Phase II clinical study of bevacizumab in combination with capecitabine as first-line treatment in elderly patients with metastatic breast cancer

• Conditions: Metastatic or locally recurrent HER2-negative breast cancer; MedDRA version: 12.0Level: LLTClassification code 10055113Term: Breast cancer metastatic; MedDRA version: 12.0Level: LLTClassification code 10006198Term: Breast cancer recurrent

• Registration Number: EUCTR2009-016062-82-HU
• Lead Sponsor: SOUTH EASTERN EUROPEAN RESEARCH ONCOLOGY GROUP

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-10-14
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

To be eligible for the study, each patient must fulfil all of the following inclusion criteria:
1.Signed informed consent obtained prior to initiation of any study specific procedures and treatment as confirmation of the patient’s awareness and willingness to comply with the study requirements;
2.Age = 70 years;
3.Pathologically confirmed and documented metastatic breast cancer or locally recurrent breast cancer not amenable to curative treatment. Complete radiology and tumor measurement workup must be completed within 4 weeks prior to first study treatment;
4.Measurable disease according to RECIST criteria;
5.HER2 negative disease;
6.No prior treatment for metastatic or locally recurrent disease;
7.Prior radiotherapy is allowed if delivered at least 2 weeks before enrolment in the study and for the relief of metastatic bone pain, and provided that no more than 30% of marrow-bearing bone was irradiated and that target lesions were not included in the radiotherapy field;
8.Not suitable for aggressive chemotherapy regimen in the opinion of the investigator;
9.Performance status ECOG 0 – 2.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
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.Any prior neoadjuvant or adjuvant treatment with anthracyclines completed less than 6 months prior to enrolment. The maximum cumulative dose received must not have exceeded 360 mg/m2 for doxorubicin or 720 mg/m2 for epirubicin. Prior anti-epidermal growth factor therapy is allowed;
2.Concurrent hormonal therapy; however previous hormonal therapy is allowed for adjuvant, locally recurrent, or metastatic breast cancer if completed within =1 months prior to enrollment;
3.History or clinical evidence of brain metastases. 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;
4.Other malignancy (including primary brain tumors) within the last 5 years, which could affect the diagnosis or assessment of breast cancer, except for adequately treated carcinoma in situ of the cervix, squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer;
5.Life expectancy < 12 weeks;
6.Any of the following abnormal values:
•Inadequate bone marrow function: hemoglobin (Hb) < 8.0 g/dL, absolute neutrophil count (ANC) < 1.5 x 109/L, or platelet count < 100 x 109/L;Inadequate liver function: AST/SGOT or ALT/SGPT > 2.5 x upper limit of normal (ULN) or > 5 x ULN in patients with liver metastases), serum alkaline phosphatase > 2.5 ULN or > 5 x ULN in patients with liver metastases, or > 10 x ULN in patients with bone metastases or total bilirubin > 2 x ULN; Moderate or severe renal impairment: creatinine clearance = 50 mL/min (calculated according to the Cockroft and Gault formula; see Appendix 1), or serum creatinine > 1.5 x ULN;
7.Chronic daily treatment with aspirin (> 325 mg/day) or clopidogrel (> 75 mg / day);
8.Chronic daily treatment with corticosteroids (dose of > 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids);
9.Requirement for concurrent use of the antiviral agents sorivudine or brivudine;
10.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;
11.Minor surgical procedures, within 24 hours prior to enrolment;
12. Current or recent (within the 30 days prior to starting study treatment) treatment with another investigational drug or participation in another investigational study.
13.Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (i.e. active) cardiovascular disease, including:
•Cerebrovascular accident/stroke (= 6 months prior to enrolment),
•Myocardial infarction (= 6 months prior to enrolment),
•Unstable angina,
•New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF)
•Serious cardiac arrhythmia requiring medication (with the exception of atrial fibrillation or paroxysmal supraventricular tachycardia);
14.History or evidence of inherited bleeding diathesis or coagulopathy with risk of bleeding;
•If the patient is receiving oral or parenteral anticoagulants, the dose must be stable for at least 2 weeks prior to the first study treatment and the INR, or appropriate monitoring test must be within therapeutic limits:
-Patients on heparin treatment should have an aPTT between 1.5-2.5 x ULN (or value before starting heparin treatment);
-Patients on low molecular weight heparins should receive 1.5–2.0 mg/kg of enoxaparin

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objective:<br>•Time to disease progression (TTP) <br><br><br>;Secondary Objective: Secondary objectives<br>•Objective response rate (ORR) in patients with measurable disease at baseline<br>•Clinical benefit (CR + PR + SD) in patients with measurable disease at baseline<br>•Progression-free survival (PFS)<br>•Overall survival (OS) <br>•Safety and tolerability ;Primary end point(s): Patients will be treated with capecitabine plus bevacizumab until disease progression, unacceptable toxicity, or patient request for discontinuation