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HER2-negative Breast CancerPhase 2NCT00679029

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

A Phase 2 study testing doxorubicin hydrochloride, cyclophosphamide and bevacizumab in people with HER2-negative Breast Cancer and Stage II Breast Cancer, run by University of Nebraska at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older, women only
What is being tested?
doxorubicin hydrochloride, cyclophosphamide and bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
2 May 2008to 18 Nov 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no greater than 1.5 times the ULN
  • Creatinine less than 1.5 times the ULN
  • Urine protein < 2+ on urinalysis, UPC 1.0 or 24 hour urine < 1 g protein
  • No active serious infections or other condition precluding chemotherapy
  • Able to give informed consent
  • Able to return for treatment and follow-up on the specified days

Who cannot join

  • 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
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  • 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
  • Serious, non-healing wound, ulcer, or bone fracture
  • Proteinuria at screening as demonstrated by either urine protein/creatinine (UPC) ratio >= 1.0 at screening OR urinalysis for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on urinalysis at baseline and undergo a 24 hour urine collection and demonstrate > 1g of protein in 24 hours are ineligible)
  • Known hypersensitivity to any component of Avastin or gemcitabine or other required drugs in the study
  • History of venous or arterial thrombosis
  • Current, ongoing treatment with full-dose warfarin or its equivalent (i.e., unfractionated and/or low molecular weight heparin) for any reason (ASA okay)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

Other trials in United States

About this study

Official title: Adjuvant Doxorubicin, Cyclophosphamide Followed by Avastin Given With Paclitaxel and Gemcitabine for Stage II and III Breast Cancer That Does Not Over-express Human Epidermal Growth Factor Receptor 2 (HER-2)/Neu

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the feasibility of administering two sequential chemotherapy doublets with Avastin in the adjuvant setting.

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

SECONDARY OBJECTIVES:

  1. To determine the effect of Avastin on immunity, especially Vascular endothelial growth factor A (VEGF-A) upregulation of myeloid-derived suppressor cells (MDSC) and suppression of T-Cells.

II. To determine the effect of therapy on numbers of myeloid derived suppressor cells and compare the humoral and cellular response to p53 in breast cancer patients treated with the same chemotherapy.

III. Patients will be followed for freedom from tumor progression and survival.

OUTLINE:

COURSES 1-4: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim subcutaneously (SC) on day 1. Treatment repeats every 2 weeks for 4 courses in the absence of unacceptable toxicity or disease progression.

COURSES 5-7: Patients receive paclitaxel IV and gemcitabine hydrochloride IV on day 1 and pegfilgrastim SC on day 1. Patients also receive bevacizumab IV on day 1 in courses 5-7. Treatment repeats every 2 weeks for 4 courses in the absence of unacceptable toxicity or disease progression.

COURSES 8-16: Patients receive bevacizumab IV alone on day 1. Treatment repeats every 3 weeks for 8 courses in the absence of unacceptable toxicity or disease progression.

After course 8, patients may undergo radiotherapy and hormone therapy, if clinically indicated.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 5 years.

Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • doxorubicin hydrochlorideDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

    Given IV

  • paclitaxelDrug

    Also called Anzatax, Asotax, TAX, Taxol

    Given IV

  • gemcitabine hydrochlorideDrug

    Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

  • pegfilgrastimBiological

    Also called Filgrastim SD-01, GCSF-SD01, Neulasta, SD-01 sustained duration G-CSF

    Given subcutaneously

Study groups in NCT00679029
Study groupRoleWhat they receive
Chemotherapy with BevacizumabExperimentalDoxorubicin 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.
Receives: Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: bevacizumab; Drug: paclitaxel; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis; Biological: pegfilgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: through study completion, an average of 10 months

  2. 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.

    Measured: through study completion, an average of 10 months

Secondary outcomes (2)

  1. Overall Survival as Assessed by the Kaplan and Meier Method

    Overall survival as assessed by the Kaplan and Meier method at 5 years

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

  2. Disease-free Survival

    Disease-free survival as assessed by the Kaplan and Meier method

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2008 (estimated)
  2. Study start2 May 2008
  3. Primary completion18 Nov 2010
  4. Study completion18 Nov 2010

Why it stopped: drug toxicity

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00679029
Sponsor's protocol ID
0412-07-FB
Other IDs
NCI-2009-01693, P30CA036727
Status last verified
Dec 2023
First submitted
15 May 2008
Last updated
11 Dec 2023
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing doxorubicin hydrochloride, cyclophosphamide and bevacizumab in people with HER2-negative Breast Cancer and Stage II Breast Cancer, run by University of Nebraska at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Study Drug-associated Adverse Events Leading to Dose Holds or Reductions (time frame: through study completion, an average of 10 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00679029.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2023.

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