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

• ClinicalTrials.gov Identifier: NCT00408408
• Recruitment Status: Unknown
• First Posted: December 7, 2006
• Results First Posted: September 18, 2017
• Last Update Posted: September 18, 2017
• Sponsor: NSABP Foundation Inc
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): NSABP Foundation Inc

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer
• Interventions: Biological: bevacizumab; Drug: capecitabine; Drug: cyclophosphamide; Drug: docetaxel; Drug: doxorubicin hydrochloride (Adriamycin); Drug: gemcitabine hydrochloride
• Enrollment: 1206

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Period Title: Overall Study
Started	201	199	204	201	197	204
Completed	199	196	204	194	192	201
Not Completed	2	3	0	7	5	3
Reason Not Completed
No follow up data	2	3	0	7	5	3

Baseline Characteristics

Arm/Group Title		Docetaxel Then AC	Docetaxel + Bev Then AC + Bev	Docetaxel + Capecitabine Then AC	Docetaxel + Cape + Bev Then AC + Bev	Docetaxel + Gem Then AC	Docetaxel + Gem + Bev Then AC + Bev	Total
Arm/Group Description		Docetaxel then AC	Docetaxel + Bev then AC + Bev	Docetaxel + Capecitabine then AC	Docetaxel + Cape + Bev then AC + Bev	Docetaxel + Gem then AC	Docetaxel + Gem + Bev then AC + Bev	Total of all reporting groups
Overall Number of Baseline Participants		201	199	204	201	197	204	1206
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	201 participants	199 participants	204 participants	201 participants	197 participants	204 participants	1206 participants
		48 (9.1)	49 (9.6)	49 (9.8)	49 (10.4)	48 (9.9)	48 (9.8)	48 (9.7)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	201 participants	199 participants	204 participants	201 participants	197 participants	204 participants	1206 participants
	Female	201 100.0%	199 100.0%	204 100.0%	201 100.0%	197 100.0%	204 100.0%	1206 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response (pCR) of the Primary Tumor in the Breast
Description	Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen.
Time Frame	Time of surgery, on average 6 or 13 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description:	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Overall Number of Participants Analyzed	199	196	204	194	192	201
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	33.7; (27.1 to 40.2)	31.6; (25.1 to 38.1)	23.5; (17.7 to 29.4)	36.1; (29.3 to 42.8)	27.6; (21.3 to 33.9)	35.8; (29.2 to 42.4)

2. Secondary Outcome

Title	pCR in the Breast and Nodes
Description	Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes.
Time Frame	Time of surgery, on average 6 or 13 months

Outcome Measure Data

Analysis Population Description

Arm 1A there is no follow up data for 3 patients; Arm 1B no follow up date for 6 patients; Arm 2A no follow up data for 1 patient; Arm 2B no follow up data for 11 patients; Arm 3A no follow up data for 9 patients; and Arm 3B no follow up data for 6 patients

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description:	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Overall Number of Participants Analyzed	198	193	203	190	188	198
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	27.3; (21.3 to 33.6)	24.4; (18.6 to 30.6)	18.7; (13.7 to 24.4)	27.4; (21.2 to 33.8)	22.9; (17.2 to 29.1)	30.3; (24.1 to 36.8)

3. Secondary Outcome

Title	Clinical Overall Response (cOR) Following Docetaxel Alone, Docetaxel/Capecitabine, and Docetaxel/Gemcitabine Hydrochloride, With or Without Bevacizumab, as Assessed by Physical Exam at the Completion of the Docetaxel-based Portion of Chemotherapy
Description	Percentages of patients assessed as Clinical Complete Response or Clinical Partial Response according to RECIST.
Time Frame	Assessed at cycle 5 of chemotherapy, on average at 15 weeks

Outcome Measure Data

Analysis Population Description

For Arm 1A there is no follow up data for 1 patient; Arm 1B no follow up data for 5 patients; Arm 2A no follow up data for 6 patients; Arm 2B no follow up data for 7 patients; Arm 3A no follow up data for 7 patients; Arm 3B no follow up data for 4 patients

