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Bevacizumab and Pegylated Liposomal Doxorubicin as First-Line Therapy for Locally Recurrent or Metastatic Breast Cancer. A Multicenter, Single-Arm Phase II Trial

Phase 2
18 Years
Not Enrolling
Breast Cancer

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Trial Information

Bevacizumab and Pegylated Liposomal Doxorubicin as First-Line Therapy for Locally Recurrent or Metastatic Breast Cancer. A Multicenter, Single-Arm Phase II Trial



- Determine the safety and tolerability of bevacizumab and doxorubicin hydrochloride
liposome in women with locally recurrent or metastatic breast cancer.


- Determine the efficacy of this regimen in these patients.

- Identify surrogate markers of angiogenesis, including vascular endothelial growth
factor (VEGF), VEGF receptor 1, and matrix metalloproteinase 9, in patients treated
with this regimen.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes and doxorubicin hydrochloride liposome IV
over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for up to 6 courses*.
Patients then receive bevacizumab alone IV over 30-90 minutes on days 1 and 15. Courses with
bevacizumab repeat every 4 weeks in the absence of disease progression or unacceptable

NOTE: *Patients may receive additional courses of doxorubicin hydrochloride liposome at the
discretion of the primary investigator.

Blood samples are collected at baseline, on day 1 of course 3 and then once every 3 months
during study treatment, and after completion of study treatment. Samples are analyzed by
enzyme-linked immunosorbent assay to determine the level of circulating angiogenesis-related
molecules, including serum vascular endothelial growth factor (VEGF), VEGF receptor 1, and
matrix metalloproteinase 9.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Inclusion Criteria


- Cytologically or histologically confirmed breast cancer

- Metastatic OR locally recurrent disease

- Unresectable disease

- Not amenable to radiotherapy

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- Measurable disease must be outside irradiated areas

- ErbB2-negative disease by immunohistochemistry (negative or 1+) or fluorescent in
situ hybridization (FISH)

- No known CNS metastases, even if previously treated

- Hormone receptor status not specified


- Female

- Menopausal status not specified

- WHO performance status 0-1

- LVEF ≥ 55%

- Hemoglobin ≥ 10.0 g/dL

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin < 2 times upper limit of normal (ULN)

- ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)

- Alkaline phosphatase (AP) ≤ 2.5 times ULN

- AP > 2.5 times ULN and ≤ 6 times ULN allowed if ALT ≤ 1.5 times ULN

- AP > 6 times ULN allowed if ALT normal

- Creatinine ≤ 1.5 times ULN

- Proteinuria < 2+ by dipstick OR protein ≤ 1 g/24hr-urine collection

- INR ≤ 1.5 OR Quick ≥ 70%

- aPTT ≤ 1.5 times ULN

- No peripheral neuropathy > grade 2

- No history or evidence of hereditary bleeding diathesis or coagulopathy with the risk
of bleeding

- No uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg
and/or diastolic BP > 100 mm Hg, measured repeatedly at > 2 visits despite adequate
treatment with ≥ 2 different antihypertensive drugs

- No clinically significant cardiovascular disease, including the following:

- Cerebrovascular accident or stroke within the past 6 months

- Myocardial infarction within the past 6 months

- Unstable angina

- New York Heart Association class II-IV congestive heart failure

- Serious cardiac arrhythmia (e.g., ventricular arrhythmia, high-grade
atrioventricular-block) not controlled by medication or requiring medication
which might interfere with regularity of the study treatment

- No serious nonhealing wound, active peptic ulcer, nonhealing bone fracture, or
bleeding skin metastases

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No active infection requiring IV antibiotics

- No known hypersensitivity to any of the study drugs or excipients

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human or humanized antibodies

- No evidence of any other disease that contraindicates the use of an investigational
drug, that may affect patient compliance with study routines, or places the patient
at high risk for treatment-related complications including, but not limited to, the

- Metabolic dysfunction

- Physical examination finding

- Psychological dysfunction

- Clinical laboratory finding giving reasonable suspicion of a disease or

- No known CNS disease unrelated to cancer (e.g., uncontrolled seizures), unless
adequately treated with standard medical therapy

- No high-risk factors for bleeding, including the following:

- Coagulation parameters outside range

- Need for concurrent anticoagulant therapy

- Insufficient time gap after surgical procedures

- No other malignancy within the past 5 years except for adequately treated basal cell
or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

- No significant traumatic injury within the past 28 days

- No known HIV positivity

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 12 months after
completion of study therapy


- No prior chemotherapy for metastatic or inoperable locally recurrent breast cancer

- No prior bevacizumab or other anti-vascular endothelial growth factor drug therapy

- No prior radiotherapy involving the heart (usual irradiation dose to breast or chest
wall allowed)

- More than 12 months since prior neoadjuvant or adjuvant chemotherapy

- No neoadjuvant or adjuvant doxorubicin hydrochloride with cumulative dose > 360 mg/m²
or epirubicin hydrochloride with cumulative dose > 720 mg/m²

- More than 6 months since prior adjuvant radiotherapy

- More than 28 days since prior major surgical procedure with high risk of bleeding

- More than 24 hours since prior minor surgical procedures

- More than 10 days since prior acetylsalicylic acid (> 325 mg/day) or clopidogrel
bisulfate (> 75 mg/day)

- More than 10 days since prior and no concurrent use of full-dose oral or parenteral
anticoagulants or thrombolytic agents for therapeutic purposes

- Prophylactic use of anticoagulants allowed (e.g., for maintenance of venous

- More than 30 days since prior investigational therapies or participation in other
investigational studies

- No concurrent hormonal therapy

- No other concurrent antineoplastic or antitumor therapy

- No other concurrent investigational drugs

- No concurrent radiotherapy

- No concurrent nonsteroidal anti-inflammatory drugs with activity on platelets and
gastric mucosa (e.g., dipyridamole, clopidogrel bisulfate, acetylsalicylic acid)

- No anticipated need for major surgery during the course of the study treatment

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

bevacizumab and doxorubicin hydrochloride liposome

Outcome Description:

Determine the safety and tolerability of bevacizumab and doxorubicin hydrochloride liposome.

Outcome Time Frame:

Until treatment ends

Safety Issue:


Principal Investigator

Christoph Rochlitz, MD

Investigator Role:

Study Chair

Investigator Affiliation:



Switzerland: Swissmedic

Study ID:

SAKK 24/06



Start Date:

December 2006

Completion Date:

March 2009

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IV breast cancer
  • Breast Neoplasms