Breast CancerPhase 3NCT00003577
Combination Chemotherapy With or Without Epirubicin in Treating Women With Stage I or Stage II Breast Cancer
A Phase 3 study testing CMF regimen, cyclophosphamide and epirubicin hydrochloride in people with Breast Cancer, run by University Hospital Birmingham at 1 site in United Kingdom.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether combination chemotherapy plus epirubicin is more effective than combination chemotherapy alone for stage I or stage… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- CMF regimen, cyclophosphamide and epirubicin hydrochloride
- Type of treatment
- Surgery or procedure
- How many people
- 2,000 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 1996to Sep 2008
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Histological confirmation of invasive, early stage breast cancer
- Prior complete excision of tumor required (wide local excision or mastectomy)
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age:
- Not specified
Sex:
- Female
Menopausal status:
- Pre-, peri-, or post-menopausal
Performance status:
- Not specified
Hematopoietic:
- Adequate bone marrow function
Hepatic:
- Adequate hepatic function
Renal:
- Adequate renal function
Other:
- No prior cancer except for basal cell carcinoma or carcinoma in situ
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- Concurrent hormone therapy allowed
Radiotherapy:
- No prior radiotherapy
- Concurrent radiotherapy allowed
Surgery:
- See Disease Characteristics
- No more than 6 weeks since prior surgery to the breast
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Cambridge
Cambridge, England, CB2 2QQ
About this study
Official title: National Breast Cancer Study of Epirubicin + CMF v Classical CMF Adjuvant Therapy
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether combination chemotherapy plus epirubicin is more effective than combination chemotherapy alone for stage I or stage II breast cancer.
PURPOSE: This randomized phase III trial is studying combination chemotherapy alone to see how well it works compared to combination chemotherapy and epirubicin in treating women with stage I or stage II breast cancer who have undergone surgery to remove the tumor.
Read the detailed description
OBJECTIVES:
- Compare disease-free and overall survival of women with early stage breast cancer treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil with or without epirubicin.
- Compare the quality of life in a subgroup of these patients treated with these regimens.
OUTLINE: This is a randomized study. Patients are stratified according to radiotherapy timing (concurrent versus sequential), nodal status (negative versus 1-3 versus at least 4), age (50 and under versus over 50), grade, and tumor size. Patients are randomized to one of two treatment arms.
- Arm I: Patients receive oral cyclophosphamide on days 1-14 and methotrexate IV and fluorouracil IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses.
- Arm II: Patients receive epirubicin IV on day 1 every 3 weeks for 4 courses followed by cyclophosphamide, methotrexate, and fluorouracil, as in arm I, for 4 courses.
Some patients may receive radiotherapy during or after chemotherapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed in a subset of patients (N=500) before chemotherapy starts, at 3 months of treatment, at the end of chemotherapy, and at 6, 12, and 18 months after treatment.
Patients are followed annually for 10 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: Approximately 2,000 patients will be accrued for this study within 4 years.
- Conditions
- Breast Cancer
- Being tested
- CMF regimen, cyclophosphamide, epirubicin hydrochloride, fluorouracil, methotrexate
- Keywords
- stage I breast cancer, stage II 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.
CMF regimenDrug
cyclophosphamideDrug
epirubicin hydrochlorideDrug
fluorouracilDrug
methotrexateDrug
adjuvant therapyProcedure or surgery
radiation therapyRadiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startMar 1996
- Study completionSep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham
- Sponsor type
- University, hospital or other
- Investigators
- Helena Earl, MBBS, PhD, FRCP, Study chair, Cambridge University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003577
- Sponsor's protocol ID
- CDR0000066644
- Other IDs
- CRC-TU-NEAT, EU-98041
- Status last verified
- Feb 2001
- First submitted
- 1 Nov 1999
- Last updated
- 19 Dec 2013
- Results posted
- No
Publications
Earl H, Hiller L, Dunn JA, et al.: The National Epirubicin Adjuvant Trial (NEAT) and Scottish Cancer Trials Breast Group (SCTBG) br9601 randomized phase III adjuvant early breast cancer trials: the updated definitive joint analysis. [Abstract] J Clin Oncol 25 (Suppl 18): A-534, 11s, 2007.
Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. doi: 10.1056/NEJMoa052084.
PubMed 17079759Poole CJ, Earl HM, Dunn JA, et al.: NEAT (National Epirubicin Adjuvant Trial) and SCTBG BR9601 (Scottish Cancer Trials Breast Group) phase III adjuvant breast trials show a significant relapse-free and overall survival advantage for sequential ECMF. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-13, 4, 2003.
Earl HM, Hiller L, Dunn JA, Bathers S, Harvey P, Stanley A, Grieve RJ, Agrawal RK, Fernando IN, Brunt AM, McAdam K, O'Reilly S, Rea DW, Spooner D, Poole CJ; NEAT Investigators. NEAT: National Epirubicin Adjuvant Trial--toxicity, delivered dose intensity and quality of life. Br J Cancer. 2008 Oct 21;99(8):1226-31. doi: 10.1038/sj.bjc.6604674. Epub 2008 Sep 16.
PubMed 18797468Ali HR, Glont SE, Blows FM, Provenzano E, Dawson SJ, Liu B, Hiller L, Dunn J, Poole CJ, Bowden S, Earl HM, Pharoah PD, Caldas C. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol. 2015 Jul;26(7):1488-93. doi: 10.1093/annonc/mdv192. Epub 2015 Apr 20.
