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Estrogen Receptor-negative Breast CancerPhase 2NCT00194779

Combination Chemotherapy and Filgrastim Before Surgery in Treating Patients With HER2-Positive Breast Cancer That Can Be Removed By Surgery

A Phase 2 study testing doxorubicin hydrochloride, cyclophosphamide and paclitaxel in people with Estrogen Receptor-negative Breast Cancer and Estrogen Receptor-positive Breast Cancer, run by University of Washington 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 studies how well giving combination chemotherapy and filgrastim together before surgery works in treating patients with human epidermal growth receptor 2 (HER2)-positive breast cancer that can be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
doxorubicin hydrochloride, cyclophosphamide and paclitaxel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
Oct 2003to Jun 2011
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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Have known tumor HER-2/neu expression; if determination is "intermediate" by immunohistochemistry, fluorescent in situ hybridization (FISH) must be performed; protocol therapy is determined by HER-2/neu result
  • Have histologically confirmed, operable breast cancer that is either:
  • Hormone receptor (estrogen receptor [ER] or progesterone receptor [PR]) positive and HER2/neu positive or
  • ER/PR negative
  • Have radiographically measurable breast cancer > 1cm (Operable lesions are T1c-T3 and N0-N2a; histologic confirmation should be by core needle biopsy only)
  • Be chemotherapy naïve
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  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Absolute neutrophil count (ANC) >= 1,500
  • Platelet count >= 100,000
  • Serum creatinine =< 1.5 x international upper limit of normal (IULN)
  • Bilirubin < 2.0
  • Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvate transaminase (SGPT) =< 2 x IULN
  • Alkaline phosphatase =< 2 x IULN
  • Have staging studies and tumor assessment prior to registration; staging studies include physical exam with bidimensional tumor measurements and mammography, ultrasound, or magnetic resonance imaging (MRI) to assess tumor volume; sentinel lymph node dissection or axillary needle biopsy must be completed prior to enrollment; MRI and positron emission tomography (PET) (fluorodeoxyglucose [FDG], methoxyisobutylisonitrile [MIBI] and fluoroestradiol [FES]) imaging will be done before enrollment if clinically indicated to assess tumor volume or may be done within the first month of study participation on another institutional protocol
  • Patients with clinically apparent cardiac disease, or history of same, are not eligible; patients who are >= 60 years of age or who have a history of hypertension must have an echocardiogram or multi gated acquisition scan (MUGA) prior to enrollment; patients with breast cancer that is HER-2/neu positive who will receive herceptin (trastuzumab) must have an echocardiogram or MUGA scan; the left ventricular ejection fraction (LVEF) must be within the institutional normal range; if LVEF is > 75%, the investigator should consider having the LVEF reviewed or repeating the MUGA prior to registration
  • Women of childbearing potential must have a negative pregnancy test within seven days prior to registration
  • Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study specific screening procedures

Who cannot join

  • Primary tumor =< 1 cm, not measurable; inflammatory disease
  • Pregnant or lactating; woman of childbearing potential with either a positive or no pregnancy test at baseline are excluded; postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential; patients must agree to continue contraception for 30 days from the date of the last study drug administration; woman of childbearing potential not using a reliable and appropriate contraceptive method are excluded
  • Evidence of distant metastatic disease
  • Prior chemotherapy or hormonal therapy for breast cancer
  • Except for the following no other malignancy is allowed: synchronous ipsilateral breast cancer of the same subtype (ER/PR, HER-2/neu), adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other stage I or II cancer from which the patient has been disease free for at least 5 years
  • Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil
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  • Previous enrollment in an investigational drug study within the past four weeks
  • History of uncontrolled seizures, central nervous system disorders, or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance with oral drug intake
  • Patients with cardiac disease that would preclude the use of Adriamycin, Taxol or Herceptin are not eligible
  • Active cardiac disease:
  • Angina pectoris that requires the use of antianginal medication
  • Cardiac arrhythmia requiring medication
  • Severe conduction abnormality
  • Clinically significant valvular disease
  • Cardiomegaly on chest x-ray
  • Ventricular hypertrophy on electrocardiogram (EKG)
  • Uncontrolled hypertension, (diastolic greater than 100 mm/Hg or systolic > 200 mm/hg)
  • Current use of digitalis or beta blockers for congestive heart failure (CHF)
  • Clinically significant pericardial effusion
  • History of cardiac disease:
  • Myocardial infarction documented as a clinical diagnosis or by EKG or any other test
  • Documented congestive heart failure
  • Documented cardiomyopathy
  • Documented arrhythmia or cardiac valvular disease that requires medication or is medically significant
  • Major surgery within 4 weeks of the start of study treatment without complete recovery
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
  • Known, existing uncontrolled coagulopathy
  • Unwillingness to give written informed consent
  • Unwillingness to participate or inability to comply with the protocol for the duration of the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Study of Weekly Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF Followed by Weekly Paclitaxel as Neoadjuvant Therapy for Resectable, Hormone Receptor Negative or Hormone Receptor Positive, HER-2/Neu Positive Breast Cancer Followed by a Novel Regimen of Capecitabine, Methotrexate and Vinorelbine for Patients Who Do Not Have Either a Macroscopic or Microscopic Pathologic Complete Response, a Phase II Study

