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 | Completed Phase 2 Results

• 1 other identifier: NSABP FB-5
• Study Type: interventional
• Target: 105
• Locations: 2 countries
• Sites: 36

Brief Summary

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

Conditions

Breast Cancer

Keywords

NSABP; Epirubicin; Cyclophosphamide; Docetaxel; Trastuzumab; Bevacizumab; Neoadjuvant Therapy; HER2; Locally Advanced Breast Cancer; Adjuvant Therapy; Pathologic Stage III Breast Cancer; Inflammatory Breast Cancer

Outcome Measures

Primary Outcomes (2)

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

  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.

  Assessed at time of surgery on average at 8 months

• Number of Participants With Cardiac Events

  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.

  Cohort A: Baseline, post-treatment with EC, 2-4 weeks after surgery, and 9, 12, 15, and 18 months from study entry. Cohort B: Baseline, post-treatment with EC, 2-3 weeks after the last dose of docetaxel, and 6, 9, 12, 15, and 18 months from study entry.

Secondary Outcomes (6)

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

  Assessed at the time of surgery

• Clinical Complete Response (cCR)

  Determined at baseline, 2-3 weeks after the last EC dose, 2-4 weeks after last Docetaxel dose-before surgery.

• Grade 3 and 4 Toxicities, Including Toxicities Associated With Radiation Therapy(RT)

  Before each cycle of pre-op Rx; 2-4 wks after the last docetaxel dose; 2-4 wks post surgery (Cohort A); every 6 wks during post-op Rx (Cohort A); every 6 wks during targeted therapy alone (Cohort B); RT complications assessed at 12 mos from study entry

• Recurrence-free Survival

  From the first dose of study therapy until the date of recurrence or for a maximum of five (5) years from study entry

• Overall Survival

  From the first dose of study therapy until the date of death or for a maximum of five (5) years from study entry

Study Arms (1)

1

EXPERIMENTAL

* 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

Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Trastuzumab; Drug: Bevacizumab

Interventions

Epirubicin DRUG

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

Also known as: Ellence

1

Cyclophosphamide DRUG

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

1

Docetaxel DRUG

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

Also known as: Taxotere

1

Trastuzumab DRUG

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

Also known as: Herceptin

1

Bevacizumab DRUG

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

Also known as: Avastin

1

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Conditions for eligibility for patients with LABC (Cohort A):
• The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy or limited incisional biopsy.
• Patients must have clinical Stage IIIA, IIIB, or IIIC disease with a mass in the breast or axilla that is greater than or equal to 2.0 cm measured by clinical exam, unless the patient has inflammatory breast carcinoma, in which case measurable disease is not required.
• Conditions for eligibility for patients with resected Stage III breast cancer (Cohort B)
• Patients must have undergone either a total mastectomy or a lumpectomy.
• Patients must have completed one of the following procedures for evaluation of pathologic nodal status.
• Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes, or
• Axillary lymphadenectomy without SN isolation procedure.
• The interval between the last surgery (for breast cancer treatment or staging) and study entry must be no more than 84 days.
• By pathologic evaluation, ipsilateral nodes must be pN2 or pN3.
• For patients who undergo lumpectomy, the margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional operative procedures may be performed to obtain clear margins. If tumor is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. (Patients with margins positive for LCIS are eligible without additional resection.)
• For patients who undergo mastectomy, margins must be free of gross residual tumor. Patients with microscopic positive margins are eligible.
• Conditions for patient eligibility (ALL patients)
• The patient must have consented to participate and must have signed and dated an IRB-approved consent form that conforms to federal and institutional guidelines.
• Patients must be female.

You may not qualify if:

