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.
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
- Type of treatment
- Pill or oral medicine, Injection or infusion
- 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
South Korea1 site
Asan Medical Center - University of Ulsan College of Medicine
Seoul, 138-736
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.
cyclophosphamideDrug
Given IV
docetaxelDrug
Given IV
epirubicin hydrochlorideDrug
Given IV
fluorouracilDrug
Given IV
letrozoleDrug
Given orally
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Rate of conservation surgery
Degree of pathological response
Ki-67 changes and its relationship to treatment response
Length of time to maximum response within the treatment period
Tolerability of the various treatments
Disease-free survival
Overall survival
MRI response
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2009 (estimated)
- Study startSep 2008
- Primary completionMar 2010
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Investigators
- R. Charles Coombes, MD, MRCP, FRCP, PhD, FMedSci, Study chair, Charing Cross Hospital
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
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Neoadjuvant Study of Chemotherapy Versus Endocrine Therapy in Postmenopausal Patients With Primary Breast Cancer
- ClinicalTrials.gov ID
- NCT00963729
- Acronym / sponsor ID
- ICCRU-NEOcent-C-21-07
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 756 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 21 Aug 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: cyclophosphamide, Drug: docetaxel, Drug: epirubicin hydrochloride, Drug: fluorouracilPatients 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. |
| Arm II | Experimental | Drug: letrozolePatients receive oral letrozole daily for 18-23 weeks until day of surgery. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclophosphamideGiven IV | Drug | Arm I |
| docetaxelGiven IV | Drug | Arm I |
| epirubicin hydrochlorideGiven IV | Drug | Arm I |
| fluorouracilGiven IV | Drug | Arm I |
| letrozoleGiven orally | Drug | Arm II |
Primary outcome
Feasibility of patient recruitment (pilot)
Feasibility of tissue collection (pilot)
Ultrasound (or mammogram) response rate
13 secondary outcomes
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
Rate of conservation surgery
Degree of pathological response
Ki-67 changes and its relationship to treatment response
Length of time to maximum response within the treatment period
Tolerability of the various treatments
Disease-free survival
Overall survival
MRI response
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
R. Charles Coombes, MD, MRCP, FRCP, PhD, FMedSci study chair
Charing Cross Hospital
5 sites in 2 countries: see every site and its status.
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.