PubMed 25897014Ali HR, Provenzano E, Dawson SJ, Blows FM, Liu B, Shah M, Earl HM, Poole CJ, Hiller L, Dunn JA, Bowden SJ, Twelves C, Bartlett JM, Mahmoud SM, Rakha E, Ellis IO, Liu S, Gao D, Nielsen TO, Pharoah PD, Caldas C. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol. 2014 Aug;25(8):1536-43. doi: 10.1093/annonc/mdu191. Epub 2014 Jun 9.
PubMed 24915873
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- National Breast Cancer Study of Epirubicin + CMF v Classical CMF Adjuvant Therapy
- ClinicalTrials.gov ID
- NCT00003577
- Acronym / sponsor ID
- CDR0000066644
- Conditions
- Breast Cancer
- Keywords
- stage I breast cancer, stage II breast cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- University Hospital BirminghamUniversity, hospital or other
- Study start
- Mar 1996
- Study completion
- Sep 2008 (actual)
- First posted
- 27 Jan 2003 (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 use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether combination chemotherapy plus epirubicin is more effective than combination chemotherapy alone for stage I or stage II breast cancer.
PURPOSE: This randomized phase III trial is studying combination chemotherapy alone to see how well it works compared to combination chemotherapy and epirubicin in treating women with stage I or stage II breast cancer who have undergone surgery to remove the tumor.
Detailed description
OBJECTIVES:
- Compare disease-free and overall survival of women with early stage breast cancer treated with adjuvant cyclophosphamide, methotrexate, and fluorouracil with or without epirubicin.
- Compare the quality of life in a subgroup of these patients treated with these regimens.
OUTLINE: This is a randomized study. Patients are stratified according to radiotherapy timing (concurrent versus sequential), nodal status (negative versus 1-3 versus at least 4), age (50 and under versus over 50), grade, and tumor size. Patients are randomized to one of two treatment arms.
- Arm I: Patients receive oral cyclophosphamide on days 1-14 and methotrexate IV and fluorouracil IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses.
- Arm II: Patients receive epirubicin IV on day 1 every 3 weeks for 4 courses followed by cyclophosphamide, methotrexate, and fluorouracil, as in arm I, for 4 courses.
Some patients may receive radiotherapy during or after chemotherapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed in a subset of patients (N=500) before chemotherapy starts, at 3 months of treatment, at the end of chemotherapy, and at 6, 12, and 18 months after treatment.
Patients are followed annually for 10 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: Approximately 2,000 patients will be accrued for this study within 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, 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 |
|---|---|---|
| CMF regimen | Drug | – |
| cyclophosphamide | Drug | – |
| epirubicin hydrochloride | Drug | – |
| fluorouracil | Drug | – |
| methotrexate | Drug | – |
| adjuvant therapy | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Not reported in the source record.
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 19 Dec 2013.
- BackgroundEarl H, Hiller L, Dunn JA, et al.: The National Epirubicin Adjuvant Trial (NEAT) and Scottish Cancer Trials Breast Group (SCTBG) br9601 randomized phase III adjuvant early breast cancer trials: the updated definitive joint analysis. [Abstract] J Clin Oncol 25 (Suppl 18): A-534, 11s, 2007.
- Background: PubMed 17079759Poole CJ, Earl HM, Hiller L, Dunn JA, Bathers S, Grieve RJ, Spooner DA, Agrawal RK, Fernando IN, Brunt AM, O'Reilly SM, Crawford SM, Rea DW, Simmonds P, Mansi JL, Stanley A, Harvey P, McAdam K, Foster L, Leonard RC, Twelves CJ; NEAT Investigators and the SCTBG. Epirubicin and cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy for early breast cancer. N Engl J Med. 2006 Nov 2;355(18):1851-62. doi: 10.1056/NEJMoa052084.
- BackgroundPoole CJ, Earl HM, Dunn JA, et al.: NEAT (National Epirubicin Adjuvant Trial) and SCTBG BR9601 (Scottish Cancer Trials Breast Group) phase III adjuvant breast trials show a significant relapse-free and overall survival advantage for sequential ECMF. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-13, 4, 2003.
- Results publication: PubMed 18797468Earl HM, Hiller L, Dunn JA, Bathers S, Harvey P, Stanley A, Grieve RJ, Agrawal RK, Fernando IN, Brunt AM, McAdam K, O'Reilly S, Rea DW, Spooner D, Poole CJ; NEAT Investigators. NEAT: National Epirubicin Adjuvant Trial--toxicity, delivered dose intensity and quality of life. Br J Cancer. 2008 Oct 21;99(8):1226-31. doi: 10.1038/sj.bjc.6604674. Epub 2008 Sep 16.
- Derived from this study: PubMed 25897014Ali HR, Glont SE, Blows FM, Provenzano E, Dawson SJ, Liu B, Hiller L, Dunn J, Poole CJ, Bowden S, Earl HM, Pharoah PD, Caldas C. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol. 2015 Jul;26(7):1488-93. doi: 10.1093/annonc/mdv192. Epub 2015 Apr 20.
- Derived from this study: PubMed 24915873Ali HR, Provenzano E, Dawson SJ, Blows FM, Liu B, Shah M, Earl HM, Poole CJ, Hiller L, Dunn JA, Bowden SJ, Twelves C, Bartlett JM, Mahmoud SM, Rakha E, Ellis IO, Liu S, Gao D, Nielsen TO, Pharoah PD, Caldas C. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol. 2014 Aug;25(8):1536-43. doi: 10.1093/annonc/mdu191. Epub 2014 Jun 9.
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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.
Helena Earl, MBBS, PhD, FRCP study chair
Cambridge University Hospitals NHS Foundation Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CMF regimen, cyclophosphamide and epirubicin hydrochloride in people with Breast Cancer, run by University Hospital Birmingham at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00003577, which also lists 6 linked publications.
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 19 Dec 2013.