Phase II Study With Abraxane, Bevacizumab and Carboplatin in Triple Negative Metastatic Breast Cancer (ABC)
Taxanes (such as paclitaxel) are highly active to treat breast cancer. Abraxane® (nanoparticle albumin-bound paclitaxel) compared to standard paclitaxel improves efficacy and tolerability. When combined with a taxane, platinum agents improve response in metastatic breast cancer, with carboplatin conferring less toxicity than cisplatin. Monoclonal antibodies including bevacizumab target vascular endothelial growth factor (VEGF) to reduce angiogenesis. We hypothesize that the previously-untested combination of weekly Abraxane® and carboplatin plus biweekly bevacizumab will lengthen time to progression without producing intolerable toxicity.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Abraxane®, Carboplatin and Bevacizumab in "Triple Negative" (Demonstrating No Expression for Estrogen, Progesterone, or Her2 Receptors) Metastatic Breast Cancer|
- Best Clinical Response Expressed as Percentage of Participants Treated With Combination Regimen of Weekly Abraxane® and Carboplatin Plus Biweekly Bevacizumab to Treat Women With Stage IV or Inoperable Stage III "Triple Negative" Metastatic Breast Cancer. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]Best clinical response is based on RECIST criteria, the proportion in each response category along with the exact binomial confidence intervals are estimated. Toxicity summaries are also provided.
- Median Proportion Progression-free as Estimated by Kaplan-Meier Methods [ Time Frame: 5 years ] [ Designated as safety issue: No ]PFS was defined as time from trial enrollment to disease progression or death, whichever occurred first.
- To Evaluate Sequential Plasma Samples for Presence of Selected Angiogenic Markers [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- to Determine if Apolipoprotein Alleles (Apo-E) Correlate With Treatment-related Neuropathy [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- to Determine if SPARC Expression in Breast Tumors Predicts Progression-free Survival (PFS) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2007|
|Study Completion Date:||March 2014|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Experimental: Abraxane, Carboplatin, Bevacizumab
Abraxane 100 mg/m2 IV over 30 min days 1,8,15.; Carboplatin AUC=2 IV over 15 min days 1,8,15., Bevacizumab 10 mg/kg IV days 1,15
100 mg/m2 IV over 30 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death..
Other Name: nanoparticle albumin-bound paclitaxelDrug: Bevacizumab
10 mg/kg IV days 1,15 Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria,intolerable toxicity, or death.
Other Name: AvastinDrug: Carboplatin
area under curve (AUC)=2 IV over 15 min days 1,8,15. Cycles Repeated Every 28 days until documented evidence of disease progression by RECIST criteria, intolerable toxicity, or death.
Anthracycline-based chemotherapy is widely used as adjuvant treatment for breast cancer. In addition to the challenge posed by anthracycline-induced cardiotoxicity, there are issues surrounding previous treatment with anthracyclines which limit its utility in the metastatic disease setting. Many patients with advanced disease will have had prior anthracycline-based adjuvant therapy, may have reached a maximum cumulative lifetime dose, or developed refractory disease, creating an obvious need for non-anthracycline treatment strategies.3 Platinum- and taxane-based chemotherapies as first-line therapy for metastatic breast cancer have demonstrated significant activity, producing single-agent response rates > 50%; in combination these rates increased to > 60% in both previously untreated and in patients who previously received anthracyclines.3 However, overall survival has remained relatively unchanged.4 As there is currently no standard of care for patients with metastatic breast cancer, various physical and psychological factors must be considered when evaluating chemotherapy treatment options, including the patient's tumor biology and growth rate, presence and extent of metastases, history of prior treatment and response, sensitivity and tolerance to therapy, and quality of life.2 Strategies to develop combination, higher dose, or sequential regimens using these active agents, while improving response rates and/or time to progression, may produce increased toxicity without increased survival.2 Because metastatic breast cancer remains essentially incurable using cytotoxic therapy alone, the study of targeted biologics offers new opportunities to enhance drug delivery via their ability to regulate specific receptors that are associated with clinically aggressive disease processes.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00479674
|United States, North Carolina|
|Presbyterian Health Care|
|Charlotte, North Carolina, United States, 28204|
|Northeast Oncology Associates|
|Concord, North Carolina, United States, 28205|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Forsyth Regional Cancer Center|
|Winston-Salem, North Carolina, United States, 27103-3019|
|Principal Investigator:||Kimberly Blackwell, MD||Duke University|