Neoadjuvant Complete Hormonal Blockade Followed by Neoadjuvant Chemotherapy for Resectable Hormone Receptor Positive, HER-2/Neu Negative Breast Cancer, A Phase II Study
18 Years
N/A
Female
Estrogen Receptor-positive Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-positive Breast Cancer, Stage I Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
Trial Information
Neoadjuvant Complete Hormonal Blockade Followed by Neoadjuvant Chemotherapy for Resectable Hormone Receptor Positive, HER-2/Neu Negative Breast Cancer, 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 complete hormonal blockade (CHB) for 2
weeks followed by four three-week cycles of Xeloda, Methotrexate and Navelbine with
continuation of complete hormonal blockade.
SECONDARY OBJECTIVES:
I. To assess the clinical response rate in patients with surgically resectable breast cancer
treated with complete hormonal blockade and four three-week cycles of Xeloda, Methotrexate
and Navelbine.
II. To assess the toxicity associated with these regimens. III. To assess the relapse rate,
overall and disease-free survival in patients with operable breast cancer when treated with
neoadjuvant CHB and XMN + CHB followed by adjuvant treatment using XMN or Taxol.
IV. To assess whether the phenotype of breast cancer changes with treatment. V. To assess
whether phenotypic changes in breast tumors predict outcome.
OUTLINE:
NEOADJUVANT CHB: Patients receive exemestane orally (PO) daily for 14 weeks. Premenopausal
patients also receive triptorelin pamoate intramuscularly (IM) once monthly for 4 months
beginning 2 weeks before the initiation of exemestane.
NEOADJUVANT CHEMOTHERAPY: Patients receive capecitabine PO twice daily (BID) on days 1-14
and methotrexate intravenously (IV) and vinorelbine ditartrate IV over 6-10 minutes on days
1, 8, and 15. Treatment repeats every 21 days for 4 courses.
SURGERY: Patients then undergo definitive surgical resection with or without radiation
therapy.
ADJUVANT CHEMOTHERAPY: Patients with microscopic complete response (pCR) or disease that has
been down-staged to =< 1 cm with no positive nodes receive capecitabine PO BID on days 1-14
and methotrexate IV and vinorelbine ditartrate IV over 6-10 minutes on days 1, 8, and 15.
Treatment repeats every 21 days for 4 courses. Patients with down-staged T and 0 or 1
positive node receive paclitaxel IV over 1 hour once weekly for 12 weeks.
ADJUVANT HORMONAL THERAPY: Patients receive hormonal therapy for 5 years.
Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 3 years, every
6 months for 2 years, and then annually thereafter.
Inclusion Criteria:
- Have histologically confirmed, operable ER or PR +, HER2/neu negative,
radiographically measurable breast cancer > 1cm (Operable lesions are T1c - T3 and N0
- N2a; histologic confirmation should be by core needle biopsy only)
- Be chemotherapy naive
- Have an ECOG performance status of =< 2
- Be assessed for menopausal status (For study purposes, postmenopausal is defined as:
a prior documented bilateral oophorectomy, or a history of at least 12 months without
spontaneous menstrual bleeding, or age 60 or older with a prior hysterectomy without
oophorectomy, or Age less than 60 with a prior hysterectomy without oophorectomy [or
in whom the status of the ovaries is unknown], with a documented FSH level
demonstrating confirmatory elevation in the postmenopausal range for the lab)
- All premenopausal patients must have a baseline FSH and LH
- ANC >= 1,500
- Platelet count >= 100,000
- Serum creatinine =< 1.5 x IULN
- Estimated creatinine clearance > 50 ml/min
- Have staging studies and tumor assessment prior to registration
- Bone density exam must be done within the first 3 months of complete hormonal
blockade
- Have a negative pregnancy test within seven days prior to registration if of
childbearing potential
- 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; women of childbearing potential with either a positive or no
pregnancy test at baseline are excluded (Women of childbearing potential who are not
using a reliable and appropriate contraceptive method are excluded; patients must
agree to continue contraception for 30 days from the last study drug administration)
- Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity
to 5-fluorouracil
- Previous enrollment in an investigational drug study within the last 4 weeks
- Evidence of distant metastatic disease
- Prior chemotherapy or hormonal therapy for breast cancer
- Prior malignancy other than adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, other stage I or II cancer from which the patient
has been disease free for at least 5 years
- 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
- Any other life-threatening illness (e.g. serious, uncontrolled concurrent infection
or clinically significant cardiac disease - congestive heart failure, symptomatic
coronary artery disease, cardiac arrhythmia not well controlled with medication or
myocardial infarction
- Major surgery within four 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 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:
Clinical response
Outcome Description:
Defined as a > 50% decrease in sum of the products of the perpendicular diameters of bidimensionally measurable disease.
Outcome Time Frame:
1 month
Safety Issue:
No
Principal Investigator
Hannah Linden
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Authority:
United States: Institutional Review Board
Study ID:
6277
NCT ID:
NCT00194792
Start Date:
August 2005
Completion Date:
July 2011
Related Keywords:
- Estrogen Receptor-positive Breast Cancer
- HER2-negative Breast Cancer
- Progesterone Receptor-positive Breast Cancer
- Stage I Breast Cancer
- Stage II Breast Cancer
- Stage IIIA Breast Cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington 98109 |
