NCT00408408

Chemotherapy With or Without Bevacizumab in Treating Women With Stage I, Stage II, or Stage IIIA Breast Cancer That Can Be Removed By Surgery

A Randomized Phase III Trial of Neoadjuvant Therapy in Patients With Palpable and Operable Breast Cancer Evaluating the Effect on Pathologic Complete Response (pCR) of Adding Capecitabine or Gemcitabine to Docetaxel When Administered Before AC With or Without Bevacizumab and Correlative Science Studies Attempting to Identify Predictors of High Likelihood for pCR With Each of the Regimens

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,206 (actual)
• Sponsor: NSABP Foundation Inc · Network
• Sex: Female
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. 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. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy and bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known which chemotherapy regimen is more effective with or without bevacizumab in treating breast cancer. PURPOSE: This randomized phase III trial is studying six different chemotherapy regimens to compare how well they work with or without bevacizumab in treating women with stage I, stage II, or stage IIIA breast cancer that can be removed by surgery.

Detailed description

OBJECTIVES: Primary * Compare the efficacy of docetaxel followed by doxorubicin hydrocloride and cyclophosphamide (AC) vs docetaxel and capecitabine followed by AC vs docetaxel and gemcitabine hydrochloride followed by AC, with or without bevacizumab, in terms of an increase in the rate of pathologic complete response (pCR) in the breast, in women with palpable or operable breast cancer. Secondary * Compare docetaxel/capecitabine with AC vs docetaxel/gemcitabine hydrochloride with AC vs docetaxel with AC, with or without bevacizumab, in terms of the rate of pCR in the breast and all post-therapy lymph nodes evaluated histologically (pCR breast and nodes). * Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based regimens (docetaxel with AC, docetaxel and capecitabine with AC, and docetaxel and gemcitabine hydrochloride with AC) will increase the rate of pCR of the breast and nodes compared to the same docetaxel/anthracycline-based regimens without bevacizumab in these patients. * Determine whether the addition of capecitabine or gemcitabine hydrochloride to docetaxel, with or without bevacizumab, will increase the rate of clinical overall response (cOR) compared to docetaxel alone with or without bevacizumab in these patients. * Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based regimens will increase the rate of cOR compared to the same docetaxel/anthracycline-based regimens without bevacizumab in these patients. * Determine whether the addition of capecitabine or gemcitabine hydrochloride to docetaxel, with or without bevacizumab, will increase the rate of clinical complete response (cCR) compared to docetaxel alone with or without bevacizumab in these patients. * Determine whether the addition of bevacizumab to the docetaxel/anthracycline-based regimens (docetaxel with AC, docetaxel/capecitabine with AC, and docetaxel/gemcitabine hydrochloride with AC) will increase the rate of cCR compared to the same docetaxel/anthracycline-based regimens without bevacizumab in these patients. * Identify gene expression profiles that can predict pCR in patients treated with the different sequential docetaxel/anthracycline-based regimens with or without bevacizumab. * Identify gene expression profiles that can predict cOR in patients treated with docetaxel alone, docetaxel/capecitabine, or docetaxel/gemcitabine hydrochloride with or without bevacizumab. * Determine the accuracy of an in vitro chemoresponse assay (ChemoFx®) as a predictor of pCR in patients treated with the different sequential docetaxel/anthracycline-based regimens without bevacizumab. * Determine the accuracy of ChemoFx® as a predictor of cOR in patients treated with docetaxel alone, docetaxel/capecitabine, or docetaxel/gemcitabine hydrochloride without bevacizumab in these patients. * Determine the impact of preoperative bevacizumab and sequential chemotherapy regimens and postoperative bevacizumab therapy on cardiac function in these patients. * Determine the impact of bevacizumab on surgical complications in these patients. * Determine the toxicity of the preoperative regimens and the toxicity of postoperative bevacizumab in these patients. * Compare the docetaxel/anthracycline-based regimens with vs without bevacizumab, in terms of an increase in disease-free survival, of these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to tumor size (2-4 cm vs \> 4 cm), nodal status (negative vs positive), hormone receptor status (estrogen receptor \[ER\]-positive and/or progesterone-receptor \[PgR\]-positive vs ER- and PgR-negative), and age (\< 50 years vs ≥ 50 years). Patients are randomized to 1 of 6 treatment arms. Core needle biopsies are performed at baseline. Tumor tissue samples are also collected during definitive surgery. Samples are examined for gene expression and polymorphism by reverse transcriptase-polymerase chain reaction analysis and chemoresponse assay (ChemoFx®). After completion of study therapy, patients are followed periodically for 10 years. PROJECTED ACCRUAL: A total of 1,200 patients will be accrued for this study.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
BIOLOGICAL	bevacizumab	15 mg/kg IV
DRUG	capecitabine	825 mg/m2 orally
DRUG	cyclophosphamide	600 mg/m2 IV
DRUG	docetaxel	100 mg/m2 IV
DRUG	doxorubicin hydrochloride (Adriamycin)	60 mg/m2 IV
DRUG	gemcitabine hydrochloride	1000 mg/m2 IV

Timeline

• Start date: 2006-11-01
• Primary completion: 2011-03-01
• Completion: 2018-03-01
• First posted: 2006-12-07
• Last updated: 2017-09-18
• Results posted: 2017-09-18

Locations

442 sites across 3 countries: United States, Canada, Puerto Rico