Trial Outcomes & Findings for Therapy With Bevacizumab (BEV), Doxorubicin, and Cyclophosphamide Followed by BEV, Docetaxel, and Capecitabine Before Surgery Followed by BEV Alone After Surgery for Women With Locally Advanced Breast Cancer (NCT NCT00365417)

NCT ID: NCT00365417

Last Updated: 2021-04-13

Results Overview

Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 45 participants
• Primary outcome timeframe: Approximately 7 months
• Results posted on: 2021-04-13

Participant Flow

Participant milestones

Measure	Chemo Plus Bevacizumab Bevacizumab beginning concurrently with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy followed by postoperative bevacizumab alone for women with HER2 negative locally advanced breast cancer
Overall Study STARTED	45
Overall Study COMPLETED	45
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Therapy With Bevacizumab (BEV), Doxorubicin, and Cyclophosphamide Followed by BEV, Docetaxel, and Capecitabine Before Surgery Followed by BEV Alone After Surgery for Women With Locally Advanced Breast Cancer

Baseline characteristics by cohort

Measure	Chemo Plus Bevacizumab n=45 Participants Bevacizumab beginning concurrently with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy followed by postoperative bevacizumab alone for women with HER2 negative locally advanced breast cancer
Age, Customized 18 to less than 50 years	19 participants n=5 Participants
Age, Customized Between 50 and 59 years	13 participants n=5 Participants
Age, Customized Greater than 59 years	13 participants n=5 Participants
Age, Continuous	51.8 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized White	43 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	3 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	42 participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 7 months

Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen

Outcome measures

Measure	Neoadjuvant Study Treatment n=45 Participants Doxorubicin, cyclophosphamide, and bevacizumab followed by docetaxel and capecitabine
Pathologic Complete Response (pCR) in the Breast pCR in the breast	4 participants
Pathologic Complete Response (pCR) in the Breast No pCR in the breast	38 participants
Pathologic Complete Response (pCR) in the Breast No data available	3 participants

SECONDARY outcome

Timeframe: Approximately 7 months

Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel nodes

Outcome measures

Measure	Neoadjuvant Study Treatment n=45 Participants Doxorubicin, cyclophosphamide, and bevacizumab followed by docetaxel and capecitabine
pCR in the Breast and Nodes pCR in the breast and nodes	4 participants
pCR in the Breast and Nodes No pCR in the breast and nodes	38 participants
pCR in the Breast and Nodes No data available	3 participants

SECONDARY outcome

Timeframe: Approximately 6 months

Clinical tumor measurements were required before study entry & before cycle 5 of chemotherapy (between AC & TX). Final tumor measurements were obtained 4-5 weeks after the last dose of chemotherapy. Clinical tumor assessments by physical examination were recommended before each chemotherapy cycle. The criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee(RECIST) were used to define clinical response status. CR was defined as the disappearance of all lesions with no evidence of PD. PR was defined as at least 30% decrease in the sum of the longest diameter of target lesions, using as reference the baseline sum longest diameter and/or the persistence of greater than or equal to 1 nontarget lesion without worsening of any other clinical manifestations of disease. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions, or unequivocal progression of existing lesions.

Outcome measures

Measure	Neoadjuvant Study Treatment n=45 Participants Doxorubicin, cyclophosphamide, and bevacizumab followed by docetaxel and capecitabine
Clinical Response Rate (cRR) of the Sequential Regimen	77.27 percentage of patients Interval 62.16 to 88.53

SECONDARY outcome

Timeframe: Approximately 14 months

Number of Adverse Events

Outcome measures

Measure	Neoadjuvant Study Treatment n=45 Participants Doxorubicin, cyclophosphamide, and bevacizumab followed by docetaxel and capecitabine
Reported Adverse Events	566 events

SECONDARY outcome

Timeframe: Assessments throughout; up to 18 months following study entry

Population: Symptomatic cardiac toxicity was not observed in this study.

