Status unknownNCT00408408Updated Sep 18, 2017Results posted

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 Phase 3 interventional study of bevacizumab and capecitabine in Breast Cancer, sponsored by NSABP Foundation Inc. Status unknown at 442 sites in 3 countries. Open to female participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2017-09-18.

Sponsored by NSABP Foundation Inc · Phase 3, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Sep 2017), so the status shown — last known as Active, not recruiting — may be out of date.

Phase: Phase 3
Study type: Interventional
Enrollment: 1,206
Allocation: Randomized
Ages: 18 Years to 120 Years
Sex: Female

Study 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.

Read the 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 studied

Breast Cancer

Browse trials for

Breast Neoplasms 12,544

Keywords

stage I breast cancer
stage II breast cancer
stage IIIA breast cancer

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 1,206 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

NSABP Foundation Inc is the lead sponsor of 64 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 120 Years
Sexes eligible: Female
Accepts healthy volunteers: No

Inclusion criteria

The patient must have consented to participate and must have signed and dated an appropriate Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines for the study treatment and submission of pre-entry core biopsy material for correlative studies.
Patients must be female.
Patients must be 18 years of age or older.
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.
The primary breast tumor must be palpable and measure greater than or equal to 2.0 cm on physical exam.
All patients must have their left ventricular ejection fraction (LVEF) assessed by multigated acquisition (MUGA) scan or echocardiogram within 3 months prior to study entry. The LVEF must be greater than or equal to the lower limit of normal (LLN) for the cardiac imaging facility performing the study. Note: If the cardiac imaging facility cannot provide a LLN, use 50% as the LLN value.
- Note: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments to determine if bevacizumab therapy can be continued, it is critical that this baseline study be an accurate assessment of the patient's LVEF. If the baseline LVEF is greater than 75%, the investigator should have the study reviewed for accuracy prior to study entry. Following study entry, the LVEF determination may be reviewed up until the time of the post-chemotherapy (preoperative) evaluation. Please note that if a more accurate value is obtained from the review of the baseline MUGA or echocardiogram, the correct value must be submitted to the NSABP before the post-chemotherapy (preoperative) MUGA or echocardiogram is performed or it cannot be used for managing postoperative bevacizumab.
All patients must have an EKG within 3 months prior to study entry.
At the time of randomization:
- Absolute neutrophil count (ANC) must be greater than or equal to 1200/mm3.
- Platelet count must be greater than or equal to 100,000/mm3.
- Hemoglobin must be greater than or equal to 10 g/dL.
- There must be evidence of adequate hepatic function by these criteria:
- Total bilirubin must be less than or equal to the ULN for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) resulting from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
- Alkaline phosphatase must be less than or equal 2.5 x ULN for the lab; and
- Aspartate Aminotransferase (AST) must be less than or equal to 1.5 x ULN for the lab.
- Alkaline phosphatase and AST may not both be greater than the ULN. For example, if the alkaline phosphatase is greater than the ULN but less than or equal 2.5 x ULN, then the AST must be less than or equal the ULN. If the AST is greater than the ULN but less than or equal 1.5 x ULN, then the alkaline phosphatase must be less than or equal ULN.
Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal 2.5 x ULN are eligible for inclusion in the study if bone scans do not demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging does not demonstrate metastatic disease and adequate bone marrow and liver function results as described above are met.
The following criteria for evidence of adequate renal function must be met:
Serum creatinine less than or equal ULN for the lab.
Calculated creatinine clearance must be greater than 50 mL/min.
Urine protein/urine creatinine (UPC) ratio must be less than 1.0.
Patient must be able to swallow oral medications.

Exclusion criteria

Exclusion criteria:

