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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00963729
First received: August 20, 2009
Last updated: August 9, 2013
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: cyclophosphamide
Drug: docetaxel
Drug: epirubicin hydrochloride
Drug: fluorouracil
Drug: letrozole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Neoadjuvant Study of Chemotherapy Versus Endocrine Therapy in Postmenopausal Patients With Primary Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Feasibility of patient recruitment (pilot) [ Designated as safety issue: No ]
  • Feasibility of tissue collection (pilot) [ Designated as safety issue: No ]
  • Ultrasound (or mammogram) response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical response rate [ Designated as safety issue: No ]
  • Radiologic response rate by ultrasound (pilot) [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]
  • Pathological complete response rate (pCR) defined as no residual invasive or pre-invasive carcinoma in breast or axilla (pilot) [ Designated as safety issue: No ]
  • Plasma DNA changes in relation to treatment response [ Designated as safety issue: No ]
  • Rate of conservation surgery [ Designated as safety issue: No ]
  • Degree of pathological response [ Designated as safety issue: No ]
  • Ki-67 changes and its relationship to treatment response [ Designated as safety issue: No ]
  • Length of time to maximum response within the treatment period [ Designated as safety issue: No ]
  • Tolerability of the various treatments [ Designated as safety issue: Yes ]
  • Disease-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • MRI response [ Designated as safety issue: No ]

Estimated Enrollment: 756
Study Start Date: September 2008
Study Completion Date: March 2011
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: cyclophosphamide
Given IV
Drug: docetaxel
Given IV
Drug: epirubicin hydrochloride
Given IV
Drug: fluorouracil
Given IV
Experimental: Arm II
Patients receive oral letrozole daily for 18-23 weeks until day of surgery.
Drug: letrozole
Given orally

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00963729

Locations
Korea, Republic of
Asan Medical Center - University of Ulsan College of Medicine
Seoul, Korea, Republic of, 138-736
United Kingdom
West Middlesex University Hospital
Isleworth, England, United Kingdom, TW7 6AF
Charing Cross Hospital
London, England, United Kingdom, W6 8RF
Guy's Hospital
London, England, United Kingdom, SE1 9RT
St. Mary's Hospital
London, England, United Kingdom, W2 1NY
Sponsors and Collaborators
Imperial Cancer Clinical Research Unit
Investigators
Study Chair: R. Charles Coombes, MD, MRCP, FRCP, PhD, FMedSci Charing Cross Hospital
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00963729     History of Changes
Other Study ID Numbers: ICCRU-NEOcent-C-21-07, CDR0000641383, ICCRU-NEOcent-C-21-07, EU-20936, EUDRACT-2006-003596-12, ISRCTN77234840
Study First Received: August 20, 2009
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
estrogen receptor-positive breast cancer
recurrent breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Docetaxel
Letrozole
Epirubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites
Antimetabolites, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 20, 2014