A phase II clinical trial is examining how well four neoadjuvant therapy (treatment before surgery) combinations of chemotherapy and bevacizumab (Avastin) work in treating women with triple-negative breast cancer that can be removed by surgery.
The study, which concludes in December 2012 when final data are collected, looks at the chemotherapy medicines paclitaxel with or without carboplatin and with or without the monoclonal antibody bevacizumab (Avastin) followed by the chemotherapy medicines doxorubicin and cyclophosphamide.
Background and Reason for the Study
Chemotherapy medicines like paciltaxel (Taxol), carboplatin (Paraplatin), doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) stop tumor cells from growing by either killing the cells or preventing them from dividing. Bevacizumab prevents tumor cells from growing by blocking blood flow to the tumor. This medicine also finds tumor cells and helps kill them or carry tumor-killing substances to them.
Neoadjuvant chemotherapy given together with bevacizumab may decrease tumor size in order to reduce the amount of healthy tissue that needs to be removed during surgery. Researchers are interested in how this approach works in women with stage II or III triple-negative breast cancer who require surgery.
Goals of the Study
The primary goal of this trial is to assess whether these treatment combinations raise the rate of pathologic complete response in triple-negative breast cancer that has not metastasized, or traveled to other parts of the body. Pathological complete response (pCR) means there is no evidence of invasive cancer after treatment.
History of Avastin
Bevacizumab was approved in the U.S. for certain types of colon, lung, brain and kidney cancers in 2004. The FDA granted accelerated approval for bevacizumab in 2008 for treatment of metastatic breast cancer, based on results indicating improvement in progression-free survival, the time between start of treatment and tumor progression.
Bevacizumab stirred controversy when the FDA withdrew approval in November 2011 for its use in treating HER2 negative metastatic breast cancer, stating that the medicine was not safe and effective. The agency ruled that while bevacizumab did impact progression-free survival, the risk of life-threatening side effects was too high for a medicine that did not prolong life. A recent study from the Cochrane Breast Cancer Group reached similar conclusions.
The ruling caused many women and advocates to protest in support of the treatment’s medical potential and because revoked FDA approval impacts whether insurance companies cover the cost of treatment.
Bevacizumab is available through clinical trials and can also be prescribed “off-label,” or for an unapproved use, which are typically not covered by insurance companies.
Bevacizumab is still approved for use in metastatic breast cancer in Europe.
Structure of Study
Participants are randomly divided according to clinical stage of disease into one of four treatment arms:
- Arm I – participants receive paclitaxel intravenously (by vein) over an hour once weekly for 12 weeks. They then receive dose-dense doxorubicin intravenously for five to 10 minutes, as well as cyclophosphamide for five to 30 minutes, once in weeks 13, 15, 17 and 19. (Pegfilgrastim (Neulasta), which helps stimulate white blood cells to fight off infection for those receiving chemotherapy, is also added to the dose-dense doxorubicin and cyclophosphamide part of the treatment.)
- Arm II – participants receive the same regimen as those in arm I, but they also receive bevacizumab intravenously for 30 to 90 minutes in weeks 1, 3, 5, 7, 9, 11, 13, 15 and 17.
- Arm III –this group receives the same treatment as those in arm I, with the addition of carboplatin intravenously for 30 minutes once in weeks 1, 4, 7 and 10.
- Arm IV – In addition to receiving the treatment in arm I, participants under this regimen receive bevacizumab as in arm II and carboplatin as in arm III.
All participants will undergo surgery between four and eight weeks after completing neoadjuvant treatment. The frequency and severity of side effects after surgery—including excessive bleeding, delayed wound healing and blood clots—will be examined. All participants will be followed for up to 10 years after completing the study treatment.
Who is Participating in This Study?
445 women and men ages 18 or older who have been diagnosed with stage II to III triple-negative breast cancer are participating in this study at 381 study locations nationwide.
None of the participants in this trial has inflammatory breast cancer. Participants will undergo surgery after completing neoadjuvant therapy.
Learn more about this study on the National Institutes of Health’s website.
Study Location and Activities
There are 381 locations for this study in the United States.
To learn about study locations by state, check out the NIH’s website
Contact lead investigator William M. Sikov, MD, at firstname.lastname@example.org or (401) 793-7151 to learn about the study.
You may also visit the National Cancer Institute’s website for additional information.