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description:	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Overall Number of Participants Analyzed	200	194	198	194	190	200
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	77; (70.5 to 82.2)	87.6; (82.1 to 91.5)	73.7; (67 to 79.3)	84; (78.1 to 88.5)	82.6; (76.5 to 87.3)	88; (82.6 to 91.8)

4. Secondary Outcome

Title	Clinical Overall Response: cOR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens
Description	The percentage of patients assessed by physical exam as Clinical Complete Response or Clinical Partial Response according to RECIST.
Time Frame	Three to four weeks after the last chemotherapy dose on average 6 or 13 months

Outcome Measure Data

Analysis Population Description

For Arm 1A there is no follow up data for 2 patients; Arm 1B no follow up data for 4 patients; Arm 2A no follow up data for 5 patients; Arm 2B no follow up data for 8 patients; Arm 3A no follow up data for 5 patients; Arm 3B no follow up data for 4 patients

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description:	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Overall Number of Participants Analyzed	199	195	199	193	192	200
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	79.9; (73.6 to 84.8)	87.7; (82.2 to 91.6)	75.4; (68.8 to 80.8)	90.7; (85.6 to 94)	83.3; (77.3 to 87.9)	80.5; (74.3 to 85.4)

5. Secondary Outcome

Title	Clinical Complete Response (cCR) Following Docetaxel Alone, Docetaxel/Capecitabine, and Docetaxel/Gemcitabine Hydrochloride, With or Without Bevacizumab, as Assessed by Physical Exam at Completion of Therapy
Description	Percentages of patients assessed as Clinical Complete Response or Clinical Partial Response according to RECIST.
Time Frame	Assessed at cycle 5 of chemotherapy, on average at 15 weeks

Outcome Measure Data

Analysis Population Description

For Arm 1A there is no follow up data for 2 patients; Arm 1B no follow up data for 4 patients; Arm 2A no follow up data for 5 patients; Arm 2B no follow up data for 8 patients; Arm 3A no follow up data for 5 patients; Arm 3B no follow up data for 4 patients

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description:	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Overall Number of Participants Analyzed	199	195	199	193	192	200
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	30; (23.8 to 36.4)	43.3; (36.3 to 50.1)	29.8; (23.6 to 36.2)	34.5; (27.9 to 41.2)	37.9; (31 to 44.7)	42; (35.1 to 48.7)

6. Secondary Outcome

Title	Clinical Complete Resonse: cCR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens
Description	The percentage of patients assessed by physical exam as Clinical Complete Response according to RECIST.
Time Frame	Three to four weeks after the last chemotherapy dose, on average at 6 or 13 months

Outcome Measure Data

Analysis Population Description

For Arm 1A there is no follow up data for 2 patients; Arm 1B no follow up data for 4 patients; Arm 2A no follow up data for 5 patients; Arm 2B no follow up data for 8 patients; Arm 3A no follow up data for 5 patients; Arm 3B no follow up data for 4 patients

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description:	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Overall Number of Participants Analyzed	199	195	199	193	192	200
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	52.3; (45.1 to 58.9)	64.6; (57.5 to 70.9)	51.3; (44.1 to 57.9)	59.1; (51.8 to 65.6)	52.6; (45.3 to 59.4)	60; (52.9 to 66.4)

7. Secondary Outcome

Title	Percentage of Cardiac Events
Description	[Not Specified]
Time Frame	After each cycle, 3-5 weeks postoperative, 9 and 12 months from study entry, every 6 month years 2-5, and annually years 6-10, for postoperative bevacizumab patients, every 6 weeks during postoperative therapy and at 18 months following study entry.

