Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Women With Hormone Receptor-Positive Breast Cancer That Can be Removed by Surgery
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Cancer
Intervention: capecitabine (Drug); exemestane (Drug); methotrexate (Drug); paclitaxel (Drug); triptorelin (Drug); vinorelbine ditartrate (Drug); adjuvant therapy (Procedure); conventional surgery (Procedure); neoadjuvant therapy (Procedure)
Phase: Phase 2
Sponsored by: Fred Hutchinson Cancer Research Center
Official(s) and/or principal investigator(s):
Hannah M. Linden, MD, Principal Investigator, Affiliation: Seattle Cancer Care Alliance
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using
exemestane and triptorelin may fight breast cancer by lowering the amount of estrogen the
body makes. Drugs used in chemotherapy, such as capecitabine, methotrexate, vinorelbine, 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 hormone therapy together with combination
chemotherapy before surgery may make the tumor smaller and reduce the amount of normal
tissue that needs to be removed. Giving these treatments after surgery may kill any tumor
cells that remain after surgery.
PURPOSE: This phase II trial is studying how well giving hormone therapy together with
combination chemotherapy before and after surgery works in treating women with hormone
receptor-positive breast cancer that can be removed by surgery.
Official title: Neoadjuvant Complete Hormonal Blockade Followed by Neoadjuvant Chemotherapy for Resectable, Hormone Receptor Positive, HER-2/Neu Negative Breast Cancer, A Phase II Study
Study design: Allocation: Non-Randomized, Primary Purpose: Treatment
Microscopic pathologic complete response
Macroscopic pathologic complete response
Relapse rate, disease-free survival, and overall survival
Quantification of all grade 2, 3, 4 or fatal toxicity
Need for dose reduction
Treatment interruption, or treatment discontinuation
Secondary outcome: Correlation of molecular markers with response, time to progression, and survival
- To assess the pathologic response rate in women with hormone receptor-positive
resectable breast cancer treated with neoadjuvant therapy comprising complete hormonal
blockade and capecitabine, methotrexate, and vinorelbine followed by surgery and
adjuvant therapy comprising paclitaxel or capecitabine, methotrexate, and vinorelbine.
- To assess the clinical response rate in patients treated with this regimen.
- To assess the toxicity of this regimen in these patients.
- To assess the relapse rate, overall survival, and disease-free survival of patients
treated with this regimen.
- To assess whether the phenotype of breast cancer changes with treatment.
- To assess whether phenotypic changes in breast tumors predict outcome.
OUTLINE: This is a multicenter study.
- Neoadjuvant complete hormonal blockade (CHB): Patients receive oral exemestane once
daily for 14 weeks. Premenopausal patients also receive triptorelin intramuscularly
once a month for 4 months beginning 2 weeks before the initiation of exemestane.
- Neoadjuvant chemotherapy: Beginning 2 weeks after the initiation of CHB, patients also
receive XMN chemotherapy comprising oral capecitabine twice daily on days 1-14 and
methotrexate IV and vinorelbine IV on days 1, 8, and 15. Treatment with XMN
chemotherapy repeats every 21 days for 4 courses.
- Surgery: After completion of neoadjuvant therapy, patients undergo definitive breast
surgery by lumpectomy or mastectomy, with or without radiation therapy as determined by
the treating physician.
Patients with complete pathologic response or disease that has been down-staged to ≤ 1 cm
with no positive lymph nodes proceed to adjuvant chemotherapy with XMN. Patients with
down-staged T with ≤ 1 positive lymph node proceed to adjuvant chemotherapy with paclitaxel.
Patients without down-staged T, > 1 positive lymph node are removed from the study.
- Adjuvant chemotherapy: Patients receive XMN chemotherapy comprising oral capecitabine
twice daily on days 1-14 and methotrexate IV and vinorelbine IV on days 1, 8, and 15.
Treatment repeats every 21 days for 4 courses. Alternatively, patients receive
paclitaxel IV once weekly for 12 weeks.
- Adjuvant hormonal therapy: After completion of adjuvant chemotherapy, patients receive
adjuvant hormonal therapy for 5 years. The type of hormonal therapy will be at
discretion of the treating physician.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then
Minimum age: 18 Years.
Maximum age: N/A.
- Histologically confirmed* breast cancer
- Operable disease (stage T1c-T3 and N0- N2a disease) NOTE: *By core needle biopsy
- Must have undergone staging studies and tumor assessment, including sentinel lymph
node dissection or axillary node biopsy
- Radiographically measurable disease > 1 cm
- HER2/neu negative disease
- No inflammatory disease
- No distant metastatic disease
- Hormone receptor status:
- Estrogen receptor- or progesterone receptor-positive disease
- Premenopausal or postmenopausal
- Postmenopausal is defined by 1 of the following:
- Prior documented bilateral oophorectomy
- No spontaneous menstrual bleeding for ≥ 12 months
- Age 60 years or older and underwent a prior hysterectomy without
- Under 60 years of age and underwent a prior hysterectomy without
oophorectomy (or in whom the status of the ovaries is unknown), with a
documented follicle-stimulating hormone (FSH) level demonstrating
confirmatory elevation in the postmenopausal range
- All premenopausal patients must have baseline FSH and luteinizing hormone levels
- ECOG performance status 0-2
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin normal
- Serum creatinine ≤ 1. 5 times upper limit of normal (ULN)
- Creatinine clearance > 50 mL/min
- Bilirubin ≤ 1. 5 times ULN
- SGOT/SGPT ≤ 1. 5 times ULN
- Alkaline phosphatase ≤ 2. 5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 30 days after
completion of study treatment
- No prior unanticipated severe reaction to fluoropyrimidine therapy or known
sensitivity to fluorouracil
- No prior malignancy except 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 ≥ 5 years
- No history of uncontrolled seizures or central nervous system disorders
- No clinically significant psychiatric disability that would preclude study
participation or informed consent
- No other life-threatening illness (e. g., serious, uncontrolled infection or
clinically significant cardiac disease, including congestive heart failure,
symptomatic coronary artery disease, cardiac arrhythmia that is not well controlled
with medication, or myocardial infarction)
- No lack of physical integrity of the upper gastrointestinal tract
- No malabsorption syndrome
- No known, existing uncontrolled coagulopathy
PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior enrollment in an investigational drug study
- More than 4 weeks since prior major surgery and recovered
- No prior chemotherapy or hormonal therapy for breast cancer
- No concurrent sorivudine or brivudine (during treatment with capecitabine)
Locations and Contacts
Seattle Cancer Care Alliance, Seattle, Washington 98109-1023, United States; Recruiting
Clinical Trials Office - Seattle Cancer Care Alliance, Phone: 800-804-8824
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: October 2003
Last updated: November 20, 2009