Events: Congestive Heart Failure; Cardiac Death

Outcome measures

Measure	Neoadjuvant Study Treatment n=45 Participants Doxorubicin, cyclophosphamide, and bevacizumab followed by docetaxel and capecitabine
Cardiac Events	0 cardiac events

SECONDARY outcome

Timeframe: 2 years

Percentage of patients free from disease progression. Progression is determined using international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. At least a 20% increase in the sum of the longest diameter of the target lesions. Other manifestations of progressive disease would also be classified as disease progression, eg., appearance of one or more new lesions in the breast, regional lymph nodes or distant sites, unequivocal progression of existing non-target lesions, and appearance of inflammatory carcinoma on clinical exam.

Outcome measures

Measure	Neoadjuvant Study Treatment n=45 Participants Doxorubicin, cyclophosphamide, and bevacizumab followed by docetaxel and capecitabine
Progression-free Survival	57.69 percentage of patients Interval 42.0 to 70.56

SECONDARY outcome

Timeframe: 2 years

Percentage of patients alive.

Outcome measures

Measure	Neoadjuvant Study Treatment n=45 Participants Doxorubicin, cyclophosphamide, and bevacizumab followed by docetaxel and capecitabine
Overall Survival	74.52 percentage of patients Interval 58.5 to 85.09

SECONDARY outcome

Timeframe: Two (2) years

Population: Of the 45 patients, 43 patients had surgery and therefore 43 patients in this outcome.

Number of patients with at least one surgical complications (wound dehiscence, infection, seroma, or hematoma)

Outcome measures

Measure	Neoadjuvant Study Treatment n=43 Participants Doxorubicin, cyclophosphamide, and bevacizumab followed by docetaxel and capecitabine
Number of Patients With at Least One Surgical Complications (Wound Dehiscence, Infection, Seroma, or Hematoma).	24 participants

Adverse Events

Chemo Plus Bevacizumab

Serious events: 14 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	Chemo Plus Bevacizumab n=45 participants at risk Bevacizumab beginning concurrently with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy followed by postoperative bevacizumab alone for women with HER2 negative locally advanced breast cancer
Gastrointestinal disorders Diarrhea	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Respiratory, thoracic and mediastinal disorders Dyspnea	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Esophagitis	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Skin and subcutaneous tissue disorders Hand-foot	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Blood and lymphatic system disorders Hemoglobin	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Metabolism and nutrition disorders Hypokalemia	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection - blood	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection - catheter related	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection - lung (pneumonia)	4.4% 2/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection - skin (cellulites)	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection - ungual (nails)	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection - urinary tract NOS	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection with normal ANC - sinus	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection with normal ANC - skin (cellulites)	4.4% 2/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection with normal ANC - upper airway NOS	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection with normal ANC - urinary tract NOS	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection with normal ANC - wound	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
General disorders Insomnia	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Mucositis (clinical exam) - oral cavity	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Mucositis (functional/symptomatic) - esophagus	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Mucositis (functional/symptomatic) - oral cavity	4.4% 2/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - abdominal NOS	4.4% 2/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - back	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - musculoskeletal (hip)	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
General disorders Syncope (fainting)	2.2% 1/45 • Assessments throughout up to 3 years, 3 months
Vascular disorders Thrombosis/thrombus/embolism	4.4% 2/45 • Assessments throughout up to 3 years, 3 months