Tumor determined to be strongly human epidermal growth factor receptor 2 (HER2)-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification).
Excisional or incisional biopsy for this primary breast tumor.
Surgical axillary staging procedure prior to study entry. Exceptions: 1) Fine Needle Aspiration (FNA) or core biopsy of an axillary node is permitted for any patient, and 2) although not recommended, a pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes is permitted.
Tumors clinically staged as T4.
Ipsilateral cN2b or cN3 disease. (Patients with cN1 or cN2a disease are eligible.)
Definitive clinical or radiologic evidence of metastatic disease.
Synchronous bilateral breast cancer (invasive or DCIS).
Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry.
Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to randomization.)
Therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention. (Patients are eligible only if these medications are discontinued prior to randomization.)
Prior history of breast cancer, including DCIS. (Patients with a history of lobular carcinoma in situ [LCIS] are eligible.)
Prior therapy with anthracyclines, taxanes, capecitabine, 5-FU (fluorouracil), gemcitabine, or bevacizumab for any malignancy.
Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by her physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
Cardiac disease that would preclude the use of anthracyclines. This includes:
- angina pectoris that requires the use of anti-anginal medication;
- history of documented congestive heart failure;
- serious cardiac arrhythmia requiring medication;
- severe conduction abnormality;
- valvular disease with documented cardiac function compromise; and
- uncontrolled hypertension defined as BP greater than 150/90 on antihypertensive therapy. (Patients with hypertension that is well controlled on medication are eligible.)
History of myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function.
History of transient ischemic attack (TIA) or cerebrovascular accident (CVA).
History of other arterial thrombotic event within 12 months before study entry.
Symptomatic peripheral vascular disease.
Any significant non-traumatic bleeding within 6 months before study entry.
Serious or non-healing wound, skin ulcers, or incompletely healed bone fracture.
Gastroduodenal ulcer(s) determined by endoscopy to be active.
Invasive procedures defined as follows:
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to planned start of study therapy. (Note: Placement of a vascular access device is not considered a major surgical procedure.)
- Anticipation of need for major surgical procedures (other than the required breast surgery) during the course of the study.
Known bleeding diathesis or coagulopathy. (Patients on warfarin with an in-range international normalized ratio [INR] [usually between 2 and 3] are eligible.)
Sensory/motor neuropathy greater than or equal grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0).
Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude treatment with any of the treatment regimens or would prevent required follow-up.
Conditions that would prohibit administration of corticosteroids.
History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.
Administration of any investigational agents within 30 days before study entry.
Pregnancy or lactation at the time of proposed randomization.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 1,206 participants (actual)

Study arms

Active comparator
Arm 1A: Docetaxel then AC
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).
Drug: cyclophosphamide · Drug: docetaxel · Drug: doxorubicin hydrochloride (Adriamycin)
Experimental
Arm 1B Docetaxel + Bev then AC + Bev
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.
Biological: bevacizumab · Drug: cyclophosphamide · Drug: docetaxel · Drug: doxorubicin hydrochloride (Adriamycin)
Experimental
Arm 2A: Docetaxel + Capecitabine then AC
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.
Drug: capecitabine · Drug: cyclophosphamide · Drug: docetaxel · Drug: doxorubicin hydrochloride (Adriamycin)
Experimental
Arm 2B: Docetaxel + Cape + Bev then AC + Bev
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.
Biological: bevacizumab · Drug: capecitabine · Drug: cyclophosphamide · Drug: docetaxel · Drug: doxorubicin hydrochloride (Adriamycin)
Experimental
Arm 3A: Docetaxel + Gem then AC
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.
Drug: cyclophosphamide · Drug: docetaxel · Drug: doxorubicin hydrochloride (Adriamycin) · Drug: gemcitabine hydrochloride
Experimental
Arm 3B: Docetaxel + Gem + Bev then AC + Bev
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.
Biological: bevacizumab · Drug: cyclophosphamide · Drug: docetaxel · Drug: doxorubicin hydrochloride (Adriamycin) · Drug: gemcitabine hydrochloride

Interventions

Biologicalbevacizumab
15 mg/kg IV
Drugcapecitabine
825 mg/m2 orally
Drugcyclophosphamide
600 mg/m2 IV
Drugdocetaxel
100 mg/m2 IV
Drugdoxorubicin hydrochloride (Adriamycin)
60 mg/m2 IV
Druggemcitabine hydrochloride
1000 mg/m2 IV

What researchers measure

Primary outcomes

Pathologic Complete Response (pCR) of the Primary Tumor in the Breast
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

Secondary outcomes

pCR in the Breast and Nodes
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
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
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
Clinical Overall Response: cOR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens
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
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
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
Clinical Complete Resonse: cCR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens
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
Percentage of Cardiac Events
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.
Surgical Complication
Number of patients with Grade 4 or above surgery-related toxicities
Time frame: 24 months after study entry
Toxicities Including Events Other Than Congestive Heart Failure, of Chemotherapy Alone, Bevacizumab With Chemotherapy, and Bevacizumab Alone
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
Disease-free Survival (DFS)
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

Results

Posted Sep 18, 2017

Participant flow

Participant flow — Overall Study
Milestone	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
Started	201	199	204	201	197	204
Completed	199	196	204	194	192	201
Not completed	2	3	0	7	5	3
Withdrew: No follow up data	2	3	0	7	5	3

Outcome measures

PrimaryPathologic Complete Response (pCR) of the Primary Tumor in the Breast

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
Reported as:: Number · percentage of patients