• Conditions for patient ineligibility (Cohort A)
• FNA alone to diagnose the primary tumor.
• Surgical axillary staging procedure prior to study entry. (Procedures that are permitted include: 1) FNA or core biopsy of an axillary node for any patient, and 2) although not recommended, a pre-neoadjuvant therapy SN biopsy for patients with clinically negative axillary nodes.
• Condition for patient ineligibility (Cohort B)
• Breast reconstruction using tissue expanders or implants at the time of mastectomy.
• Conditions for patient ineligibility (ALL patients)
• Definitive clinical or radiologic evidence of metastatic disease.
• Synchronous bilateral invasive breast cancer.
• History of ipsilateral or contralateral invasive breast cancer regardless of treatment or ipsilateral DCIS treated with RT.
• History of non-breast malignancies within the 5 years prior to study entry. Patients with the following cancers are eligible if diagnosed and treated within the previous 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.
• Prior therapy with anthracyclines, taxanes, trastuzumab, or bevacizumab for any malignancy.
• Treatment including RT, chemotherapy, and/or targeted therapy, administered for the currently diagnosed breast cancer prior to study entry.
• Continued therapy with any hormonal agent such as raloxifene, tamoxifen, or other SERM. (Patients are eligible if these medications are discontinued prior to study entry.)
• Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy, etc. These patients are eligible if this therapy is discontinued prior to study entry. (Women of reproductive potential must agree to use an effective non-hormonal method of contraception during study therapy and for at least 6 months after completion of targeted therapy.)
• Cardiac disease that would preclude the use of the drugs included in the FB-5 treatment regimen. This includes but is not confined to:

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Genentech, Inc.: collaborator
• International Drug Development Institute: collaborator

Study Sites (36)

Clearview Cancer Institute- Huntsville

Huntsville, Alabama, 35801, United States

Location

Kaiser Permanente-San Diego

San Diego, California, 92120, United States

Location

Kaiser Permanente-Vallejo

Vallejo, California, 94589, United States

Location

CCOP, Colorado Cancer Research Program, Inc.

Denver, Colorado, 80224, United States

Location

Baptist Regional Cancer Institute

Jacksonville, Florida, 32207, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

CCOP, Central Illinois

Springfield, Illinois, 62526, United States

Location

CCOP, Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46601, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

NortonHealtcare Inc.

Louisville, Kentucky, 40202, United States

Location

CCOP, Grand Rapids Clnical Oncology Program

Grand Rapids, Michigan, 49503, United States

Location

CCOP, Michigan Cancer Research Consortium

Grosse Pointe Woods, Michigan, 48236, United States

Location

CCOP, Kalamazoo, MI

Kalamazoo, Michigan, 49007, United States

Location

Michigan State University - Breslin Cancer Center

Lansing, Michigan, 48910, United States

Location

CCOP, Metro-Minnesota

Minneapolis, Minnesota, 55416, United States

Location

CCOP, Cancer Research for the Ozarks

Springfield, Missouri, 65804, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

University Hospital and Medical Center - SUNY

Stony Brook, New York, 11794, United States

Location

CCOP, Southeast Cancer Control Consortium

Charlotte, North Carolina, 28203, United States

Location

East Carolina University

Greenville, North Carolina, 27834, United States

Location

Aultman Hospital

Canton, Ohio, 44710, United States

Location

Case Western Reserve/University Hospitals-Ireland Cancer Cntr.

Cleveland, Ohio, 44106, United States

Location

CCOP, Dayton, OH

Dayton, Ohio, 45429, United States

Location

CCOP, Columbia River Oncology

Portland, Oregon, 97225, United States

Location

Kimmel Cancer Center at Jefferson

Philadelphia, Pennsylvania, 19107, United States

Location

Albert Einstein Healthcare Network

Philadelphia, Pennsylvania, 19141-3098, United States

Location

Allegheny General Hospital/Allegheny-Singer Research Institute

Pittsburgh, Pennsylvania, 15212, United States

Location

NSABP Foundation, Inc.

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Mercy Hospital

Scranton, Pennsylvania, 18501, United States

Location

CCOP, Upstate Carolina

Spartanburg, South Carolina, 29303, United States

Location

Joe Arrington Cancer Research & Treatment Center

Lubbock, Texas, 79410, United States

Location

CCOP, Scott and White Memorial Hospital

Temple, Texas, 76508, United States

Location

MBCCOP, Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

CCOP, Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

University of Montreal Hospital Group

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms

Interventions

Epirubicin; Cyclophosphamide; Docetaxel; Trastuzumab; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Director, Department of Site and Study Management
• Organization: NSABP Foundation, Inc.

industrytrials@nsabp.org

1-800-270-3165

Study Officials

• Norman Wolmark, MD

  NSABP Foundation Inc

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2007
• First Posted: April 23, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: May 1, 2014
• Last Updated: October 25, 2021
• Results First Posted: September 26, 2012

Record last verified: 2021-10

Locations

CA (1); US (35)