Other adverse events

Measure	Chemo Plus Bevacizumab n=45 participants at risk Bevacizumab beginning concurrently with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy followed by postoperative bevacizumab alone for women with HER2 negative locally advanced breast cancer
Investigations ALT	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Skin and subcutaneous tissue disorders Alopecia	77.8% 35/45 • Assessments throughout up to 3 years, 3 months
General disorders Anorexia	33.3% 15/45 • Assessments throughout up to 3 years, 3 months
Investigations Blood - other HCT	11.1% 5/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Constipation	13.3% 6/45 • Assessments throughout up to 3 years, 3 months
General disorders Cytokine release syndrome	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Dehydration	20.0% 9/45 • Assessments throughout up to 3 years, 3 months
Skin and subcutaneous tissue disorders Dermatitis - radiation	20.0% 9/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Diarrhea	33.3% 15/45 • Assessments throughout up to 3 years, 3 months
Nervous system disorders Dizziness	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Dysphagia	15.6% 7/45 • Assessments throughout up to 3 years, 3 months
Respiratory, thoracic and mediastinal disorders Dyspnea	13.3% 6/45 • Assessments throughout up to 3 years, 3 months
General disorders Fatigue	71.1% 32/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Febrile neutropenia	24.4% 11/45 • Assessments throughout up to 3 years, 3 months
Skin and subcutaneous tissue disorders Hand-foot	57.8% 26/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Heartburn	20.0% 9/45 • Assessments throughout up to 3 years, 3 months
Blood and lymphatic system disorders Hemaglobin	26.7% 12/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Hemorrhoids	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
Endocrine disorders Hot flashes	24.4% 11/45 • Assessments throughout up to 3 years, 3 months
Investigations Hyperglycemia	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
Cardiac disorders Hypertension	24.4% 11/45 • Assessments throughout up to 3 years, 3 months
Investigations Hypocalcemia	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Investigations Hypokalemia	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
Investigations Hypophosphatemia	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection (documented clincally) - upper airway NOS	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection - bladder (urinary)	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection - other (thrush)	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection with normal ANC - bladder (urinary)	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection with normal ANC - pharynx	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Infections and infestations Infection with normal ANC - skin (cellulites)	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
General disorders Insomnia	13.3% 6/45 • Assessments throughout up to 3 years, 3 months
Reproductive system and breast disorders Irregular menses	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
Cardiac disorders Left ventricular systolic function	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Blood and lymphatic system disorders Leukocytes	31.1% 14/45 • Assessments throughout up to 3 years, 3 months
Investigations Lymphopenia	40.0% 18/45 • Assessments throughout up to 3 years, 3 months
Psychiatric disorders Mood Alteration	11.1% 5/45 • Assessments throughout up to 3 years, 3 months
Psychiatric disorders Mood alteration - anxiety	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Mucositis (clinical exam) - oral cavity	28.9% 13/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Mucositis - oral cavity	71.1% 32/45 • Assessments throughout up to 3 years, 3 months
General disorders Muscle weakness - whole body/generalized	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
Skin and subcutaneous tissue disorders Nail changes	15.6% 7/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Nausea	28.9% 13/45 • Assessments throughout up to 3 years, 3 months
Nervous system disorders Neuropathy - motor	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Nervous system disorders Neuropathy - sensory	15.6% 7/45 • Assessments throughout up to 3 years, 3 months
Blood and lymphatic system disorders Neutrophils	26.7% 12/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - abdominal NOS	13.3% 6/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - back	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - bone	24.4% 11/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - chest/thorax	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - extremity-limb	20.0% 9/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - head/headache	24.4% 11/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - joint	17.8% 8/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - muscle	24.4% 11/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - oral cavity	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - pain NOS	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
General disorders Pain - throat/pharynx/larynx	8.9% 4/45 • Assessments throughout up to 3 years, 3 months
Skin and subcutaneous tissue disorders Rash	22.2% 10/45 • Assessments throughout up to 3 years, 3 months
Cardiac disorders Supraventricular arrhythmia - sinus tachycardia	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
General disorders Sweating	6.7% 3/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Taste alteration	20.0% 9/45 • Assessments throughout up to 3 years, 3 months
Gastrointestinal disorders Vomiting	22.2% 10/45 • Assessments throughout up to 3 years, 3 months
General disorders Weight loss	24.4% 11/45 • Assessments throughout up to 3 years, 3 months

Additional Information

Diana Gosik

NSABP Foundation, Inc.

Phone: 412-339-5333

Email: diana.gosik@nsabp.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60