Neoplasms

Skin and Connective Tissue Diseases

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Breast Neoplasms

Inflammatory Breast Neoplasms

Breast Diseases

Skin Diseases

Inflammatory Breast Cancer

Antineoplastic Agents

All Drugs and Chemicals

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Trastuzumab

Cyclophosphamide

Bevacizumab

Docetaxel

Epirubicin

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Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

* Cohort A: Women with unresected locally advanced breast cancer (clinical Stage IIIA, IIIB, and IIIC)
* Cohort B: Women with resected pN2 or pN3 (pathologic Stage III) breast cancer

Both Cohorts: Epirubicin 90 mg/m2 IV every 21 days x 4 cycles

Both Cohorts: Cyclophosphamide 600 mg/m2 IV every 21 days x 4 cycles

Both Cohorts: Docetaxel 100 mg/m2 IV on Day 1 every 21 days x 4 cycles

Cohort A: Pre-op therapy - 4 mg/kg IV first dose, then subsequent doses at 2 mg/kg IV weekly (16+ weeks) until 1-7 days prior to surgery. Post-operative therapy (beginning no sooner than 28 days after surgery and continuing every 3 weeks x 13 doses) - 8 mg/kg IV first post-op dose, then subsequent doses at 6 mg/kg IV

Cohort B: 4 mg/kg IV first dose, then subsequent doses at 2 mg/kg IV weekly on days 1, 8, and 15. Three (3) weeks after last dose of docetaxel, 6 mg/kg IV and continuing every 3 weeks x 13 doses

Cohort A: Cycles 1-4, 15 mg/kg IV on day 1 of cycle 4 only; Cycles 5-7, 15 mg/kg IV on day 1 every 21 days x 3 cycles; post-operative therapy (beginning no sooner than 28 days after surgery), 15 mg/kg IV every 3 weeks x 13 doses

Cohort B: Cycles 5-8, 15 mg/kg IV on day 1 every 21 days x 4 cycles; beginning 3 weeks after last dose of docetaxel, 15 mg/kg IV every 3 weeks x 13 doses

Norman Wolmark, MD

The main purpose is to learn if adding bevacizumab to standard chemotherapy and trastuzumab to treat HER2-positive breast cancer will affect heart function. This study will evaluate:

* How bevacizumab, given with chemotherapy, and then bevacizumab given with trastuzumab after surgery, will affect breast tumors
* Side effects from adding bevacizumab to chemotherapy and trastuzumab
* Whether adding bevacizumab to chemotherapy and trastuzumab for breast cancer will affect the heart
* If receiving bevacizumab will have any effect on how patients recover from surgery

NSABP FB-5 is a Phase II study for women with HER2-positive invasive breast cancer evaluating a regimen of epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab and bevacizumab in two patient cohorts:

* Cohort A: Women with unresected locally advanced breast cancer (clinical Stage IIIA, IIIB, and IIIC)
* Cohort B: Women with resected pN2 or pN3 (pathologic Stage III) breast cancer.

The primary aims of the study are to determine the rate of cardiac events for all patients and the pCR rate in the breast and axillary lymph nodes for Cohort A. Cardiac events will be defined as NYHA Class III/IV congestive heart failure and cardiac death. For Cohort A, secondary aims of the study include determining the rate of pCR in the breast and the cCR rate following the neoadjuvant therapy. The secondary aims also include determining the value of the regimen in improving 5-year RFS and 5-year OS and determining the non-cardiac toxicities of the regimen in all patients.

Patients in Cohort A will receive neoadjuvant therapy consisting of epirubicin plus cyclophosphamide (EC) every 21 days for 4 cycles plus bevacizumab given on Day 1 of Cycle 4 only, followed by docetaxel every 21 days for 4 cycles plus bevacizumab every 21 days for the initial 3 cycles. Patients will also receive weekly trastuzumab beginning with the first cycle of docetaxel and continuing until 1-7 days before surgery. Patients will then have breast surgery (lumpectomy or mastectomy) with axillary staging. Approximately 4-6 weeks following surgery, bevacizumab and trastuzumab will resume and continue every 3 weeks for 13 doses to complete one year of targeted therapy.

Patients in Cohort B will receive adjuvant therapy consisting of EC every 21 days for 4 cycles followed by docetaxel every 21 days for 4 cycles. Beginning with the first cycle of docetaxel, patients will also receive bevacizumab every 21 days for 4 cycles and weekly trastuzumab until 3 weeks after the last docetaxel dose. Beginning 3 weeks after the last dose of docetaxel, both bevacizumab and trastuzumab will then be given every 3 weeks for 13 doses to complete 1 year of targeted therapy.

Cardiac monitoring will be conducted for both cohorts. For Cohort A, LVEF assessments will be conducted at baseline, post-EC, 2-4 weeks following surgery (about 6 months from study entry), and 9, 12, 15, and 18 months from study entry. For Cohort B, LVEF assessments will be conducted at baseline, post-EC, and 6, 9, 12, 15, and 18 months from study entry. The preferred method for LVEF assessment is 2-D echocardiogram; however, LVEF assessment by MUGA scan is permitted.

Patient follow-up will continue for 5 years following study entry.

The FB-5 sample size is 105 patients.

