellitus or subjects with
             symptomatic, intrinsic lung disease resulting in dyspnea at rest

          -  Current therapy with any hormonal agent such as raloxifene, tamoxifen, or other
             selective estrogen receptor modulators (SERMs), either for osteoporosis or prevention
             of breast cancer. Subjects must have discontinued these agents prior to study entry.

          -  Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment must
             be stopped prior to study entry.

          -  Concurrent treatment with other experimental drugs. Participation in another clinical
             trial with any investigational non-marketed drug within 30 days prior to study entry.

          -  Concurrent treatment with any other anti-cancer therapy.

          -  Male subjects, as no clinical efficacy or safety data are available from phase I-II
             studies.

          -  Chemotherapy and/or bevacizumab may not be given until > 7 days following a minor
             surgical procedure. Chemotherapy may be given without bevacizumab in circumstances in
             which the participant has recovered sufficiently to receive chemotherapy but has not
             yet reached a 28 day time point at which bevacizumab could be administered.