Pathologic Complete Response (pCR) of the Primary Tumor in the Breast
percentage of patients	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
Pathologic Complete Response (pCR) of the Primary Tumor in the Breast	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)

SecondarypCR in the Breast and Nodes

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
Reported as:: Number · percentage of patients

pCR in the Breast and Nodes
percentage of patients	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
pCR in the Breast and Nodes	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)

SecondaryClinical 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

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
Reported as:: Number · percentage of patients

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
percentage of patients	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
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	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)

SecondaryClinical Overall Response: cOR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens

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
Reported as:: Number · percentage of patients

Clinical Overall Response: cOR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens
percentage of patients	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
Clinical Overall Response: cOR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens	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)

SecondaryClinical 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

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
Reported as:: Number · percentage of patients

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
percentage of patients	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
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	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)

SecondaryClinical Complete Resonse: cCR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens

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
Reported as:: Number · percentage of patients

Clinical Complete Resonse: cCR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens
percentage of patients	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
Clinical Complete Resonse: cCR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens	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)

SecondaryPercentage of Cardiac Events

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.

Results for this outcome have not been posted.

SecondarySurgical Complication

Number of patients with Grade 4 or above surgery-related toxicities

Time frame:: 24 months after study entry
Reported as:: Number · participants

Surgical Complication
participants	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
Surgical Complication	1	1	0	1	0	1

SecondaryToxicities Including Events Other Than Congestive Heart Failure, of Chemotherapy Alone, Bevacizumab With Chemotherapy, and Bevacizumab Alone

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
Reported as:: Number · participants

Toxicities Including Events Other Than Congestive Heart Failure, of Chemotherapy Alone, Bevacizumab With Chemotherapy, and Bevacizumab Alone
participants	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
Toxicities Including Events Other Than Congestive Heart Failure, of Chemotherapy Alone, Bevacizumab With Chemotherapy, and Bevacizumab Alone	180	157	172	185	158	185

SecondaryDisease-free Survival (DFS)

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
Reported as:: Number · percentage of patients

Disease-free Survival (DFS)
percentage of patients	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
Disease-free Survival (DFS)	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

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Docetaxel Then AC	—	4/199 (2%)	118/199 (59.3%)
Docetaxel + Bev Then AC + Bev	—	15/196 (7.7%)	150/196 (76.5%)
Docetaxel + Capecitabine Then AC	—	8/203 (3.9%)	168/203 (82.8%)
Docetaxel + Cape + Bev Then AC + Bev	—	30/196 (15.3%)	182/196 (92.9%)
Docetaxel + Gem Then AC	—	2/194 (1%)	150/194 (77.3%)
Docetaxel + Gem + Bev Then AC + Bev	—	15/202 (7.4%)	178/202 (88.1%)

Most frequent serious events

Showing 10 of 48

Most frequent serious events
Event	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
Left ventricular systolic dysfunctionCardiac disorders	0/199	1/196	1/203	5/196	0/194	2/202
ProteinuriaRenal and urinary disorders	0/199	4/196	0/203	0/196	0/194	1/202
Thromboembolic eventVascular disorders	1/199	1/196	2/203	4/196	0/194	1/202
Wound dehiscenceInjury, poisoning and procedural complications	0/199	2/196	0/203	3/196	0/194	2/202
DyspneaRespiratory, thoracic and mediastinal disorders	0/199	0/196	0/203	2/196	0/194	1/202
HypokalemiaMetabolism and nutrition disorders	2/199	0/196	0/203	2/196	1/194	1/202
DehydrationMetabolism and nutrition disorders	0/199	0/196	0/203	0/196	0/194	2/202
Nervous system disorders - Other, specifyNervous system disorders	0/199	0/196	0/203	1/196	0/194	2/202
Creatinine increasedInvestigations	0/199	0/196	0/203	0/196	1/194	0/202
Infections and infestations - Other, specifyInfections and infestations	0/199	0/196	0/203	0/196	1/194	0/202

Most frequent other events

Showing 10 of 22

Most frequent other events
Event	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
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders	13/199	32/196	92/203	110/196	5/194	14/202
Mucositis oralGastrointestinal disorders	22/199	54/196	56/203	83/196	38/194	58/202
Neutrophil count decreasedInvestigations	28/199	30/196	42/203	37/196	64/194	70/202
DiarrheaGastrointestinal disorders	26/199	27/196	52/203	43/196	41/194	43/202
HypertensionVascular disorders	4/199	49/196	3/203	43/196	2/194	49/202
Peripheral sensory neuropathyNervous system disorders	33/199	35/196	29/203	40/196	19/194	21/202
Rash maculo-papularSkin and subcutaneous tissue disorders	22/199	22/196	11/203	29/196	33/194	38/202
Alanine aminotransferase increased (ALT/SGPT)Investigations	2/199	9/196	10/203	7/196	26/194	35/202
Aspartate aminotransferase increased (AST/SGOT)Investigations	3/199	7/196	5/203	8/196	18/194	27/202
Febrile neutropeniaBlood and lymphatic system disorders	5/199	18/196	14/203	23/196	16/194	19/202

