Chemotherapy & Bevacizumab for Human Epidermal Growth Factor Receptor 2 (HER2)/Neu-Negative Stage II/III Breast Cancer

NCT00679029 | Terminated Phase 2 Results DMC

• 3 other identifiers: 0412-07-FBNCI-2009-01693P30CA036727
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, paclitaxel, and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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 combination chemotherapy together with bevacizumab after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying the side effects and how well giving combination chemotherapy together with bevacizumab works in treating women with HER2/neu-negative stage II or stage III breast cancer

Conditions

HER2-negative Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Study Drug-associated Adverse Events Leading to Dose Holds or Reductions

  This outcome is to measure the feasibility of the of administering two sequential chemotherapy doublets with Avastin in the adjuvant setting in women with stage II and III breast cancer that does not over-express human epidermal growth factor receptor 2 (HER 2)/neu

  through study completion, an average of 10 months

• Count of Participants With Related Serious Adverse Events (SAEs) by NCI Common Toxicity Criteria v3.0

  Assess the safety of Avastin in the adjuvant setting particularly regarding cardiac function, wound healing and toxicity of radiation.

  through study completion, an average of 10 months

Secondary Outcomes (2)

• Overall Survival as Assessed by the Kaplan and Meier Method

  Original time frame: Up to 5 years from date of first treatment; study terminated at 2.5 years

• Disease-free Survival

  From the date of first treatment to the date of disease progression/recurrence, second cancer, or death, whichever came first: Original time frame up to 5 years from date of first treatment; study terminated at 2.5 years

Study Arms (1)

Chemotherapy with Bevacizumab

EXPERIMENTAL

Doxorubicin 60 mg /M2 followed by cyclophosphamide 600 mg/M2 (AC) will be given every 2 weeks for cycles 1-4. Paclitaxel 175 mg/M2 followed by gemcitabine 1500 mg/M2 (TG) will be given every 2 weeks for cycles 5-8. Beginning cycle 5, B1= Avastin 10 mg/kg will be given as a single IV dose following each TG treatment every 2 weeks for cycles 5-7.

Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: bevacizumab; Drug: paclitaxel; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis; Biological: pegfilgrastim

Interventions

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Chemotherapy with Bevacizumab

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Chemotherapy with Bevacizumab

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Chemotherapy with Bevacizumab

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Chemotherapy with Bevacizumab

gemcitabine hydrochloride DRUG

Given IV

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

Chemotherapy with Bevacizumab

laboratory biomarker analysis OTHER

Correlative studies

Chemotherapy with Bevacizumab

pegfilgrastim BIOLOGICAL

Given subcutaneously

Also known as: Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF

Chemotherapy with Bevacizumab

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of invasive breast cancer: By pathologic evaluation, primary tumor must be T1-4N1-3M0 or T3-4N 0M0 that is ER/PR positive or negative and HER-2/neu negative (1+) immunocytochemistry or not amplified by Fluorescence in situ hybridization (FISH)
• OR By pathologic evaluation, primary tumor must be T2N0 that is estrogen receptor (ER), progesterone receptor (PR) and HER-2neu negative
• Women of reproductive potential must be non-pregnant and non-nursing and must agree to employ an effective barrier method of birth control throughout the study and for up to 6 months following treatment
• Women of child-bearing potential, must have a negative pregnancy test within 7 days of initiating study (no childbearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Definitive surgery, lumpectomy and axillary sampling or modified radical mastectomy
• Three weeks since last surgery other than port or right atrial catheter placement
• No significant cardiac disease and a normal left ventricular ejection fraction
• No significant open wounds, uncontrolled hypertension, history of venous or arterial clotting
• Adequate laboratory parameters within 30 days prior to enrollment defined as:
• Absolute neutrophil count greater than or equal to 1,500/mcl
• Platelet count equal to or greater than 150,000/mcl
• Hemoglobin \>11gm/dl
• Alkaline phosphatase equal or less than 1.5 times the upper limit normal (ULN)
• Total bilirubin equal to or less than 1.5 times the ULN

You may not qualify if:

• Prior malignancy; except for adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas, or other cancer from which the patient has been disease free for 5 years
• Prior chemotherapy or radiation therapy
• Breast cancer that over expresses Her-2/neu
• Stage IV or metastatic breast cancer
• Inability to cooperate with treatment protocol
• Any comorbidity or condition which, in the opinion of the investigator, may interfere with the assessments and procedures of this protocol
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 12 months of study enrollment
• Any history of stroke or transient ischemic attack at any time
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Bevacizumab; Paclitaxel; Taxes; Gemcitabine; pegfilgrastim

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Elizabeth Reed
• Organization: University of Nebraska

ereed@unmc.edu

(402) 559-5388

Study Officials

• Elizabeth C Reed, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 15, 2008
• First Posted: May 16, 2008
• Study Start: May 2, 2008
• Primary Completion: November 18, 2010
• Study Completion: November 18, 2010
• Last Updated: December 11, 2023
• Results First Posted: December 12, 2018

Record last verified: 2023-12

Locations

US (1)