Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Women With Hormone Receptor-Positive Breast Cancer That Can be Removed by Surgery

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

Status: Recruiting

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

Primary outcome:

Clinical response

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

Detailed description: OBJECTIVES:

Primary

- 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.

Secondary

- 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 annually thereafter.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed* breast cancer

- Operable disease (stage T1c-T3 and N0- N2a disease) NOTE: *By core needle biopsy

only

- 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

PATIENT CHARACTERISTICS:

- Female

- 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

oophorectomy

- 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)

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