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Male Breast CancerPhase 2NCT00119262

Bevacizumab and Combination Chemotherapy in Patients With Lymph Node Positive Breast Cancer

A Phase 2 study testing doxorubicin hydrochloride, cyclophosphamide and bevacizumab in people with Male Breast Cancer and Stage II Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial is studying how well giving bevacizumab together with combination chemotherapy works in treating patients who have undergone surgery for breast cancer that has spread to the lymph nodes. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
doxorubicin hydrochloride, cyclophosphamide and bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
226 participants
Where
1 siteUnited States
Study dates
Oct 2005to Sep 2009
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed adenocarcinoma of the breast with involvement of at least one axillary or internal mammary lymph node on routine histologic examination with hematoxylin and eosin staining; NOTE: patients with axillary or internal mammary node involvement only demonstrated by immunohistochemistry are not eligible
  • Patients must have completed definitive breast surgery including total mastectomy and axillary dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy, lumpectomy and axillary dissection, or lumpectomy and sentinel node biopsy; NOTE: axillary dissection is strongly encouraged in patients with lymph node involvement identified on sentinel node biopsy
  • Margins of lumpectomy or mastectomy must be histologically free of invasive breast cancer and ductal carcinoma in situ (DCIS); patients with resection margins positive for lobular carcinoma in situ (LCIS) are eligible
  • (ARM A ONLY) Interval between last surgery for breast cancer (lumpectomy, mastectomy, sentinel node biopsy, axillary dissection or re-excision of lumpectomy margins) and D1 must be > 28 days and =< 84 days
  • ECOG performance status of 0-2
  • Absolute neutrophil count >= 1000/mm^3
Show all 34Show fewer
  • Platelet count >= 100,000/mm^3
  • Total bilirubin =< 1.5 mg/dL
  • AST =< 2 upper limit of normal
  • Serum creatinine =< 1.5 mg/dL
  • Urine protein: creatinine ratio < 1.0
  • PT INR =< 1.5
  • PTT =< 1.5 x normal
  • LVEF >= institutional limits of normal by MUGA or ECHO
  • Prior to registration the investigator must specify if radiation is planned; patients who have undergone a lumpectomy must receive radiation; post-mastectomy radiation is at the investigator's discretion
  • Patients with HER2+ (3+ by IHC or FISH+) breast cancer are not eligible and should be treated with a trastuzumab-based adjuvant therapy
  • Patients with synchronous bilateral breast cancer (diagnosed within one month) are eligible if the higher TMN stage tumor meets the eligibility criteria for this trial
  • Patients must not have clinical evidence of inflammatory disease or fixed axillary nodes (N2) at diagnosis
  • Patients must not have received prior cytotoxic chemotherapy, hormonal therapy or radiation for this breast cancer; prior treatment with an anthracycline, anthracenedione or taxane for any condition is not allowed; NOTE: prior use of tamoxifen for chemoprevention is allowed but must be discontinued at study entry; similarly prior raloxifene use is allowed but must be discontinued at study entry
  • Patients must not have had a major surgical procedure within 4 weeks of entry; NOTE: non-operative biopsy or placement of a vascular access device is not considered a major surgery
  • Patients must not have clinically significant cardiovascular disease including:
  • New York Heart Association (NYHA) grade II or greater congestive heart failure
  • Grade II or greater peripheral vascular disease
  • Uncontrolled hypertension defined as SBP > 160 or DBP > 90
  • Any prior history of cerebrovascular disease including TIA or stroke
  • Patients must not require therapeutic anticoagulation; patients with a history of deep venous thrombosis or pulmonary embolism are not eligible; NOTE: prophylactic use of anticoagulants to maintain patency of a vascular assess device is permitted
  • Patients may not require regular use of aspirin (daily for >= 10 days at doses of > 325 mg/day) or regular therapeutic doses of other nonsteroidal anti-inflammatory agents known to inhibit platelet function; additionally, patients using any of the following drugs known to inhibit platelet function are not eligible: dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and cilostazol (Pletal); NOTE: regular use of Cox-2 inhibitors is permitted; NOTE: low-dose aspirin is permitted
  • Patients must not have a non-healing wound or fracture; patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months are excluded
  • Patients must not have hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies
  • Patients who have experienced myocardial infarction or unstable angina within 12 months are excluded
  • Patients who have had experienced an arterial thrombotic event within 12 months are excluded
  • Patients must not have uncontrolled or clinical significant arrhythmia
  • Women must not be pregnant or breast-feeding due to the potential harmful effects of bevacizumab on the developing fetus; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
  • Women of childbearing potential and sexually active males are required to use an accepted and effective method of contraception while on study and for at least 3-4 months after the last dose of bevacizumab

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Eastern Cooperative Oncology Group

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Phase II Feasibility Trial Incorporating Bevacizumab Into Dose Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel in Patients With Lymph Node Positive Breast Cancer

This phase II trial is studying how well giving bevacizumab together with combination chemotherapy works in treating patients who have undergone surgery for breast cancer that has spread to the lymph nodes. 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 tumor cells by blocking blood flow to the tumor. 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 bevacizumab together with more than one chemotherapy drug (combination chemotherapy), may be a better way to block tumor growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the incidence of clinically apparent cardiac dysfunction in patients with lymph node positive breast cancer treated with bevacizumab and dose dense doxorubicin/cyclophosphamide followed by paclitaxel (ddAC > T).