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	Surgical Complication
Description	Number of patients with Grade 4 or above surgery-related toxicities
Time Frame	24 months after study entry

Outcome Measure Data

Analysis Population Description

For Arm 1A there is no follow up data for 8 patients; Arm 1B no follow up data for 8 patients; Arm 2A no follow up data for 6 patients; Arm 2B no follow up data for 12 patients; Arm 3A no follow up data for 11 patients; Arm 3B no follow up data for 7 patients

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description:	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Overall Number of Participants Analyzed	193	191	198	189	186	197
Measure Type: Number; Unit of Measure: participants
	1	1	0	1	0	1

9. Secondary Outcome

Title	Toxicities Including Events Other Than Congestive Heart Failure, of Chemotherapy Alone, Bevacizumab With Chemotherapy, and Bevacizumab Alone
Description	The number of patients who experienced Grade 1 or above Adverse Events. Referring to the Adverse Events tables for specifics.
Time Frame	24 months after study entry

Outcome Measure Data

Analysis Population Description

For Arm 1A there is no followup data for 2 patients; for Arm 2A there is no followup data for 1 patient; for Arm 3A there is no followup data for 3 patients; for Arm 1B there is no followup data for 3 patients; for Arm 2B there is no followup data for 5 patients; and for Arm 3B there is no followup data for 2 patients.

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description:	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Overall Number of Participants Analyzed	199	196	203	196	194	202
Measure Type: Number; Unit of Measure: participants
	180	157	172	185	158	185

10. Secondary Outcome

Title	Disease-free Survival (DFS)
Description	Percentage of patients free from local recurrence following mastectomy, local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer after 5 years.
Time Frame	Measured through 5 years after study enrollment

Outcome Measure Data

Analysis Population Description

For Arm 1A there is no follow up data for 2 patients; Arm 1B no follow up data for 4 patients; Arm 2B no follow up data for 6 patients; Arm 3A no follow up data for 7 patients; Arm 3B no follow up data for 3 patients