Baseline characteristics

Age, Continuous
Age, Continuous(years)	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
Mean	48 ± 9.1	49 ± 9.6	49 ± 9.8	49 ± 10.4	48 ± 9.9	48 ± 9.8	48 ± 9.7

Sex: Female, Male
Sex: Female, Male(Participants)	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
Female	201	199	204	201	197	204	1206
Male	0	0	0	0	0	0	0

Study locations

442 sites

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205, United States
East Bay Radiation Oncology Center
Castro Valley, California 94546, United States
Eden Medical Center
Castro Valley, California 94546, United States
Valley Medical Oncology Consultants - Castro Valley
Castro Valley, California 94546, United States
Kaiser Permanente - Fremont
Fremont, California 94538, United States
Valley Medical Oncology
Fremont, California 94538, United States
Cancer Care Associates
Fresno, California 93720, United States
Kaiser Permanente Medical Center - Hayward
Hayward, California 94545, United States
Scripps Cancer Center - San Diego
La Jolla, California 92037, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California 92354, United States
Contra Costa Regional Medical Center
Martinez, California 94553-3156, United States
El Camino Hospital Cancer Center
Mountain View, California 94040, United States
Highland General Hospital
Oakland, California 94602, United States
Alta Bates Summit Medical Center - Summit Campus
Oakland, California 94609, United States
Bay Area Breast Surgeons, Incorporated
Oakland, California 94609, United States
CCOP - Bay Area Tumor Institute
Oakland, California 94609, United States
Larry G Strieff MD Medical Corporation
Oakland, California 94609, United States
Tom K Lee, Incorporated
Oakland, California 94609, United States
Kaiser Permanente Medical Center - Oakland
Oakland, California 94611, United States
St. Joseph Hospital Regional Cancer Center - Orange
Orange, California 92868, United States
Desert Regional Medical Center Comprehensive Cancer Center
Palm Springs, California 92262, United States
Valley Care Medical Center
Pleasanton, California 94588, United States
Valley Medical Oncology Consultants - Pleasanton
Pleasanton, California 94588, United States
Kaiser Permanente Medical Center - Redwood City
Redwood City, California 94063, United States
Kaiser Permanente Medical Center - Richmond
Richmond, California 94801, United States
Kaiser Permanente Medical Center - Roseville
Roseville, California 95661, United States
South Sacramento Kaiser-Permanente Medical Center
Sacramento, California 95823, United States
Kaiser Permanente Medical Center - Sacramento
Sacramento, California 95825, United States
Salinas Valley Memorial Hospital
Salinas, California 93901, United States
Kaiser Permanente Medical Office -Vandever Medical Office
San Diego, California 92120, United States
Kaiser Permanente Medical Center - San Francisco Geary Campus
San Francisco, California 94115, United States
Kaiser Permanente Medical Center - Santa Teresa
San Jose, California 95119, United States
Doctors Medical Center - San Pablo Campus
San Pablo, California 94806, United States
Kaiser Foundation Hospital - San Rafael
San Rafael, California 94903, United States
Kaiser Permanente Medical Center - Santa Clara Kiely Campus
Santa Clara, California 95051, United States
Kaiser Permanente Medical Center - Santa Rosa
Santa Rosa, California 95403, United States
Kaiser Permanente Medical Center - South San Francisco
South San Francisco, California 94080, United States
Kaiser Permanente Medical Facility - Stockton
Stockton, California 95210, United States
Kaiser Permanente Medical Center - Vallejo
Vallejo, California 94589, United States
Kaiser Permanente Medical Center - Walnut Creek
Walnut Creek, California 94596, United States
Aurora Presbyterian Hospital
Aurora, Colorado 80012, United States
Boulder Community Hospital
Boulder, Colorado 80301-9019, United States
Memorial Hospital Cancer Center - Colorado Springs
Colorado Springs, Colorado 80909, United States
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado 80933, United States
St. Anthony Central Hospital
Denver, Colorado 80204, United States
Kaiser Permanente - Denver
Denver, Colorado 80205, United States
Porter Adventist Hospital
Denver, Colorado 80210, United States
Presbyterian - St. Luke's Medical Center
Denver, Colorado 80218, United States
St. Joseph Hospital
Denver, Colorado 80218, United States
Rose Medical Center
Denver, Colorado 80220, United States
CCOP - Colorado Cancer Research Program
Denver, Colorado 80224-2522, United States
Swedish Medical Center
Englewood, Colorado 80110, United States
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