SECONDARY OBJECTIVES:

  1. To evaluate changes in LVEF during treatment. II. To evaluate non-cardiac toxicity.

OUTLINE: This is a non-randomized, multicenter study. Patients are sequentially assigned to 1 of 2 treatment arms.

Arm A: Patients receive doxorubicin IV, cyclophosphamide IV over 20-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SQ) on days 2-11 or pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients then receive paclitaxel IV over 3 hours and bevacizumab IV over 30-90 minutes on day 1. Patients also receive G-CSF or pegfilgrastim as above. Treatment with paclitaxel, bevacizumab, and G-CSF or pegfilgrastim repeats every 14 days for 4 courses. Patients then receive bevacizumab alone every 14 days for up to 18 courses.

Arm B: Patients receive doxorubicin, cyclophosphamide, and G-CSF or pegfilgrastim as in group I. Patients then receive paclitaxel, bevacizumab, and G-CSF or pegfilgrastim as in group I. Patients then receive bevacizumab alone every 14 days for up to 22 courses.

Treatment in both groups continues in the absence of disease recurrence or unacceptable toxicity.

Patients who require radiotherapy (post-lumpectomy) or who plan radiotherapy at the discretion of the investigator (post-mastectomy) undergo radiotherapy beginning within 6 weeks after the completion of chemotherapy.

Premenopausal patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive disease receive oral tamoxifen once daily for 5 years beginning at the time of radiotherapy or within 6 weeks after the completion of chemotherapy. Postmenopausal patients with ER and/or PR positive disease receive an aromatase inhibitor (e.g., anastrozole, letrozole, or exemestane) or tamoxifen followed by an aromatase inhibitor once daily for up to 10 years.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for up to 3 years from study entry.

ACCRUAL: A total of 226 patients (104 on arm A and 122 on arm B) were accrued for this study.

Medical subject headings
Breast Neoplasms, Male, 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

  • filgrastimBiological

    Also called G-CSF, Neupogen

    Given SC

  • pegfilgrastimBiological

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

    Given SC

  • radiation therapyRadiation

    Also called irradiation, radiotherapy, therapy, radiation

    Undergo radiation therapy

  • tamoxifen citrateDrug

    Also called Nolvadex, TAM, tamoxifen, TMX

    Given orally

  • aromatase inhibition therapyDrug

    Also called inhibition therapy, aromatase

    Receive aromatase inhibition therapy

Study groups in NCT00119262
Study groupRoleWhat they receive
Arm I (combination chemotherapy, 18 courses of bevacizumab)ExperimentalSee detailed description.
Receives: Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: bevacizumab; Drug: paclitaxel; Biological: filgrastim; Biological: pegfilgrastim; Radiation: radiation therapy; Drug: tamoxifen citrate; Drug: aromatase inhibition therapy
Arm II (combination chemotherapy, 22 courses of bevacizumab)Active comparatorSee detailed description.
Receives: Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Biological: bevacizumab; Drug: paclitaxel; Biological: filgrastim; Biological: pegfilgrastim; Radiation: radiation therapy; Drug: tamoxifen citrate; Drug: aromatase inhibition therapy

What is being measured

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

  1. Congestive Heart Failure Rate

    Clinical congestive heart failure includes patients with symptomatic decline in LVEF to at or below the lower limit of normal (LLN), or symptomatic diastolic dysfunction. 223 treated patients were included in the analysis.

    Measured: assessed on day 1 of cycles 5, 9, 17 and 25, and at end of treatment, then every 3 months for <2 years and every 6 months for 2-3 years from study entry

Secondary outcomes (2)

  1. Proportion of Patients With Absolute Decrease in Left Ventricular Ejection Fraction (LVEF) Levels Post Doxorubicin and Cyclophosphamide(AC)

    The endpoint was measured by absolute decrease from baseline in LVEF of >15% or >10% decline from baseline to below the LLN post doxorubicin and cyclophosphamide (AC) Day 1 Cycle 5 (DIC5). 207 patients who were treated and had baseline and DIC5 LVEF values were included in the analysis.

    Measured: assessed on day 1 of cycles 5, 9, 17, 25, and at end of treatment

  2. Proportion of Patients With Absolute Decrease in LVEF Levels Post Bevacizumab

    The endpoint was measured by absolute decrease from baseline in LVEF of >15% or >10% decline from baseline to below the LLN post bevacizumab (the end of treatment). 158 patients who were treated and had baseline and end of treatment LVEF values were included in the analysis.

    Measured: assessed on day 1 of cycles 5, 9, 17, 25, and at end of treatment

Timeline

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

  1. First posted13 Jul 2005 (estimated)
  2. Study startOct 2005
  3. Primary completionAug 2009
  4. Study completionSep 2009

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
226 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00119262
Sponsor's protocol ID
NCI-2012-02977
Other IDs
NCI-2012-02977, U10CA021115, E2104, E2104
Status last verified
Dec 2012
First submitted
12 Jul 2005
Last updated
15 May 2014

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing doxorubicin hydrochloride, cyclophosphamide and bevacizumab in people with Male Breast Cancer and Stage II Breast Cancer, run by National Cancer Institute (NCI) 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 34 inclusion and 0 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: finished, as of the sponsor's last update on 15 May 2014. 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 28 Apr 2011). 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?

Congestive Heart Failure Rate (time frame: assessed on day 1 of cycles 5, 9, 17 and 25, and at end of treatment, then every 3 months for <2 years and every 6 months for 2-3 years from study entry). 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 NCT00119262.

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 15 May 2014.

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