This phase II trial studies how well giving combination chemotherapy and filgrastim together before surgery works in treating patients with human epidermal growth receptor 2 (HER2)-positive breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Colony-stimulating factors, such as filgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving doxorubicin hydrochloride, cyclophosphamide, and filgrastim together followed by paclitaxel before surgery may be an effective treatment for breast cancer

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the pathologic response rate in patients with operable breast cancer treated with a two part, neoadjuvant regimen consisting of weekly doxorubicin (doxorubicin hydrochloride) and daily oral cyclophosphamide given with G-CSF (filgrastim) support for 12 weeks followed weekly paclitaxel for 12 weeks.

SECONDARY OBJECTIVES:

  1. To assess the clinical response rate in patients with surgically resectable breast cancer treated with weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 12 weeks.

II. To assess the clinical response rate in patients with surgically resectable breast cancer treated with weekly paclitaxel for 12 weeks.

III. To assess the relapse rate, overall and disease-free survival in patients with operable breast cancer treated with neoadjuvant chemotherapy consisting of weekly doxorubicin and daily oral cyclophosphamide given with G-CSF support for 12 weeks followed weekly paclitaxel for 12 weeks and adjuvant chemotherapy with Xeloda (capecitabine), Methotrexate and Navelbine (vinorelbine tartrate) (XMN).

IV. To assess the toxicity associated with these regimens. V. To assess whether the phenotype of breast cancer changes with treatment. VI. To assess whether phenotypic changes in breast tumors predict outcome.

OUTLINE:

PART I: Patients receive doxorubicin hydrochloride intravenously (IV) on day 1 of each week, cyclophosphamide orally (PO) once daily (QD), and filgrastim subcutaneously (SC) QD on days 2-7 of each week. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity.

PART II: Patients* receive paclitaxel IV over 1 hour on day 1 of each week. Treatment continues for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo definitive surgical resection by partial mastectomy (lumpectomy) or mastectomy after completion of neoadjuvant chemotherapy.

PART III: Patients** unable to achieve complete pathologic response (pCR) or disease that has been down-staged to =< 1 cm with no positive nodes following surgery receive capecitabine PO twice daily (BID) on days 1-14, methotrexate IV on days 1, 8 and 15, and vinorelbine tartrate IV over 6-10 minutes on days 1, 8, and 15. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients with HER2/neu-positive disease also receive trastuzumab IV over 30-90 minutes once weekly or every 3 weeks for 1 year beginning in Part II.

NOTE: **Patients with hormone receptor-positive disease also receive tamoxifen PO QD for 5 years (premenopausal) OR letozole PO QD or tamoxifen PO QD for 5 years (postmenopausal) beginning in Part III.

