Chemotherapy or Letrozole Before Surgery in Treating Postmenopausal Women With Breast Cancer That Can Be Removed By Surgery

Breast Cancer Clinical Trial

Official title:

A Neoadjuvant Study of Chemotherapy Versus Endocrine Therapy in Postmenopausal Patients With Primary Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00963729
• Other study ID #: ICCRU-NEOcent-C-21-07
• Secondary ID: CDR0000641383ICC
• Status: Completed
• Phase: Phase 3
• First received: August 20, 2009
• Last updated: August 9, 2013
• Start date: September 2008
• Est. completion date: March 2011

Study information

• Verified date: August 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by reducing the production of estrogen. It is not yet known whether giving more than one drug (combination chemotherapy) or giving letrozole before surgery is more effective in treating women with breast cancer.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy before surgery to see how well it works compared with letrozole given before surgery in treating postmenopausal women with breast cancer that can be removed by surgery.

Description:

OBJECTIVES:

• To compare the efficacy and tolerability of cytotoxic chemotherapy versus aromatase inhibition for the down-staging of strongly ER+ primary breast cancer in postmenopausal women.

• To identify biological predictors of response to these two treatment modalities.

OUTLINE: This is a multicenter pilot, feasibility study followed by a randomized study. In the pilot study, a record of all patients screened and invited to participate in the study is compiled. Reasons for failure to recruit will be recorded. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fluorouracil IV, epirubicin IV, and cyclophosphamide IV on day

1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients who do not achieve at least partial response after 3 courses receive docetaxel IV on day 1 of 3-week courses for an additional 3 courses.

• Arm II: Patients receive oral letrozole daily for 18-23 weeks until day of surgery.

Patients in both arms undergo surgery at week 18-23. Most patients then receive adjuvant therapy.

Quality of life is assessed at baseline, periodically during study treatment, and then during follow up.

Blood is collected pre-treatment, at mid-treatment, and before surgery. Blood is then collected every 6 months for 2 years. Blood samples and preserved tumor samples are used for correlative studies.

After completion of surgery, patients are followed up at least annually for 10 years.

PROJECTED ACCRUAL: A total of 40 patients for the pilot study and 716 patients for the phase III study will be accrued.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 756
• Est. completion date: March 2011
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven primary invasive breast cancer that is thought to be suitable for neoadjuvant treatment

• No cytological proof of malignancy only

• T2 tumor or greater (= 20 mm by ultrasound) or any T stage with nodal disease = 20 mm diameter on ultrasound assessment

• No evidence of distant metastatic disease as disclosed by bone scan, liver, and chest imaging

• Definite indication for neoadjuvant and adjuvant chemotherapy

• Primary tumor amenable to biopsy

• No inoperable disease that is judged very unlikely to be rendered operable by neoadjuvant treatment

• No inflammatory breast cancer

• No bilateral invasive breast cancer

• HER-2 positivity is NOT an exclusion criterion in the feasibility (pilot) study

• Estrogen receptor (ER) positive tumor

• No ER-poor disease as defined locally (e.g., H-score < 100, Allred 3/4/5)

• Allred 6/7/8, H-score H =100 allowed

PATIENT CHARACTERISTICS:

• Postmenopausal, meeting 1 of the following criteria:

• Over 12 months since last menstrual period

• Postmenopausal gonadotrophin levels (luteinizing hormone or follicle-stimulating hormone levels above local criteria)

• Postmenopausal estradiol levels below local criteria

• Prior bilateral oophorectomy

• Menopause induced by gonadotrophin-releasing hormone not allowed

• WHO performance status 0 or 1

• WBC = 3.0 × 10^9/L

• ANC = 1.5 × 10^9/L

• Platelets = 100 × 10^9/L

• Hemoglobin > 9 g/dL

• AST/ALT = 1.5 times upper limit of normal (ULN)

• Serum bilirubin = 1.5 times ULN

• Alkaline phosphatase = 1.5 times ULN

• Serum creatinine = 1.5 times ULN

• No active, uncontrolled infection

• No malignancy within the past 10 years except for basal cell carcinoma or cervical carcinoma in situ

• Treatment for previous malignancy confined to resection alone

• No concomitant medical, psychiatric, or geographic problems that might prevent completion of treatment or follow-up

• No known severe hypersensitivity to aromatase inhibitors

• No contraindication to receiving aromatase inhibitors (clinical evidence or recorded history of osteoporosis)

• No other serious illness or medical condition including any of the following:

• Congestive heart failure or unstable angina pectoris

• Myocardial infarction within the past year

• Uncontrolled hypertension or high-risk uncontrolled arrhythmias

• History of significant neurologic or psychiatric disorders, including psychotic disorders, dementia, or seizures, that would prohibit the understanding and giving of informed consent

• Active peptic ulcer

• Unstable diabetes mellitus

• No definite contraindications for the use of corticosteroids

• No contraindication to receiving combination anthracycline/taxane chemotherapy

• Willing to undergo repeat biopsies

PRIOR CONCURRENT THERAPY:

• No hormone replacement therapy within 4 weeks of starting treatment

• No chronic oral treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (= 20 mg methylprednisolone or equivalent)

• No concurrent warfarin or heparin therapy

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• cyclophosphamide
Given IV
• docetaxel
Given IV
• epirubicin hydrochloride
Given IV
• fluorouracil
Given IV
• letrozole
Given orally

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center - University of Ulsan College of Medicine	Seoul
United Kingdom	West Middlesex University Hospital	Isleworth	England
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	Guy's Hospital	London	England
United Kingdom	St. Mary's Hospital	London	England

Sponsors (1)

Lead Sponsor	Collaborator
Imperial Cancer Clinical Research Unit

Countries where clinical trial is conducted

Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of patient recruitment (pilot)			No
Primary	Feasibility of tissue collection (pilot)			No
Primary	Ultrasound (or mammogram) response rate			No
Secondary	Clinical response rate			No
Secondary	Radiologic response rate by ultrasound (pilot)			No
Secondary	Quality of life			No
Secondary	Pathological complete response rate (pCR) defined as no residual invasive or pre-invasive carcinoma in breast or axilla (pilot)			No
Secondary	Plasma DNA changes in relation to treatment response			No
Secondary	Rate of conservation surgery			No
Secondary	Degree of pathological response			No
Secondary	Ki-67 changes and its relationship to treatment response			No
Secondary	Length of time to maximum response within the treatment period			No
Secondary	Tolerability of the various treatments			Yes
Secondary	Disease-free survival			No
Secondary	Overall survival			No
Secondary	MRI response			No