Clinical Trials

Inclusion Criteria:

Patients must have histologically confirmed adenocarcinoma of the breast at significant risk of distant recurrence based on at least one of the following criteria:

For Axillary Lymph Node Positive Disease

• Involvement of at least one sentinel or axillary lymph node on routine histologic examination. Patients with negative sentinel nodes and negative axillary nodes or involvement only demonstrated by immunohistochemistry are not eligible unless they meet one of the other eligibility criteria below.
  • NOTE: Consider intramammary nodes as equivalent to axillary nodes for the purposes of eligibility and stratification.

For Axillary Lymph Node Negative Disease

• ER negative tumor > 1 cm.
• ER+ tumor > 5 cm regardless of recurrence score.
• ER+ tumor >1 cm but < 5 cm with a recurrence score > 11. (Patients enrolled in the TAILORx trial are eligible).
• Date of histological confirmation of adenocarcinoma of the breast at significant risk of distant recurrence__________.
  • NOTE: Axillary dissection is strongly encouraged in patients with lymph node involvement identified on sentinel node biopsy.
  • NOTE: Premenopausal patients with ER+ tumor may participate in the IBCSG SOFT trial.
  • NOTE: Premenopausal patients with ER- tumor may participate in S0230.
• Patients must have completed definitive breast surgery including total mastectomy and axillary dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy, breast conservation surgery and axillary dissection or breast conservation surgery and sentinel node biopsy.
  • NOTE: Breast conservation surgery includes lumpectomy, partial mastectomy, and excisional biopsy.
• Margins of breast conservation surgery or mastectomy must be histologically free of invasive breast cancer and ductal carcinoma in situ (DCIS). Patients with resection margins positive for lobular carcinoma in situ (LCIS) are eligible.
• Time from last surgery for breast cancer (breast conservation surgery, mastectomy, sentinel node biopsy, axillary dissection or re-excision of breast conservation surgery margins) to planned treatment start date must be > 28 days and < 84 days.
• Date of last surgery: __________
• Scheduled Day 1 of protocol treatment: _________
  • NOTE: Treatment start date more than 84 days or < 28 days from date of last surgery is considered a protocol violation.
• ECOG performance status of 0-1
• Patients must have adequate organ function within < 8 weeks prior to randomization, as measured by:
  • Absolute neutrophil count > 1000/mm^3
    • Absolute neutrophil count:________
    • Date of Test: ____________
  • Platelet count > 100,000/mm^3
    • Platelet count:____________________
    • Date of Test: ____________
  • Total bilirubin < 1.5 mg/dL
    • Total bilirubin:____________________
    • Date of Test: ____________
  • AST < 2 X upper limit of normal
    • AST:________________
    • Date of Test: ____________
    • Upper Limit of Normal: ______________
  • Serum creatinine < 1.5 mg/dL
    • Serum Creatinine:___________
    • Date of Test: ____________
  • Urine protein: creatinine (UPC) ratio < 1.0* or 24-hour protein
    • Urine protein: creatinine ratio:________ or 24-hour protein: ________
    • Date of Test: ____________
  • PTT < 1.5 X ULN
    • PTT: _______________
    • Date of Test: ____________
    • Normal: _______________
  • LVEF > institutional limits of normal by MUGA or ECHO
    • LVEF: ______________
    • Date of Test: ____________
    • Institutional limit of normal: _______________

* Please see Appendix V for instructions on how to obtain the urine protein: creatinine ratio.

