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

NCT ID: NCT00963729

Last Updated: 2013-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 756 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2011-03-31

Brief 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.

Detailed 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.

Conditions

Breast Cancer

Keywords

estrogen receptor-positive breast cancer; recurrent breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

epirubicin hydrochloride

Intervention Type: DRUG

Given IV

fluorouracil

Intervention Type: DRUG

Given IV

Arm II

Patients receive oral letrozole daily for 18-23 weeks until day of surgery.

Group Type: EXPERIMENTAL

letrozole

Intervention Type: DRUG

Given orally

Interventions

cyclophosphamide

Given IV

Intervention Type: DRUG

docetaxel

Given IV

Intervention Type: DRUG

epirubicin hydrochloride

Given IV

Intervention Type: DRUG

fluorouracil

Given IV

Intervention Type: DRUG

letrozole

Given orally

Intervention Type: DRUG

Eligibility Criteria

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Imperial College London

OTHER

Sponsor Role: lead

Principal Investigators

R. Charles Coombes, MD, MRCP, FRCP, PhD, FMedSci

Role: STUDY_CHAIR

Charing Cross Hospital

Locations

Asan Medical Center - University of Ulsan College of Medicine

Seoul, , South Korea

West Middlesex University Hospital

Isleworth, England, United Kingdom

Guy's Hospital

London, England, United Kingdom

St. Mary's Hospital

London, England, United Kingdom

Charing Cross Hospital

London, England, United Kingdom

Countries

South Korea; United Kingdom

Other Identifiers

CDR0000641383

Identifier Type: REGISTRY

Identifier Source: secondary_id

ICCRU-NEOcent-C-21-07

Identifier Type: -

Identifier Source: secondary_id

EU-20936

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2006-003596-12

Identifier Type: -

Identifier Source: secondary_id

ISRCTN77234840

Identifier Type: -

Identifier Source: secondary_id

ICCRU-NEOcent-C-21-07

Identifier Type: -

Identifier Source: org_study_id