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

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 PO

  • paclitaxelDrug

    Also called Anzatax, Asotax, TAX, Taxol

    Given IV

  • filgrastimBiological

    Also called G-CSF, Neupogen

    Given SC

  • capecitabineDrug

    Also called CAPE, Ro 09-1978/000, Xeloda

    Given PO

  • methotrexateDrug

    Also called amethopterin, Folex, methylaminopterin, Mexate

    Given IV

  • vinorelbine tartrateDrug

    Also called Eunades, navelbine ditartrate, NVB, VNB

    Given IV

  • needle biopsyProcedure or surgery

    Also called aspiration biopsy, puncture biopsy

    Correlative studies

  • therapeutic conventional surgeryProcedure or surgery

    Undergo definitive breast surgery

  • immunohistochemistry staining methodOther

    Also called immunohistochemistry

    Correlative studies

  • trastuzumabBiological

    Also called anti-c-erB-2, Herceptin, MOAB HER2

    Given IV

  • tamoxifen citrateDrug

    Also called Nolvadex, TAM, tamoxifen, TMX

    Given PO

  • letrozoleDrug

    Also called CGS 20267, Femara, LTZ

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00194779
Study groupRoleWhat they receive
Treatment (neoadjuvant therapy, adjuvant therapy)ExperimentalSee Detailed Description.
Receives: Drug: doxorubicin hydrochloride; Drug: cyclophosphamide; Drug: paclitaxel; Biological: filgrastim; Drug: capecitabine; Drug: methotrexate; Drug: vinorelbine tartrate; Procedure: needle biopsy; Procedure: therapeutic conventional surgery; Other: immunohistochemistry staining method; Biological: trastuzumab; Drug: tamoxifen citrate; Drug: letrozole; Other: laboratory biomarker analysis

What is being measured

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

  1. Combined Rate of Microscopic pCR and Macroscopic Pathologic Complete Response (mCR)

    Microscopic pCR: No evidence of microscopic invasive tumor at the primary site or in the regional lymph nodes at the time of definitive surgical resection. mCR: The examining pathologist cannot identify gross residual tumor mass in the surgical specimen. This differs from a pCR where the specimen must also be negative for invasive tumor by microscopy. For this study, we are using a definition of mCR that will make the trial more translatable to other institutions. For this study, mCR will be defined as no focus of invasive cancer >= 1 cm.

    Count of participants with either a pCR or mCR.

    Measured: Up to 16 weeks

Secondary outcomes (8)

  1. Number and Percent of Patients Reporting Grade 2, 3, 4, or Fatal Toxicities of These Regimens, Need for Dose Reduction, or Treatment Interruption or Discontinuation

    Measured: From the initiation of study treatments to 30 days after the end of neoadjuvant treatment or adjuvant treatment if received

  2. Correlation of Molecular Markers With Response

    Measured: After completion of neoadjuvant therapy

  3. Relapse Rate in Patients With Operable Breast Cancer Treated With Neoadjuvant Chemotherapy for 12 Weeks Followed by Weekly Paclitaxel for 12 Weeks and Adjuvant Chemotherapy

    Count of patients that relapsed.

    Measured: Up to 8 years

  4. Time to Progression

    Median time to progression free survival.

    Measured: Up to 5 years

  5. OS in Patients With Operable Breast Cancer Treated With Neoadjuvant Chemotherapy for 12 Weeks Followed Weekly Paclitaxel for 12 Weeks and Adjuvant Chemotherapy With XMN

    Kaplan-Meier estimate of overall survival, assessed at 1, 2, and 5 years.

    Measured: 1, 2, and 5 years

  6. Disease-free Survival

    Kaplan-Meier estimate of disease-free survival, assessed at 1, 2, and 5 years.

    Measured: 1, 2, and 5 years

  7. Clinical Response to Neoadjuvant Therapy

    Measured: Up to 12 weeks

  8. Clinical Response to Paclitaxel

    Measured: Up to 24 weeks

Timeline

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

  1. First posted19 Sep 2005 (estimated)
  2. Study startOct 2003
  3. Primary completionJun 2010
  4. Study completionJun 2011

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
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00194779
Sponsor's protocol ID
6278
Other IDs
NCI-2011-00934
Status last verified
Feb 2018
First submitted
13 Sep 2005
Last updated
12 Mar 2018
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing doxorubicin hydrochloride, cyclophosphamide and paclitaxel in people with Estrogen Receptor-negative Breast Cancer and Estrogen Receptor-positive Breast Cancer, run by University of Washington 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 17 inclusion and 29 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 12 Mar 2018. 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 Mar 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?

Combined Rate of Microscopic pCR and Macroscopic Pathologic Complete Response (mCR) (time frame: Up to 16 weeks). 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 NCT00194779.

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 12 Mar 2018.

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