Metronomic Therapy in Metastatic Breast Cancer.
- Conditions
- Breast Cancer
- Interventions
- Biological: Bevacizumab, Cyclophosphamide, CapecitabineBiological: bevacizumab, Paclitaxel
- Registration Number
- NCT01131195
- Lead Sponsor
- Swiss Group for Clinical Cancer Research
- Brief Summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as paclitaxel, cyclophosphamide, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether bevacizumab is more effective when given together with paclitaxel or cyclophosphamide and capecitabine in treating patients with breast cancer.
PURPOSE: This randomized phase III trial is studying the side effects of giving bevacizumab together with paclitaxel and to see how well it works compared with giving bevacizumab together with cyclophosphamide and capecitabine as first-line therapy in treating women with locally advanced, recurrent, or metastatic breast cancer.
- Detailed Description
OBJECTIVES:
* To determine if bevacizumab and paclitaxel versus bevacizumab, metronomic cyclophosphamide, and capecitabine as first-line therapy causes less medication-related adverse events in women with HER2-negative metastatic, locally advanced, or recurrent breast cancer.
* To compare quality of life (QOL) in patients treated with these regimens.
* To replicate previous findings of better QOL in patients with complete response or partial response versus stable disease for 6 months or greater.
* To determine the predictive value of baseline QOL for the duration of a meaningful change in QOL of patients treated with chemotherapy.
* To determine the associations between the QOL endpoints, selected health economics, and clinical endpoints.
OUTLINE: This is a multicenter study. Patients are stratified according to tumor response (measurable vs evaluable disease), WHO performance status (0 or 1 vs 2), and center. Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and paclitaxel IV on days 1, 8, and 15. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, oral cyclophosphamide once daily on days 1-28, and oral capecitabine 3 times a day on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Patients complete quality-of-life questionnaire (BL-QA) and health economics questionnaires (BL-HEA and EQ-5D) at baseline, during, and after completion of study therapy.
After completion of study treatment, patients are followed up at 1 month, every 3 months for 1 year, and then every 6 months for 1 year.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 139
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: bevacizumab, cyclophosphamide and capecitabine Bevacizumab, Cyclophosphamide, Capecitabine Bevacizumab (10 mg/kg) i.v. is given every two weeks. Cyclophosphamide (50 mg) and capecitabine (3x 500 mg) p.o. are given daily. All three medications are given until PD, unacceptable adverse event, or consent withdrawal. If an unacceptable adverse event to any of the drugs in this treatment arm occurs the remaining tolerated drug(s) is (are) given until PD, consent withdrawal, or unacceptable adverse event according to local investigators opinion Arm A: bevacizumab and paclitaxel bevacizumab, Paclitaxel Bevacizumab (10 mg/kg) i.v. is given every two weeks. Paclitaxel (90 mg/m2) i.v. is given on days 1, 8, and 15 of a 4 week cycle. Both medications are given until PD, unacceptable adverse event, or consent withdrawal. If an unacceptable adverse event to any of the drugs in this treatment arm occurs the remaining tolerated drug is given until PD, consent withdrawal, or unacceptable adverse event according to local investigators opinion.
- Primary Outcome Measures
Name Time Method Incidence of grade 3-5 adverse events Documentation of AE observed during trial treatment and in follow-up until resolution Patients who have experienced at least one of the adverse event grade ≥ 3 according to the NCI CTCAE criteria 4.0 are considered for the primary endpoint.
- Secondary Outcome Measures
Name Time Method Objective response (OR) the best response under trial treatment OR is the best response under trial treatment, defined as a complete response (CR) or partial response (PR) as assessed by RECIST v1.1.
Progression-free survival (PFS) from randomization until documented tumor progression PFS is calculated from randomization until documented tumor progression according to RECIST 1.1 or death of any cause, whichever occurs first.
Overall survival (OS) the time from randomization to death from any cause OS is defined as the time from randomization to death from any cause
Time to specific grade 3-5 adverse events Time from randomization until the first occurrence of the predefined grade 3-5 adverse events for the primary endpoint. Time from randomization until the first occurrence of the predefined grade 3-5 adverse events for the primary endpoint.
Disease control (DC) best response under trial treatment at 24 weeks after randomization DC is the best response under trial treatment, defined as CR + PR + stable disease.
Trial Locations
- Locations (23)
Hopital Cantonal Universitaire de Geneve
🇨🇭Geneva, Switzerland
Spitalzentrum Biel
🇨🇭Biel, Switzerland
Hirslanden Klinik Aarau
🇨🇭Aarau, Switzerland
Kantonsspital - St. Gallen
🇨🇭St. Gallen, Switzerland
Kantonsspital Baden
🇨🇭Baden, Switzerland
Universitaetsspital-Basel
🇨🇭Basel, Switzerland
RSV-GNW Spitalzentrum Oberwallis
🇨🇭Brig, Switzerland
Kantonsspital Graubuenden
🇨🇭Chur, Switzerland
Kantonsspital Frauenfeld
🇨🇭Frauenfeld, Switzerland
Kantonsspital Freiburg
🇨🇭Fribourg, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
Kantonsspital Luzern
🇨🇭Luzerne, Switzerland
Oncology Institute of Southern Switzerland - IOSI Ticino
🇨🇭Mendrisio, Switzerland
Kantonsspital Olten
🇨🇭Olten, Switzerland
Hopital Regional de Sion-Herens-Conthey
🇨🇭Sion, Switzerland
Regionalspital Thun
🇨🇭Thun, Switzerland
Spital Uster
🇨🇭Uster, Switzerland
Kantonsspital Winterthur
🇨🇭Winterthur, Switzerland
Onkozentrum - Klinik im Park
🇨🇭Zurich, Switzerland
Onkozentrum Hirslanden
🇨🇭Zurich, Switzerland
City Hospital Triemli
🇨🇭Zurich, Switzerland
UniversitaetsSpital Zuerich
🇨🇭Zurich, Switzerland
Kantonspital Aarau
🇨🇭Aarau, Switzerland