A single arm, open-label, multicentre, phase II study to evaluate the efficacy and safety of bevacizumab and trastuzumab combination and sequential capecitabine in patients with HER2-positive locally recurrent or metastatic breast cancer after early relapse to adjuvant trastuzumab-containing therapy

• Conditions: Male or female patients with locally recurrent or metastatic HER2-positive breast cancer who have relapsed early after adjuvant treatment that included trastuzumab and who have not received prior chemotherapy for their locally recurrent or metastatic disease; MedDRA version: 9.1Level: HLGTClassification code 10006291Term: Breast neoplasms malignant and unspecified (incl nipple)

• Registration Number: EUCTR2008-007495-20-AT
• Lead Sponsor: Roche Austria GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02-24
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Male or female, age = 18 years.
2.Pathologically confirmed breast adenocarcinoma with measurable (per RECIST, see Appendix 2) or non-measurable, locally recurrent or metastatic lesions.
3.Documented HER2 protein overexpression as determined by immunohistochemistry (IHC) 3+ or by demonstrated HER2/c-erbB2 gene amplification according to fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) of the primary tumor by a local or central laboratory.
4.Candidates for chemotherapy. Locally advanced disease must not be amenable to resection with curative intent.
5.Most recent prior systemic treatment for breast cancer was adjuvant therapy that included trastuzumab. Disease progression must have occurred during adjuvant treatment or up to 12 months from completion of adjuvant treatment. Radiotherapy may have been received after adjuvant therapy, however patients should have recovered from any acute reversible toxicity.
6.LVEF = 55% measured by either echocardiography or multiple gated nuclear angiography (MUGA) within 6 weeks of study treatment initiation.
7.ECOG Performance Status = 1
8.Able and willing to comply with the protocol.
9.Written informed consent, obtained prior to beginning any study-specific procedures.
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 treatment for locally advanced or metastatic breast cancer other than radiotherapy. Patients must have fully recovered from side effects of any prior radiotherapy.
2.Prior treatment with bevacizumab or capecitabine.
3.Prior neoadjuvant or adjuvant treatment with anthracyclines if the maximum cumulative dose was greater than 360 mg/m2 of doxorubicin or 720 mg/m2 of epirubicin.
4.Chronic daily treatment with corticosteroids (dose of > 10 mg/day methylprednisolone equivalent) excluding inhaled steroids.
5.Chronic daily treatment with aspirin (>325 mg/day) or clopidogrel (> 75 mg / day).
6.Requirement for concurrent use of the antiviral agent sorivudine, or chemically related analogues, such as brivudine.
7.Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to enrolment, or anticipation of the need for major surgery during the course of the study treatment.
8.Current or recent (within the 30 days prior to starting study treatment) treatment with another investigational drug or participation in another investigational study.
13.Other primary malignancy which could affect compliance with the protocol or interpretation of results. Patients treated with curative intent and disease-free for at least 5 years and patients treated curatively for carcinoma in situ of the cervix or non-melanomatous skin cancer may be included.
14.Evidence of CNS metastasis. If there is any clinical suspicion of brain metastasis, a computerized tomography (CT) scan or magnetic resonance imaging (MRI) of the brain must be conducted within 4 weeks prior to enrolment.
15.Evidence of spinal cord compression caused by metastases.
16.Serious concurrent disease which could affect compliance with the protocol or interpretation of results, including, but not limited to:
17.Active infection requiring IV antibiotics.
18.Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg).
19.Clinically significant (i.e. active) cardiovascular disease as indicated by: cerebrovascular accident or stroke = 6 months prior to study entry; myocardial infarction = 6 months prior to study entry; unstable angina; New York Heart Association (NYHA) (see Appendix 4) Grade II or greater CHF; serious cardiac arrhythmia requiring medication; clinically significant valvular heart disease.
20.Dyspnea at rest necessitating supportive oxygen therapy or with significant pleural effusions.
21.Poorly controlled diabetes mellitus.
22.Cardiac toxicity during previous trastuzumab treatment that necessitated discontinuation of trastuzumab.
23.History or evidence upon physical/neurological examination of CNS disease unrelated to cancer (e.g. uncontrolled seizures) unless adequately treated with standard medical therapy.
24.History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
25. History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months of study entry.
26.Serious non-healing wound, peptic ulcer, or bone fracture.
35.Pregnant or lactating females. For women of childbearing potential, serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified