Know Cancer

or
forgot password

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


Phase 2
18 Years
N/A
Not Enrolling
Female
Estrogen Receptor-negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, HER2-positive Breast Cancer, Progesterone Receptor-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer

Thank you

Trial Information

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


PRIMARY OBJECTIVES:

I. 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:

I. 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.


Inclusion Criteria:



- 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

- 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

Exclusion Criteria:

- 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

- 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Combined rate of microscopic pCR and macroscopic pathologic complete response (mCR)

Outcome Description:

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.

Outcome Time Frame:

At the end of part II, before surgical resection

Safety Issue:

No

Principal Investigator

Georgiana Ellis

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

6278

NCT ID:

NCT00194779

Start Date:

October 2003

Completion Date:

Related Keywords:

  • Estrogen Receptor-negative Breast Cancer
  • Estrogen Receptor-positive Breast Cancer
  • HER2-positive Breast Cancer
  • Progesterone Receptor-negative Breast Cancer
  • Progesterone Receptor-positive Breast Cancer
  • Stage IA Breast Cancer
  • Stage IB Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Breast Neoplasms

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109