Grand Junction, Colorado 81502, United States
North Colorado Medical Center
Greeley, Colorado 80631, United States
Kaiser Permanente - Lafayette
Lafayette, Colorado 80026, United States
Sky Ridge Medical Center
Lone Tree, Colorado 80124, United States
Hope Cancer Care Center at Longmont United Hospital
Longmont, Colorado 80501, United States
McKee Medical Center
Loveland, Colorado 80539, United States
St. Mary - Corwin Regional Medical Center
Pueblo, Colorado 81004, United States
North Suburban Medical Center
Thornton, Colorado 80229, United States
Exempla Lutheran Medical Center
Wheat Ridge, Colorado 80033, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
Farmington, Connecticut 06360-2875, United States
Helen and Harry Gray Cancer Center at Hartford Hospital
Hartford, Connecticut 06102-5037, United States
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
Hartford, Connecticut 06105, United States
Eastern Connecticut Hematology and Oncology Associates
Norwich, Connecticut 06360, United States
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware 19958, United States
CCOP - Christiana Care Health Services
Newark, Delaware 19713, United States
Sibley Memorial Hospital
Washington, D.C., District of Columbia 20016, United States
Herbert D. Kerman Regional Oncology Center - Daytona Beach
Daytona Beach, Florida 32114, United States
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
Fort Lauderdale, Florida 33308, United States
Broward General Medical Center Cancer Center
Fort Lauderdale, Florida 33316, United States
Baptist Cancer Institute - Jacksonville
Jacksonville, Florida 32207, United States
Ella Milbank Foshay Cancer Center at Jupiter Medical Center
Jupiter, Florida 33458, United States
CCOP - Mount Sinai Medical Center
Miami Beach, Florida 33140, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida 32803-1273, United States
M.D. Anderson Cancer Center at Orlando
Orlando, Florida 32806, United States
Phoebe Cancer Center at Phoebe Putney Memorial Hospital
Albany, Georgia 31701, United States
Northeast Georgia Medical Center
Gainesville, Georgia 30501, United States
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Savannah, Georgia 31403-3089, United States
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
Savannah, Georgia 31405, United States
Kapiolani Medical Center at Pali Momi
'Aiea, Hawaii 96701, United States
Cancer Research Center of Hawaii
Honolulu, Hawaii 96813, United States
OnCare Hawaii, Incorporated - Lusitana
Honolulu, Hawaii 96813, United States
Queen's Cancer Institute at Queen's Medical Center
Honolulu, Hawaii 96813, United States
Straub Clinic and Hospital, Incorporated
Honolulu, Hawaii 96813, United States
Hawaii Medical Center - East
Honolulu, Hawaii 96817, United States
OnCare Hawaii, Incorporated - Kuakini
Honolulu, Hawaii 96817, United States
Kaiser Permanente - Moanalua Medical Center and Clinic
Honolulu, Hawaii 96819, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii 96826, United States
Maui Memorial Medical Center
Wailuku, Hawaii 96793, United States
Pacific Cancer Institute - Maui
Wailuku, Hawaii 96793, United States
Kootenai Cancer Center - Coeur d'Alene
Coeur d'Alene, Idaho 83814, United States
Saint Anthony's Hospital at Saint Anthony's Health Center
Alton, Illinois 62002, United States
Illinois CancerCare - Bloomington
Bloomington, Illinois 61701, United States
St. Joseph Medical Center
Bloomington, Illinois 61701, United States
Graham Hospital
Canton, Illinois 61520, United States
Illinois CancerCare - Canton
Canton, Illinois 61520, United States
Illinois CancerCare - Carthage
Carthage, Illinois 62321, United States
Memorial Hospital
Carthage, Illinois 62321, United States
Mount Sinai Hospital Medical Center
Chicago, Illinois 60608, United States

Showing the first 100 of 442 sites across 3 countries.

References and documents

Publications

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. PubMed 22276821 ↗
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.
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. doi: 10.1016/S1470-2045(15)00468-4. PubMed 26272770 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 18, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00408408
Lead sponsor: NSABP Foundation Inc
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Dec 7, 2006
Start date: Nov 2006
Primary completion: Mar 2011
Completion: Mar 2018 (estimated)
Results posted: Sep 18, 2017
Last update: Sep 18, 2017

Study contacts

Norman Wolmark, MD

principal investigator · NSABP Foundation Inc

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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