A randomized, open-label, 2-arm, multicentre, phase III study to evaluate the efficacy and safety of bevacizumab in combination with trastuzumab / docetaxel compared with trastuzumab / docetaxel alone as first line treatment for patients with HER2 positive locally recurrent or metastatic breast cancer.

Conditions: First line treatment for patients with HER2 positive locally recurrent or metastatic breast cancer.
MedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer

Registration Number: EUCTR2006-001365-42-CZ

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 410

Inclusion Criteria

1. Patients age = 18 years
2. Able to comply with the protocol
3. ECOG PS of = 1
4. Life expectancy of = 12 weeks
5. Written informed consent [Informed Consent document to be approved by the
institution’s Independent Ethics Committee (IEC)] obtained prior to any study
specific screening activities.
6. Pre- or postmenopausal patients with histologically or cytologically confirmed
breast cancer (adenocarcinoma) with measurable or non-measurable, locally
recurrent or metastatic lesions, candidate for chemotherapy. Locally recurrent
disease must not be amenable to resection with curative intent ER/PgR and HER2
status must be documented.
7. Patients must have HER2 protein overexpression (3+) as determined by
immunohistochemistry (IHC); or amplification of HER2/c-erbB2 as determined by
fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) ,
of the primary tumor or a metastasis confirmed by the central laboratory prior to
randomization. Confirmation of HER2 positivity of the primary tumor by the central
laboratory is not required in this trial for the patients who previously participated
in Roche or Genentech sponsored trials of adjuvant Trastuzumab where HER2
status has been centrally confirmed (e.g. the HERA, BCIRG 006, NSABP B31, or
Intergroup/NCCTG/H2061s trials).
8. Patients who received trastuzumab in the adjuvant setting are eligible as long as
they have not relapsed within 6 months after the last dose of trastuzumab.
9. Patients who were treated with anthracyclines in adjuvant or neo-adjuvant
setting are only eligible if they received their last dose = 6 months prior to
randomization. The maximum cumulative dose must not exceed 360 mg/m2 for
doxorubicin and 720 mg/m2 for epirubicin
10. Patients who were treated with a taxane are only eligible if they received their
last adjuvant or neo-adjuvant chemotherapy = 12 months prior to
randomization. 11. Baseline Left Ventricular Ejection Fraction (LVEF) not below
50% measured by either echocardiography or MUGA
12. The use of full-dose oral or parenteral anticoagulants is permitted as long as the
patient has been on a stable level of anticoagulation for at least two weeks at
the time of randomization:
– Patients on heparin treatment should have a baseline aPTT between 1.5 - 2.5
times ULN or patients value before starting heparin treatment
– Patients on low molecular weight heparins (LMWH) should receive daily dose of
1.5 - 2 mg/kg (of enoxaparin) or appropriate doses of the correspondent
anticoagulant, according to package insert
– Patients on coumarin derivatives should have an INR between 2.0 and 3.0
assessed at baseline in two consecutive measurements 1-4 days apart
Patients not receiving anticoagulant medication must have an INR = 1.5 and aPTT = 1.5 times ULN within 7 days prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Previous chemotherapy for metastatic or locally recurrent breast cancer. Prior
hormonal therapy is allowed but must have been discontinued at least 2 weeks
prior randomization.
2. Previous radiotherapy for treatment of metastatic breast cancer is not allowed in
case:
- More than 30% of marrow-bearing bone have been irradiated
- The last fraction of radiotherapy has been administered within 3 weeks prior to
randomization
Prior adjuvant radiotherapy for breast cancer is allowed, provided it has stopped at least 6 months prior to randomization.
3. Other primary tumor (including primary brain tumors) within the last 5 years prior
to randomization, except for adequately treated carcinoma in situ of the cervix,
squamous carcinoma of the skin, or adequately controlled limited basal cell skin
cancer
4. Evidence of spinal cord compression or current evidence of CNS metastasis. CT or
MRI scan of the brain is mandatory (within 4 weeks prior to randomization) in
case of clinical suspicion of brain metastasis.
5. History or evidence upon physical/neurological examination of CNS disease
(unrelated to cancer) (unless adequately treated with standard medical therapy)
e.g. uncontrolled seizures
6. Major surgical procedure, open biopsy or significant traumatic injury within 28
days prior to study treatment start, or anticipation of the need for major surgery
during the course of the study treatment
7. Existing peripheral neuropathy > CTC Grade 2 at randomization.
8. Inadequate bone marrow function: ANC < 1.5 x 1'000'000'000/L, Platelet count <
100 x 1'000'000'000/L and Hb <9 g/dL
9. Inadequate liver function:
- serum (total) bilirubin > ULN
- AST and ALT > 2.5 x ULN
- AST or ALT > 1.5 x ULN concurrent with serum alkaline phosphatase levels
> 2.5 x ULN at baseline
10. Inadequate renal function:
i. Serum Creatinine > 2.0 mg/dL or 177 µmol/L
ii. Urine dipstick for proteinuria > 2+. Patients with = 2+ proteinuria on dipstick
urinalysis at baseline should undergo 24 hours urine collection and must
demonstrate = 1 g of protein/24 hr.
11. Chronic daily treatment with corticosteroids (dose of > 10 mg/day
methylprednisolone equivalent) (excluding inhaled steroids).
12. Chronic daily treatment with aspirin (> 325 mg / day) or clopidogrel (> 75 mg /
day).
13. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg)
or clinically significant (i.e. active) cardiovascular disease: CVA/stroke (= 6
months prior to randomization), myocardial infarction (= 6 months prior to
randomization), unstable angina, New York Heart Association (NYHA) Class 2 or
greater Congestive Heart Failure, or serious cardiac arrhythmia requiring
medication
14. History or evidence of inherited bleeding diathesis or coagulopathy with the risk
of bleeding
15. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months of randomization.
16. Active infection requiring i.v. antibiotics at randomization.
17. Serious non-healing wound, peptic ulcer, or bone fracture.
18. Evidence of any other disease, metabolic or psychological dysfunction, physical
examination finding, or clinical laboratory finding giving reasonable suspicion of a
disease or condition that contraindicates the use of an investigational drug, or
that may af