Arm/Group Title	Arm 1A: Docetaxel Then AC	Arm 1B Docetaxel + Bev Then AC + Bev	Arm 2A: Docetaxel + Capecitabine Then AC	Arm 2B: Docetaxel + Cape + Bev Then AC + Bev	Arm 3A: Docetaxel + Gem Then AC	Arm 3B: Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description:	Patients receive docetaxel IV on day 1 every 3 weeks for up to 4 cycles. Patients then receive AC IV every 3 weeks for up to 4 cycles. Patients then undergo surgery (lumpectomy or mastectomy). cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab (bev) IV on day 1 and docetaxel every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab IV every 3 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and oral capecitabine (cape) twice daily on days 1-14 every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive bevacizumab as in Arm 1B and docetaxel and capecitabine as in Arm III. Treatment repeats every 3 weeks for up to 4 cycles. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1B. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV capecitabine: 825 mg/m2 orally cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV	Patients receive docetaxel as in Arm 1A and gemcitabine hydrochloride IV on days 1 and 8 of each cycle every 3 weeks for up to 4 cycles. Patients then receive AC as in Arm 1A. Patients then undergo surgery as in Arm 1A. cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV	Patients receive docetaxel as in Arm 1A, gemcitabine hydrochloride as in Arm 3A, and bevacizumab as in Arm 1B. Patients then receive AC every 3 weeks for up to 4 cycles and 2 additional cycles of bevacizumab concurrent with the first 2 cycles of AC. Patients then undergo surgery as in Arm 1A. At least 4-6 weeks after surgery, patients receive adjuvant bevacizumab as in Arm 1B. bevacizumab: 15 mg/kg IV cyclophosphamide: 600 mg/m2 IV docetaxel: 100 mg/m2 IV doxorubicin hydrochloride (Adriamycin): 60 mg/m2 IV gemcitabine hydrochloride: 1000 mg/m2 IV
Overall Number of Participants Analyzed	199	195	204	195	190	201
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	73.4; (66.2 to 79.3)	72.2; (65.1 to 78.1)	68.5; (61 to 74.9)	77.1; (69.7 to 82.9)	72.9; (65.3 to 79.1)	74.8; (66.1 to 81.5)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	Participants at Risk includes any patient who submitted an AE form.
Arm/Group Title	Docetaxel Then AC	Docetaxel + Bev Then AC + Bev	Docetaxel + Capecitabine Then AC	Docetaxel + Cape + Bev Then AC + Bev	Docetaxel + Gem Then AC	Docetaxel + Gem + Bev Then AC + Bev
Arm/Group Description	Docetaxel then AC	Docetaxel + Bev then AC + Bev	Docetaxel + Capecitabine then AC	Docetaxel + Cape + Bev then AC + Bev	Docetaxel + Gem then AC	Docetaxel + Gem + Bev then AC + Bev
All-Cause Mortality
	Docetaxel Then AC	Docetaxel + Bev Then AC + Bev	Docetaxel + Capecitabine Then AC	Docetaxel + Cape + Bev Then AC + Bev	Docetaxel + Gem Then AC	Docetaxel + Gem + Bev Then AC + Bev
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events
	Docetaxel Then AC	Docetaxel + Bev Then AC + Bev	Docetaxel + Capecitabine Then AC	Docetaxel + Cape + Bev Then AC + Bev	Docetaxel + Gem Then AC	Docetaxel + Gem + Bev Then AC + Bev
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/199 (2.01%)	15/196 (7.65%)	8/203 (3.94%)	30/196 (15.31%)	2/194 (1.03%)	15/202 (7.43%)
Blood and lymphatic system disorders
Anemia † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Blood and lymphatic system disorders - Other, specify † 1	0/199 (0.00%)	1/196 (0.51%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Cardiac disorders
Cardiac arrest † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	1/202 (0.50%)
Heart failure † 1	0/199 (0.00%)	1/196 (0.51%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	1/202 (0.50%)
Myocardial infarction † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	1/202 (0.50%)
Pericardial effusion † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Left ventricular systolic dysfunction † 1	0/199 (0.00%)	1/196 (0.51%)	1/203 (0.49%)	5/196 (2.55%)	0/194 (0.00%)	2/202 (0.99%)
Gastrointestinal disorders
Abdominal pain † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Colonic hemorrhage † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Colonic perforation † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	1/202 (0.50%)
Small intestinal perforation † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	1/202 (0.50%)
Lower gastrointestinal hemorrhage † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Anal hemorrhage † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	1/202 (0.50%)
Upper gastrointestinal hemorrhage † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
General disorders
Sudden death NOS † 1	0/199 (0.00%)	0/196 (0.00%)	1/203 (0.49%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Immune system disorders
Anaphylaxis † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Infections and infestations
Endocarditis infective † 1	0/199 (0.00%)	1/196 (0.51%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Infections and infestations - Other, specify † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	1/194 (0.52%)	0/202 (0.00%)
Sepsis † 1	0/199 (0.00%)	1/196 (0.51%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Abdominal infection † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Lung infection † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	1/202 (0.50%)
Injury, poisoning and procedural complications
Wound dehiscence † 1	0/199 (0.00%)	2/196 (1.02%)	0/203 (0.00%)	3/196 (1.53%)	0/194 (0.00%)	2/202 (0.99%)
Investigations
Cardiac troponin I increased † 1	0/199 (0.00%)	0/196 (0.00%)	1/203 (0.49%)	1/196 (0.51%)	0/194 (0.00%)	1/202 (0.50%)
Creatinine increased † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	1/194 (0.52%)	0/202 (0.00%)
Investigations - Other, specify † 1	0/199 (0.00%)	0/196 (0.00%)	1/203 (0.49%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Metabolism and nutrition disorders
Dehydration † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	2/202 (0.99%)
