Clinical trial NCT00462865 (phase 2, status: terminated)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: gemcitabine and capecitabine and avastin
SMILES: NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F
Reason stopped: 
    dsmb determined toxicity of regimen more than originally thought. slow accrual.
  
Eligibility criteria:

        Inclusion Criteria:

        General health

          -  Women Age >18.

          -  ECOG Performance status 0-1

          -  Life expectancy must be 3 months. Clinical stage

          -  Histologically or cytologically adenocarcinoma of breast

          -  Pre-operative stage II-III per AJCC 6th edition, based on baseline evaluation by
             clinical examination, breast imaging, and/or preoperative work-up.

          -  Evidence of residual invasive breast cancer or node positive disease following
             neoadjuvant chemotherapy.

        Prior Therapy

          -  Patients must have received primary (neoadjuvant) chemotherapy for local or
             locoregional breast cancer containing an anthracycline and a taxane.

          -  Patients must have completed definitive resection of primary tumor with adequate
             excision of gross disease.

          -  Patients must have residual invasive carcinoma in the breast and/or residual carcinoma
             in one or more regional nodes following preoperative chemotherapy.

        Adequate hematologic and metabolic parameters within four weeks of study entry defined as:

          -  Absolute neutrophil count ≥1,500/mm3 Platelets ≥ 150,000/mm3

          -  Total bilirubin ≤ 2.0 mg/dL

          -  Serum creatinine ≤ 2x upper limit of normal

          -  Serum calcium ≤1.5x upper normal limit Concurrent treatments

          -  Current use of anti-coagulants is allowed as long as patients have been on a stable
             dose for more than 2 weeks with stable INR.

          -  Chronic therapy with full dose aspirin up to 325 mg/day or standard non-steroidal
             anti-inflammatory agents is allowed.

        Informed consent

          -  Provision of signed informed consent.

        Exclusion Criteria:

        Prior therapy

          -  No prior gemcitabine, continuous infusion 5-FU, or oral fluoropyrimidine
             (capecitabine, UFT, S-1, 5-FU/eniluracil, etc.)

          -  No known hypersensitivity to capecitabine or prior unanticipated severe reaction to
             (capecitabine, UFT, S-1, 5-FU/eniluracil, etc.) therapy or known hypersensitivity to
             5-fluorouracil.

          -  No concurrent or prior endocrine therapy as adjuvant treatment.

          -  No prior breast radiation

          -  Current, recent (within 4 weeks of the first infusion of this study), or planned
             participation in another experimental drug study

          -  Stage IV breast cancer

          -  Patients must not have evidence of metastatic disease at enrollment. Women of
             child-bearing potential.

          -  Nonpregnant and nonlactating.

          -  Women of child-bearing potential must have a negative serum pregnancy test and must
             agree to an effective means of contraception during the entire study period.

        Concurrent medical conditions:

          -  No other active cancers, except non-melanoma skin cancers.

          -  No serious infection or other serious underlying medical condition that would
             otherwise impair their ability to receive protocol treatment.

          -  Patients with clinically significant medical or psychiatric problems which may
             interfere with treatment on study.

        Avastin-specific exclusions:

          -  Inadequately controlled hypertension (defined as systolic blood pressure 150 and/or
             diastolic blood pressure > 100 mmHg on antihypertensive medications)

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  Known CNS disease

          -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment or anticipation of need for major surgical procedure during
             the course of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to study enrollment

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+
             (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should
             undergo a 24 hour

          -  urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).

          -  Known hypersensitivity to any component of bevacizumab any history of stroke or
             transient ischemic attack at any time

          -  History of myocardial infarction or unstable angina within 12 months of study
             enrollment Inability to comply with study and/or follow-up procedures