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

NCT00963729 | Completed Phase 3

• 5 other identifiers: ICCRU-NEOcent-C-21-07CDR0000641383EU-20936EUDRACT-2006-003596-12ISRCTN77234840
• Study Type: interventional
• Target: 756
• Locations: 2 countries
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (3)

• Feasibility of patient recruitment (pilot)

• Feasibility of tissue collection (pilot)

• Ultrasound (or mammogram) response rate

Secondary Outcomes (13)

• Clinical response rate

• Radiologic response rate by ultrasound (pilot)

• Quality of life

• Pathological complete response rate (pCR) defined as no residual invasive or pre-invasive carcinoma in breast or axilla (pilot)

• Plasma DNA changes in relation to treatment response

Study Arms (2)

Arm I

EXPERIMENTAL

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.

Drug: cyclophosphamide; Drug: docetaxel; Drug: epirubicin hydrochloride; Drug: fluorouracil

Arm II

EXPERIMENTAL

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

Drug: letrozole

Interventions

cyclophosphamide DRUG

Given IV

Arm I

docetaxel DRUG

Given IV

Arm I

epirubicin hydrochloride DRUG

Given IV

Arm I

fluorouracil DRUG

Given IV

Arm I

letrozole DRUG

Given orally

Arm II

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (5)

Asan Medical Center - University of Ulsan College of Medicine

Seoul, 138-736, South Korea

Location

West Middlesex University Hospital

Isleworth, England, TW7 6AF, United Kingdom

Location

Guy's Hospital

London, England, SE1 9RT, United Kingdom

Location

St. Mary's Hospital

London, England, W2 1NY, United Kingdom

Location

Charing Cross Hospital

London, England, W6 8RF, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide; Docetaxel; Epirubicin; Fluorouracil; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Diterpenes; Terpenes; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitriles; Triazoles; Azoles

Study Officials

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

  Charing Cross Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 20, 2009
• First Posted: August 21, 2009
• Study Start: September 1, 2008
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2011
• Last Updated: August 12, 2013

Record last verified: 2011-08

Locations

GB (4); KR (1)