Hyperkalemia † 1	1/199 (0.50%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Hypokalemia † 1	2/199 (1.01%)	0/196 (0.00%)	0/203 (0.00%)	2/196 (1.02%)	1/194 (0.52%)	1/202 (0.50%)
Hyponatremia † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	1/202 (0.50%)
Hypophosphatemia † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Musculoskeletal and connective tissue disorders
Myositis † 1	0/199 (0.00%)	0/196 (0.00%)	1/203 (0.49%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukemia secondary to oncology chemotherapy † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Treatment related secondary malignancy † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Nervous system disorders
Headache † 1	0/199 (0.00%)	1/196 (0.51%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Nervous system disorders - Other, specify † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	2/202 (0.99%)
Psychiatric disorders
Anxiety † 1	0/199 (0.00%)	0/196 (0.00%)	1/203 (0.49%)	0/196 (0.00%)	0/194 (0.00%)	1/202 (0.50%)
Depression † 1	0/199 (0.00%)	1/196 (0.51%)	1/203 (0.49%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Renal and urinary disorders
Proteinuria † 1	0/199 (0.00%)	4/196 (2.04%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	1/202 (0.50%)
Reproductive system and breast disorders
Uterine hemorrhage † 1	0/199 (0.00%)	1/196 (0.51%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnea † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	2/196 (1.02%)	0/194 (0.00%)	1/202 (0.50%)
Epistaxis † 1	0/199 (0.00%)	1/196 (0.51%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	1/202 (0.50%)
Pneumothorax † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Pleural hemorrhage † 1	0/199 (0.00%)	0/196 (0.00%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome † 1	0/199 (0.00%)	1/196 (0.51%)	1/203 (0.49%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Vascular disorders
Hypertension † 1	0/199 (0.00%)	1/196 (0.51%)	0/203 (0.00%)	1/196 (0.51%)	0/194 (0.00%)	0/202 (0.00%)
Thromboembolic event † 1	1/199 (0.50%)	1/196 (0.51%)	2/203 (0.99%)	4/196 (2.04%)	0/194 (0.00%)	1/202 (0.50%)
Vascular disorders - Other, specify † 1	0/199 (0.00%)	0/196 (0.00%)	1/203 (0.49%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
Visceral arterial ischemia † 1	1/199 (0.50%)	0/196 (0.00%)	0/203 (0.00%)	0/196 (0.00%)	0/194 (0.00%)	0/202 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE v4.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Docetaxel Then AC	Docetaxel + Bev Then AC + Bev	Docetaxel + Capecitabine Then AC	Docetaxel + Cape + Bev Then AC + Bev	Docetaxel + Gem Then AC	Docetaxel + Gem + Bev Then AC + Bev
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	118/199 (59.30%)	150/196 (76.53%)	168/203 (82.76%)	182/196 (92.86%)	150/194 (77.32%)	178/202 (88.12%)
Blood and lymphatic system disorders
Febrile neutropenia † 1	5/199 (2.51%)	18/196 (9.18%)	14/203 (6.90%)	23/196 (11.73%)	16/194 (8.25%)	19/202 (9.41%)
Gastrointestinal disorders
Diarrhea † 1	26/199 (13.07%)	27/196 (13.78%)	52/203 (25.62%)	43/196 (21.94%)	41/194 (21.13%)	43/202 (21.29%)
Mucositis oral † 1	22/199 (11.06%)	54/196 (27.55%)	56/203 (27.59%)	83/196 (42.35%)	38/194 (19.59%)	58/202 (28.71%)
Nausea † 1	4/199 (2.01%)	9/196 (4.59%)	8/203 (3.94%)	10/196 (5.10%)	13/194 (6.70%)	9/202 (4.46%)
Vomiting † 1	6/199 (3.02%)	4/196 (2.04%)	9/203 (4.43%)	7/196 (3.57%)	16/194 (8.25%)	8/202 (3.96%)
General disorders
Fatigue † 1	18/199 (9.05%)	18/196 (9.18%)	21/203 (10.34%)	21/196 (10.71%)	14/194 (7.22%)	22/202 (10.89%)
Infections and infestations
Infections and infestations - Other, specify † 1	4/199 (2.01%)	11/196 (5.61%)	8/203 (3.94%)	16/196 (8.16%)	7/194 (3.61%)	20/202 (9.90%)
Investigations
Alanine aminotransferase increased (ALT/SGPT) † 1	2/199 (1.01%)	9/196 (4.59%)	10/203 (4.93%)	7/196 (3.57%)	26/194 (13.40%)	35/202 (17.33%)
Aspartate aminotransferase increased (AST/SGOT) † 1	3/199 (1.51%)	7/196 (3.57%)	5/203 (2.46%)	8/196 (4.08%)	18/194 (9.28%)	27/202 (13.37%)
Neutrophil count decreased † 1	28/199 (14.07%)	30/196 (15.31%)	42/203 (20.69%)	37/196 (18.88%)	64/194 (32.99%)	70/202 (34.65%)
White blood cell decreased † 1	6/199 (3.02%)	14/196 (7.14%)	14/203 (6.90%)	7/196 (3.57%)	22/194 (11.34%)	16/202 (7.92%)
Metabolism and nutrition disorders
Hyperglycemia † 1	11/199 (5.53%)	3/196 (1.53%)	6/203 (2.96%)	3/196 (1.53%)	5/194 (2.58%)	5/202 (2.48%)
Musculoskeletal and connective tissue disorders
Bone pain † 1	10/199 (5.03%)	16/196 (8.16%)	1/203 (0.49%)	7/196 (3.57%)	6/194 (3.09%)	4/202 (1.98%)
Myalgia † 1	10/199 (5.03%)	9/196 (4.59%)	3/203 (1.48%)	11/196 (5.61%)	4/194 (2.06%)	3/202 (1.49%)
Nervous system disorders
Headache † 1	1/199 (0.50%)	7/196 (3.57%)	2/203 (0.99%)	7/196 (3.57%)	2/194 (1.03%)	11/202 (5.45%)
Peripheral motor neuropathy † 1	8/199 (4.02%)	4/196 (2.04%)	3/203 (1.48%)	13/196 (6.63%)	4/194 (2.06%)	4/202 (1.98%)
Peripheral sensory neuropathy † 1	33/199 (16.58%)	35/196 (17.86%)	29/203 (14.29%)	40/196 (20.41%)	19/194 (9.79%)	21/202 (10.40%)
Renal and urinary disorders
Proteinuria † 1	0/199 (0.00%)	12/196 (6.12%)	0/203 (0.00%)	5/196 (2.55%)	0/194 (0.00%)	10/202 (4.95%)
Respiratory, thoracic and mediastinal disorders
Dyspnea † 1	11/199 (5.53%)	10/196 (5.10%)	5/203 (2.46%)	9/196 (4.59%)	11/194 (5.67%)	14/202 (6.93%)
Skin and subcutaneous tissue disorders
Rash maculo-papular † 1	22/199 (11.06%)	22/196 (11.22%)	11/203 (5.42%)	29/196 (14.80%)	33/194 (17.01%)	38/202 (18.81%)
Palmar-plantar erythrodysesthesia syndrome † 1	13/199 (6.53%)	32/196 (16.33%)	92/203 (45.32%)	110/196 (56.12%)	5/194 (2.58%)	14/202 (6.93%)
Vascular disorders
Hypertension † 1	4/199 (2.01%)	49/196 (25.00%)	3/203 (1.48%)	43/196 (21.94%)	2/194 (1.03%)	49/202 (24.26%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE v4.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Director, Department of Regulatory Affairs
• Organization: NSABP Foundation, Inc
• Phone: 412-339-5300
• EMail: regulatory@nsabp.org