• Patients who have undergone breast conservation surgery must receive radiation. Prior to randomization, the investigator must specify the planned radiation technique.
  • _____ Whole breast radiation (WBRT) after chemotherapy
  • _____ Accelerated partial breast radiation (APBI) after chemotherapy
  • _____ Accelerated partial breast radiation (APBI) prior to chemotherapy
  • NOTE: If APBI was completed prior to study entry, day 1 of protocol therapy must be at least 4 weeks after the completion of APBI.
  • Last day of APBI __________ Planned day 1 of protocol therapy ________
• Post-mastectomy RT is required for all patients with a primary tumor of > 5 cm or involvement of 4 or more lymph nodes. Post-mastectomy RT may be administered at the investigator’s discretion for all other mastectomy patients.
  • Is post-mastectomy radiation planned? Yes/No________
• Patients with HER2 + (3+ by IHC or FISH ratio > 2) breast cancer are not eligible.
• Patients with synchronous bilateral breast cancer (diagnosed within one month) are eligible if the higher TNM stage tumor meets the eligibility criteria for this trial.
• Patients must not have clinical evidence of inflammatory disease or fixed axillary nodes at diagnosis.
• Patients must not have received prior cytotoxic chemotherapy or hormonal therapy for this breast cancer. Prior treatment with an anthracycline, anthracenedione or taxane for any condition is not allowed.
  • NOTE: Prior use of tamoxifen for chemoprevention is allowed but must be discontinued at study entry. Similarly, prior raloxifene use is allowed but must be discontinued at study entry.
• Patients must not have had any major surgical procedure within 28 days of planned treatment start date.
• Date of last major surgery __________ Scheduled day 1 of protocol treatment __________
  • NOTE: Non-operative biopsy or placement of a vascular access device is not considered a major surgery.
• Patients may not have had placement of a vascular access device within 24 hours of planned Day 1 of treatment.
  • Is an indwelling vascular device planned? Yes/No____________
  • If yes, date of vascular device placement____________
  • Scheduled Day 1 of treatment________________
• Patients must not have clinically significant cardiovascular or cerebrovascular disease, including:
• Any history of:
  • Cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage;
  • Ischemic bowel;
• Within the last 12 months:
  • Myocardial infarction;
  • Unstable angina;
  • New York Heart Association (NYHA) class II or greater congestive heart failure;
  • Grade II or greater peripheral vascular disease;
  • NOTE: See Appendix X for NYHA classification and peripheral vascular disease grading criteria.
• Active at study entry:
  • Uncontrolled hypertension defined as SBP > 160 or DBP > 90;
  • Uncontrolled or clinically significant arrhythmia.
  • NOTE: Blood pressure must be obtained within < 8 weeks prior to randomization.
  • NOTE: Patients with controlled atrial fibrillation are eligible.
• Patients who require full dose anticoagulation may enroll provided they meet the following criteria:
  • the patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or be on stable dose of LMW heparin;
  • the patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. varices)
  • NOTE: Prophylactic use of anticoagulants to maintain patency of a vascular access device is permitted.
• Patients must not have a bleeding diathesis, hereditary or acquired bleeding disorder or coagulopathy.
• Patients must not have a non-healing wound or fracture. Patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization are not eligible.
• Patients must not have hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies.
• Male or female patients age > 18 years of age are eligible.
• Women must not be pregnant or breast-feeding due to the potential harmful effects of bevacizumab on the developing fetus. All females of childbearing potential must have a blood or urine test within 7 days prior to randomization to rule out pregnancy.
  • Is patient a woman of child-bearing potential?________ (Yes/No)
  • If yes, date of blood or urine test: ____________
  • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception.
• STEP 2: Unblinding and Re-registration to Arm D
• Only Step I patients treated on Arm C who have not ended treatment are eligible to register to Step 2, Arm D.
• Step 3: Registration to Ancillary Study EL112LAB
  • All patients who meet the following criteria are eligible to participate in the ancillary study:
  • Patient was registered to Step 1 (Arms A, B, or C) at least 4.5 years (54 months) and no more than 7.5 years (90 months) prior to registration to Step 3. It is preferable for patients to be registered to Step 3 at 5 years (60 months +/- 6 months) after registration to Step 1.
  • Patient is disease free, with no prior recurrence, at time of registration to Step 3.
  • Primary tumor tissue (FFPE) if not previously submitted after randomization on Step 1 as outlined in Section 10 must be available for submission within 4 weeks following registration to Step 3.

Eligibility last updated 10/12/22. Questions regarding updates should be directed to the study team contact.