Therapy With Bevacizumab (BEV), Epirubicin, and Cyclophosphamide Followed by Docetaxel Plus Trastuzumab and BEV Given as Neoadjuvant or Adjuvant Therapy for Women With Locally Advanced HER2 Positive Invasive Breast Cancer

A Phase II Clinical Trial of Epirubicin Plus Cyclophosphamide Followed by Docetaxel Plus Trastuzumab and Bevacizumab Given as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or Given as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer

The determination of pCR is performed by the local pathologist following examination of tissue (breast and nodes)removed at the time of surgery. The outcome measure is the number of participants with no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or SNs identified after neoadjuvant chemotherapy.

The number of cardiac events defined as NYHA Class III/IV CHF and cardiac death.To determine the rate of cardiac events (NYHA Class III/IV CHF and cardiac death) of a regimen of EC followed by THA when administered to: Cohort A as neoadjuvant therapy for HER-2 positive locally advanced (clinical stage IIIA, IIIB or IIIC breast cancer or Cohort B as adjuvant therapy for resected HER2-positive pN2 or pN3 (pathologic stage III) breast cancer. The number of participants with one or more cardiac events are being reported.

The determination of pCR will be performed by the local pathologist following examination of tissue (breast and nodes) removed at the time of surgery.

cCR following the last dose of docetaxel (Cohort A). cCR is detemined by tumor measurement by physical exam at baseline: target lesions greater than or equal to 2.0 cm; non-target lesions greater than or equal to 2.0 cm. cCR assessment at other timepoints: resolution of all target and non-target lesions identified at baseline, and no new lesions or other signs of disease progression.

Death from any cause during the 5 years from study entry.

The percentage of patients with surgical complications (from mastectomy, lumpectomy, and axillary staging procedures).

Genentech, Inc.

International Drug Development Institute

NSABP Foundation Inc

• Cohort A: Women with unresected locally advanced breast cancer (clinical Stage IIIA, IIIB, and IIIC)

Cohort A

• Cohort B: Women with resected pN2 or pN3 (pathologic Stage III) breast cancer

Cohort B

Total

Age, Continuous

18 to less than 50 years

>=50 years and <=59 years

> 59 years

Age, Customized

Sex: Female, Male

White

Black or African American

Native Hawaiian or other Pacific Islander

American Indian or Alaskan Native

Asian

Unknown

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Director, Department of Site and Study Management

73 of the 76 patients in Cohort A were analyzed: 2 patients did not have surgery and 1 patient did not have the nodal status determined.

Number of Patients With Pathological Complete Response (pCR) in the Breast and Nodes for Patients With HER2-positive LABC Following Neoadjuvant Treatment (Cohort A)

Number of Participants With Cardiac Events

Number of Participants With no Histologic Evidence of Invasive Tumor Cells in the Surgical Breast Specimen.

* Cohort A: Women with unresected locally advanced breast cancer (clinical Stage IIIA, IIIB, and IIIC)
* Cohort B: Women with resected pN2 or pN3 (pathologic Stage III) breast cancer

Epirubicin: Both Cohorts: Epirubicin 90 mg/m2 IV every 21 days x 4 cycles

Cyclophosphamide: Both Cohorts: Cyclophosphamide 600 mg/m2 IV every 21 days x 4 cycles

Docetaxel: Both Cohorts: Docetaxel 100 mg/m2 IV on Day 1 every 21 days x 4 cycles

Trastuzumab: Cohort A: Pre-op therapy - 4 mg/kg IV first dose, then subsequent doses at 2 mg/kg IV weekly (16+ weeks) until 1-7 days prior to surgery. Post-operative therapy (beginning no sooner than 28 days after surgery and continuing every 3 weeks x 13 doses) - 8 mg/kg IV first post-op dose, then subsequent doses at 6 mg/kg IV

Cohort B: 4 mg/kg IV first dose, then subsequent doses at 2 mg/kg IV weekly on days 1, 8, and 15. Three (3) weeks after last dose of docetaxel, 6 mg/kg IV and continuing every 3 weeks x 13 doses

Bevacizumab: Cohort A: Cycles 1-4, 15 mg/kg IV on day 1 of cycle 4 only; Cycles 5-7, 15 mg/kg IV on day 1 every 21 days x 3 cycles; post-operative therapy (beginning no sooner than 28 days after surgery), 15 mg/kg IV every 3 weeks x 13 doses

Cohort B: Cycles 5-8, 15 mg/kg IV on day 1 every 21 days x 4 cycles; beginning 3 weeks after last dose of docetaxel, 15 mg/kg IV every 3 weeks x 13 doses

This outcome only applicable to Cohort A.

Clinical Complete Response (cCR)

Data shows total number of patients with 1 AE, for further information see Reported Adverse Events Section.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Therapy With Bevacizumab (BEV), Epirubicin, and Cyclophosphamide Followed by Docetaxel Plus Trastuzumab and BEV Given as Neoadjuvant or Adjuvant Therapy for Women With Locally Advanced HER2 Positive Invasive Breast Cancer	NCT00464646	Breast Cancer	Epirubicin Cyclophosphamid... Docetaxel Trastuzumab Bevacizumab	18 Years -	NSABP Foundation Inc
Therapy With Bevacizumab (BEV), Epirubicin, and Cyclophosphamide Followed by Docetaxel Plus Trastuzumab and BEV Given as Neoadjuvant or Adjuvant Therapy for Women With Locally Advanced HER2 Positive Invasive Breast Cancer	NCT00464646	Breast Cancer	Epirubicin Cyclophosphamid... Docetaxel Trastuzumab Bevacizumab	18 Years -	NSABP Foundation Inc

Spots Global Cancer Trial Database for pathologic stage iii breast cancer