Publications of Results:

Bear HD, Tang G, Rastogi P, Geyer CE Jr, Robidoux A, Atkins JN, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Swain SM, Mamounas EP, Wolmark N. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012 Jan 26;366(4):310-20. doi: 10.1056/NEJMoa1111097.

Bear HD, Tang G, Rastogi P, et al.: The effect on pCR of bevacizumab and/or antimetabolites added to standard neoadjuvant chemotherapy: NSABP protocol B-40. [Abstract] J Clin Oncol 29 (Suppl 15): A-LBA1005, 2011.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bear HD, Tang G, Rastogi P, Geyer CE Jr, Liu Q, Robidoux A, Baez-Diaz L, Brufsky AM, Mehta RS, Fehrenbacher L, Young JA, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Costantino JP, Paik S, Swain SM, Mamounas EP, Wolmark N. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1037-1048. doi: 10.1016/S1470-2045(15)00041-8. Epub 2015 Aug 10. Erratum In: Lancet Oncol. 2015 Dec;16(16):e589.

• Responsible Party: NSABP Foundation Inc
• ClinicalTrials.gov Identifier: NCT00408408
• Other Study ID Numbers: NSABP B-40; NSABP B-40
• First Submitted: December 6, 2006
• First Posted: December 7, 2006
• Results First Submitted: March 23, 2017
• Results First Posted: September 18, 2017
• Last Update Posted: September 18, 2017