NCT00408408|UnknownPhase 3ResultsDMC

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

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

NSABP Foundation Inc ClinicalTrials.gov

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1 other identifier

NSABP B-40

Study Type

interventional

Target

1,206

Locations

3 countries

Sites

442

Timeline

RegisteredDec 2006

StartedNov 2006

CompletionMar 2018

Brief 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.

Trial Health

At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

1,206

participants targeted

Target at P75+ for phase_3 breast-cancer

Timeline

Completed

Started Nov 2006

Longer than P75 for phase_3 breast-cancer

Geographic Reach

3 countries

442 active sites

Status

unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

11.3 years study duration

Study Start

First participant enrolled

November 1, 2006

Completed

1 month until next milestone

First Submitted

Initial submission to the registry

December 6, 2006

Completed

1 day until next milestone

First Posted

Study publicly available on registry

December 7, 2006

Completed

4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2011

Completed

6.6 years until next milestone

Results Posted

Study results publicly available

September 18, 2017

Completed

5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2018

Completed

Last Updated

September 18, 2017

Status Verified

September 1, 2017

Enrollment Period

4.3 years

First QC Date

December 6, 2006

Results QC Date

March 23, 2017

Last Update Submit

September 12, 2017

Conditions

Breast Cancer

Keywords

stage I breast cancerstage II breast cancerstage IIIA breast cancer

Outcome Measures

Primary Outcomes (1)

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 of surgery, on average 6 or 13 months

Secondary Outcomes (9)

pCR in the Breast and Nodes
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
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
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
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
Three to four weeks after the last chemotherapy dose, on average at 6 or 13 months
+4 more secondary outcomes

Study Arms (6)

Arm 1A: Docetaxel then AC

ACTIVE COMPARATOR

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: cyclophosphamideDrug: docetaxelDrug: doxorubicin hydrochloride (Adriamycin)

Arm 1B Docetaxel + Bev then AC + Bev

EXPERIMENTAL

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: bevacizumabDrug: cyclophosphamideDrug: docetaxelDrug: doxorubicin hydrochloride (Adriamycin)

Arm 2A: Docetaxel + Capecitabine then AC

EXPERIMENTAL

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: capecitabineDrug: cyclophosphamideDrug: docetaxelDrug: doxorubicin hydrochloride (Adriamycin)

Arm 2B: Docetaxel + Cape + Bev then AC + Bev

EXPERIMENTAL

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: bevacizumabDrug: capecitabineDrug: cyclophosphamideDrug: docetaxelDrug: doxorubicin hydrochloride (Adriamycin)

Arm 3A: Docetaxel + Gem then AC

EXPERIMENTAL

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: cyclophosphamideDrug: docetaxelDrug: doxorubicin hydrochloride (Adriamycin)Drug: gemcitabine hydrochloride

Arm 3B: Docetaxel + Gem + Bev then AC + Bev

EXPERIMENTAL

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: bevacizumabDrug: cyclophosphamideDrug: docetaxelDrug: doxorubicin hydrochloride (Adriamycin)Drug: gemcitabine hydrochloride

Interventions

bevacizumabBIOLOGICAL

15 mg/kg IV

Arm 1B Docetaxel + Bev then AC + BevArm 2B: Docetaxel + Cape + Bev then AC + BevArm 3B: Docetaxel + Gem + Bev then AC + Bev

capecitabineDRUG

825 mg/m2 orally

Arm 2A: Docetaxel + Capecitabine then ACArm 2B: Docetaxel + Cape + Bev then AC + Bev

cyclophosphamideDRUG

600 mg/m2 IV

Arm 1A: Docetaxel then ACArm 1B Docetaxel + Bev then AC + BevArm 2A: Docetaxel + Capecitabine then ACArm 2B: Docetaxel + Cape + Bev then AC + BevArm 3A: Docetaxel + Gem then ACArm 3B: Docetaxel + Gem + Bev then AC + Bev

docetaxelDRUG

100 mg/m2 IV

doxorubicin hydrochloride (Adriamycin)DRUG

60 mg/m2 IV

gemcitabine hydrochlorideDRUG

1000 mg/m2 IV

Arm 3A: Docetaxel + Gem then ACArm 3B: Docetaxel + Gem + Bev then AC + Bev

Eligibility Criteria

Age18 Years - 120 Years

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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
+8 more criteria

You may not qualify if:

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;
+22 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

NSABP Foundation Inclead
National Cancer Institute (NCI)collaborator

Study Sites (442)

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

East Bay Radiation Oncology Center

Castro Valley, California, 94546, United States

Location

Eden Medical Center

Castro Valley, California, 94546, United States

Location

Valley Medical Oncology Consultants - Castro Valley

Castro Valley, California, 94546, United States

Location

Kaiser Permanente - Fremont

Fremont, California, 94538, United States

Location

Valley Medical Oncology

Fremont, California, 94538, United States

Location

Cancer Care Associates

Fresno, California, 93720, United States

Location

Kaiser Permanente Medical Center - Hayward

Hayward, California, 94545, United States

Location

Scripps Cancer Center - San Diego

La Jolla, California, 92037, United States

Location

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Contra Costa Regional Medical Center

Martinez, California, 94553-3156, United States

Location

El Camino Hospital Cancer Center

Mountain View, California, 94040, United States

Location

Highland General Hospital

Oakland, California, 94602, United States

Location

Alta Bates Summit Medical Center - Summit Campus