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AzTrials

Breast CancerPhase 3NCT00963729

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

A Phase 3 study testing cyclophosphamide, docetaxel and epirubicin hydrochloride in people with Breast Cancer, run by Imperial College London at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 70 years, women only
Conditions the study is for
Breast Cancer
What is being tested?
cyclophosphamide, docetaxel and epirubicin hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
756 participants
Where
5 sitesin 2 countries
Study dates
Sep 2008to Mar 2011
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

United Kingdom4 sites
  • West Middlesex University Hospital

    Isleworth, England, TW7 6AF

  • Guy's Hospital

    London, England, SE1 9RT

  • St. Mary's Hospital

    London, England, W2 1NY

  • Charing Cross Hospital

    London, England, W6 8RF

Other trials in United Kingdom

South Korea1 site
  • Asan Medical Center - University of Ulsan College of Medicine

    Seoul, 138-736

Other trials in South Korea

About this study

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

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.

Read the 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
Being tested
cyclophosphamide, docetaxel, epirubicin hydrochloride, fluorouracil, letrozole
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
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00963729
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: cyclophosphamide; Drug: docetaxel; Drug: epirubicin hydrochloride; Drug: fluorouracil
Arm IIExperimentalPatients receive oral letrozole daily for 18-23 weeks until day of surgery.
Receives: Drug: letrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility of patient recruitment (pilot)

  2. Feasibility of tissue collection (pilot)

  3. Ultrasound (or mammogram) response rate

Secondary outcomes (13)
  1. Clinical response rate

  2. Radiologic response rate by ultrasound (pilot)

  3. Quality of life

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

  5. Plasma DNA changes in relation to treatment response

  6. Rate of conservation surgery

  7. Degree of pathological response

  8. Ki-67 changes and its relationship to treatment response

  9. Length of time to maximum response within the treatment period

  10. Tolerability of the various treatments

  11. Disease-free survival

  12. Overall survival

  13. MRI response

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2009 (estimated)
  2. Study startSep 2008
  3. Primary completionMar 2010
  4. Study completionMar 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Masking
None (open label)
Enrolment
756 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00963729
Sponsor's protocol ID
ICCRU-NEOcent-C-21-07
Other IDs
CDR0000641383, ICCRU-NEOcent-C-21-07, EU-20936, EUDRACT-2006-003596-12, ISRCTN77234840
Status last verified
Aug 2011
First submitted
20 Aug 2009
Last updated
12 Aug 2013
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cyclophosphamide, docetaxel and epirubicin hydrochloride in people with Breast Cancer, run by Imperial College London at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United Kingdom, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility of patient recruitment (pilot). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2013.

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