Metronomic Therapy in Metastatic Breast Cancer.
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.
|Breast Cancer||Biological: bevacizumab, Paclitaxel Biological: Bevacizumab, Cyclophosphamide, Capecitabine||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Safety and Tolerability of Bevacizumab Plus Paclitaxel vs. Bevacizumab Plus Metronomic Cyclophosphamide and Capecitabine as First-Line Therapy in Patients With HER2-Negative Metastatic or Locally Recurrent Breast Cancer - A Multicenter, Randomized Phase III Trial.|
- Incidence of grade 3-5 adverse events [ Time Frame: 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.
- Objective response (OR) [ Time Frame: 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.
- Disease control (DC) [ Time Frame: best response under trial treatment at 24 weeks after randomization ]DC is the best response under trial treatment, defined as CR + PR + stable disease.
- Progression-free survival (PFS) [ Time Frame: 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) [ Time Frame: 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 Frame: 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.
|Actual Study Start Date:||July 19, 2010|
|Estimated Study Completion Date:||June 30, 2019|
|Primary Completion Date:||December 14, 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Arm A: bevacizumab and 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.
Biological: 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.
Other Name: Avastin
Active Comparator: Arm B: bevacizumab, cyclophosphamide and 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
Biological: 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
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01131195
|Hirslanden Klinik Aarau|
|Aarau, Switzerland, CH-5001|
|Aarau, Switzerland, CH-5001|
|Baden, Switzerland, CH-5404|
|Basel, Switzerland, CH-4031|
|Biel, Switzerland, CH-2501|
|RSV-GNW Spitalzentrum Oberwallis|
|Brig, Switzerland, 3900|
|Chur, Switzerland, CH-7000|
|Frauenfeld, Switzerland, 8501|
|Fribourg, Switzerland, 1708|
|Hopital Cantonal Universitaire de Geneve|
|Geneva, Switzerland, CH-1211|
|Centre Hospitalier Universitaire Vaudois|
|Lausanne, Switzerland, CH-1011|
|Luzerne, Switzerland, CH-6000|
|Oncology Institute of Southern Switzerland - IOSI Ticino|
|Mendrisio, Switzerland, CH-6850|
|Olten, Switzerland, CH-4600|
|Hopital Regional de Sion-Herens-Conthey|
|Sion, Switzerland, CH -1951|
|Kantonsspital - St. Gallen|
|St. Gallen, Switzerland, CH-9007|
|Thun, Switzerland, 3600|
|Uster, Switzerland, 8610|
|Winterthur, Switzerland, 8401|
|Onkozentrum - Klinik im Park|
|Zurich, Switzerland, 8002|
|Zurich, Switzerland, CH-8008|
|City Hospital Triemli|
|Zurich, Switzerland, CH-8063|
|Zurich, Switzerland, CH-8091|
|Study Chair:||Christoph Rochlitz, MD||Universitaetsspital-Basel|
|Study Chair:||Ralph Winterhalder, MD||Luzerner Kantonsspital|