Combination Chemotherapy With or Without Epirubicin in Treating Women With Stage I or Stage II Breast Cancer

NCT ID: NCT00003577

Last Updated: 2013-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2000 participants

Study Classification

INTERVENTIONAL

Study Start Date

1996-03-31

Study Completion Date

2008-09-30

Brief Summary

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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

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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

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Breast Cancer

Keywords

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stage I breast cancer stage II breast cancer

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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CMF regimen

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

epirubicin hydrochloride

Intervention Type DRUG

fluorouracil

Intervention Type DRUG

methotrexate

Intervention Type DRUG

adjuvant therapy

Intervention Type PROCEDURE

radiation therapy

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Birmingham

OTHER

Sponsor Role lead

Principal Investigators

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Helena Earl, MBBS, PhD, FRCP

Role: STUDY_CHAIR

Cambridge University Hospitals NHS Foundation Trust

Locations

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University of Cambridge

Cambridge, England, United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 17079759 (View on PubMed)

Poole 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.

Reference Type BACKGROUND

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.

Reference Type RESULT
PMID: 18797468 (View on PubMed)

Ali 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.

Reference Type DERIVED
PMID: 25897014 (View on PubMed)

Ali 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.

Reference Type DERIVED
PMID: 24915873 (View on PubMed)

Other Identifiers

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CRC-TU-NEAT

Identifier Type: -

Identifier Source: secondary_id

EU-98041

Identifier Type: -

Identifier Source: secondary_id

CDR0000066644

Identifier Type: -

Identifier Source: org_study_id