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Pilot Evaluation of Bevacizumab, in Combination With Docetaxel and Cyclophosphamide in the Adjuvant Treatment of Patients With HER 2 Negative Breast Cancer

18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Pilot Evaluation of Bevacizumab, in Combination With Docetaxel and Cyclophosphamide in the Adjuvant Treatment of Patients With HER 2 Negative Breast Cancer



- Assess the feasibility of the combination of adjuvant bevacizumab, docetaxel, and
cyclophosphamide in patients with early-stage HER2-negative high-risk breast cancer.

- Determine the safety of this regimen with regards to cardiac toxicity, hypertension,
and bleeding complications in these patients.


- Evaluate the efficacy of this regimen by measuring Topo II overexpression in these

OUTLINE: This is a multicenter study.

Patients will receive 4 cycles of Docetaxel 75mg/m2 + 4 cycles of Cyclophosphamide 600mg/m2
(each cycle lasts 21 days) (+/- 3 days if a due date could not be met because of public
holidays, etc) and concomitant Avastin (Bevacizumab) 15mg/kg q 3weeks for treatment duration
of one year.

Bevacizumab at a dose of 15mg/kg will be administered as an intravenous infusion every 3
weeks for a treatment period of one year, regardless of missed doses.

Patients will be followed up through 5 years (i.e. from the time of registration through to
end of Year 5/ 1 year treatment and 4 years follow up).

Inclusion Criteria:

1. The patient must have histologically confirmed, invasive adenocarcinoma of the breast

-Involvement of at least one axillary lymph node on routine histologic examination.


- ER negative tumour >2 cm invasive cancer or

- ER positive tumour > 3cm invasive cancer. Note : Pre-menopausal patients with ER
positive tumour may participate in the International Breast Cancer Study Group
(IBCSG) SOFT study. High risk and registered and intermediate risk and
randomized for chemotherapy patients enrolled in the TAILOR x study may
participate in this study (once prior approval from IBCSG and ECOG is received)

2. Patients must have undergone standard surgical treatment for their breast cancer,
consisting either of mastectomy or a standard breast-conserving operation, which
included appropriate axillary surgery. Such axillary procedures will include either
sentinel node biopsy or an axillary dissection.

3. Patients must have disease which is HER2 negative (0, or 1+ by immunohistochemistry
(IHC) or fluorescence in situ hybridization FISH non amplified)

4. Patients must have negative evaluations for metastatic disease, including chest x-ray
or CT scan, isotope bone scan, and either computed tomography (CT), MRI or ultrasound
of the liver. Position emission tomography (PET) scan would also suffice in place of
the above tests (unless a bone scan is clinically indicated) within 3 months prior to

5. Patients must have a normal cardiac ejection fraction by echocardiogram (ECHO) or
multigated acquisition (MUGA) scan within 3 months prior to registration.

6. The electrocardiogram (ECG) performed within 3 months prior to registration must not
have any clinically significant abnormalities reported.

7. 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.

8. The interval between the last surgery for breast cancer (breast conservation surgery,
mastectomy, sentinel node biopsy, axillary dissection or re-excision of breast
conservation surgery margins) and Day 1 of treatment must be > 21 days and no more
than 84 days.

9. ECOG performance status of 0-1.

10. Patients must have adequate organ function within < 8 weeks prior to registration, as
measured by:

- Absolute neutrophil count > 1.2 x 10^9/L

- Platelet count > 100 x 10^9/L

- Normal bilirubin (except for patients with congenital hyperbilirubinemia)

- total bilirubin must be ≤ upper limit of normal (ULN) for the lab unless the
patient has a bilirubin elevation > ULN to 1.5 x ULN due to Gilberts disease or
similar syndrome involving slow conjugation of bilirubin

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2x ULN

- Serum creatinine must be ≤ ULN for the lab

- Measured or creatinine clearance must be ≥60ml/min

- Urinary protein should be 0- 1+ on dipstick urinalysis. If dipstick reading is
≥_2+ protein value must be < 500 mg in a 24-hour urine specimen.

11. Activated partial thromboplastin time (APTT) < 1.5 x ULN

12. Patients with synchronous bilateral breast cancer (diagnosed within one month) are
eligible if the higher tumour node metastasis (TNM) stage tumour meets the
eligibility criteria for this study and both are HER-2 negative.

13. Male or female patients age > 18 years of age are eligible.

14. Women must not be pregnant or breast-feeding due to the potential harmful effects of
bevacizumab on the developing fetus. (Note: All females of childbearing potential
must have a serum pregnancy test within 7 days prior to registration).

15. Women of childbearing potential and sexually active males must use an accepted and
effective method of contraception ( such as non hormonal intra uterine device (IUD),
condoms, sexual abstinence or vasectomized partner).

Exclusion Criteria:

1. Any active serious medical illness.

2. Patients must not have clinically significant cardiovascular or cerebrovascular
disease, including any history of

- Symptomatic heart disease or heart disease requiring ongoing treatment

- Cerebrovascular disease including transient ischemic attack (TIA), stroke or
subarachnoid haemorrhage

- Ischemic bowel

- Myocardial infarction

- Unstable angina

3. New York Heart Association (NYHA) grade II or greater congestive heart failure

4. Grade II or greater peripheral vascular disease active at study entry

5. Patients receiving anticoagulation therapy are excluded.

6. Uncontrolled hypertension defined as systolic blood pressure (BP) >145mmHg or
diastolic BP >85mmHg, with or without anti-hypertensive medication.(BP must be
assessed within 28 days prior to registration).

7. Uncontrolled or clinically significant arrhythmia.

8. Clinical evidence of inflammatory breast cancer or fixed axillary nodes at diagnosis.

9. Any major surgical procedure within 21 days of day 1 treatment. (NOTE: Non-operative
biopsy or placement of a vascular access device is not considered a major surgery).

10. Placement of a vascular access device within 24 hours of planned Day 1 of treatment.

11. Bleeding diathesis, hereditary or acquired bleeding disorder or coagulopathy.

12. A non-healing wound or fracture. Patients with an abdominal fistula, gastrointestinal
perforation, or intra-abdominal abscess within 6 months prior to registration are not

13. Axillary node involvement only demonstrated by immunohistochemistry are not eligible
unless they meet one of the other eligibility criteria below:

- ER negative tumour >2 cm invasive cancer

- ER positive tumour > 3 cm invasive cancer

14. Prior cancer except for basal cell skin cancer and cancer in situ of the cervix and

15. Hypersensitivity to Chinese hamster ovary cell products or other recombinant human

16. Patients must not have received prior cytotoxic chemotherapy for any cancer or
received hormonal therapy for this breast cancer.

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Percentage of patients experiencing heart failure

Outcome Description:

Patients will be followed up through 5 years (i.e. from the time of registration through to end of Year 5 / 1 year treatment and 4 years follow up)

Outcome Time Frame:

5 years

Safety Issue:


Principal Investigator

John Crown, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

ICORG- All Ireland Cooperative Oncology Research Group


Ireland: Irish Medicines Board

Study ID:




Start Date:

October 2008

Completion Date:

July 2016

Related Keywords:

  • Breast Cancer
  • estrogen receptor-negative breast cancer
  • estrogen receptor-positive breast cancer
  • HER2-negative breast cancer
  • stage IA breast cancer
  • stage IB breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • male breast cancer
  • Breast Neoplasms