Neoadjuvant Epirubicin, Cyclophosphamide, and Paclitaxel With or Without Gemcitabine in Treating Women Who Are Undergoing Surgery for Early Breast Cancer

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ClinicalTrials.gov Identifier: NCT00070278

Recruitment Status : Unknown

Verified January 2009 by National Cancer Institute (NCI).
Recruitment status was: Active, not recruiting

First Posted : October 7, 2003

Last Update Posted : August 7, 2013

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by:

National Cancer Institute (NCI)

Study Description

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as epirubicin, cyclophosphamide, paclitaxel, and gemcitabine use different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy before surgery may shrink the tumor so that it can be removed during surgery. It is not yet known which combination chemotherapy regimen is more effective in treating early breast cancer.

PURPOSE: This randomized phase III trial is studying different regimens of combination chemotherapy to compare how well they work in treating women who are undergoing surgery for early invasive breast cancer.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: cyclophosphamide Drug: epirubicin hydrochloride Drug: gemcitabine hydrochloride Drug: paclitaxel Genetic: comparative genomic hybridization Genetic: microarray analysis Genetic: mutation analysis Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase 3

Detailed Description:

OBJECTIVES:

Primary

Compare the complete pathological response rate in women with poor-risk early breast cancer treated with neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel with vs without gemcitabine.

Secondary

Compare the disease-free and overall survival of patients treated with these regimens.
Compare the toxicity of these regimens in these patients.
Compare the effect of these regimens on prognostic factors in these patients.
Correlate molecular profiles, specific gene mutations, and genomic and gene expression changes with clinical outcome in these patients.
Compare the quality of life of patients treated with these regimens.
Determine the health economics associated with this study.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to estrogen-receptor status (negative vs greater than 10% positive cells), HER-2 status (positive vs negative), tumor size (30-50 mm vs greater than 50 mm), and clinical involvement of axillary nodes (yes vs no). Patients are randomized to 1 of 4 treatment arms.

Neoadjuvant sequential chemotherapy:
- Arm I: Patients receive epirubicin IV and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Patients then receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for 4 courses.
- Arm II: Patients receive paclitaxel as in arm I followed by epirubicin and cyclophosphamide as in arm I.
- Arm III: Patients receive epirubicin and cyclophosphamide as in arm I followed by paclitaxel as in arm I and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses.
- Arm IV: Patients receive paclitaxel as in arm I and gemcitabine as in arm III followed by epirubicin and cyclophosphamide as in arm I.
Surgery: After completion of neoadjuvant chemotherapy, patients in all arms undergo definitive surgery.

Tumor tissue is removed from a subset of patients during serial biopsies. Molecular and genetic profiling, mutation analysis, and comparative genomic analysis is performed on the tissue samples.

Quality of life is assessed at baseline, after 4 courses of chemotherapy, after the completion of chemotherapy, after surgery, and then every 6 months for 2 years.

Patients are followed every 2 months for 2 years and then every 3 months for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 800 patients (200 per treatment arm) will be accrued for this study.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	800 participants
Allocation:	Randomized
Primary Purpose:	Treatment
Official Title:	A Phase III Randomized Neoadjuvant Study of Sequential Epirubicin/Cyclophosphamide and Paclitaxel + - Gemcitabine in Poor Risk Early Breast Cancer
Study Start Date :	January 2005
Actual Primary Completion Date :	September 2007

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Breast cancer

MedlinePlus related topics: Breast Cancer

Drug Information available for: Cyclophosphamide Epirubicin hydrochloride Epirubicin Gemcitabine

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

Complete pathological response after 4 courses

Secondary Outcome Measures :

Survival
Disease-free survival
Effect of prognostic factors

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed invasive breast cancer
- Grade 2 or 3
Tumor size at least 3 cm by ultrasound
No evidence of metastatic disease
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age

Not specified

Sex

Female

Menopausal status

Not specified

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Not specified

Renal

Not specified

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Fit to receive study chemotherapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00070278

Locations

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United Kingdom
Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, United Kingdom, CB2 2QQ

Sponsors and Collaborators

Cambridge University Hospitals NHS Foundation Trust

Investigators

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OverallOfficial:	Helena Earl, MBBS, PhD, FRCP	Cambridge University Hospitals NHS Foundation Trust

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ali HR, Dariush A, Provenzano E, Bardwell H, Abraham JE, Iddawela M, Vallier AL, Hiller L, Dunn JA, Bowden SJ, Hickish T, McAdam K, Houston S, Irwin MJ, Pharoah PD, Brenton JD, Walton NA, Earl HM, Caldas C. Computational pathology of pre-treatment biopsies identifies lymphocyte density as a predictor of response to neoadjuvant chemotherapy in breast cancer. Breast Cancer Res. 2016 Feb 16;18(1):21. doi: 10.1186/s13058-016-0682-8.

Abraham JE, Hiller L, Dorling L, Vallier AL, Dunn J, Bowden S, Ingle S, Jones L, Hardy R, Twelves C, Poole CJ, Pharoah PD, Caldas C, Earl HM. A nested cohort study of 6,248 early breast cancer patients treated in neoadjuvant and adjuvant chemotherapy trials investigating the prognostic value of chemotherapy-related toxicities. BMC Med. 2015 Dec 29;13:306. doi: 10.1186/s12916-015-0547-5.

Earl HM, Vallier AL, Hiller L, Fenwick N, Young J, Iddawela M, Abraham J, Hughes-Davies L, Gounaris I, McAdam K, Houston S, Hickish T, Skene A, Chan S, Dean S, Ritchie D, Laing R, Harries M, Gallagher C, Wishart G, Dunn J, Provenzano E, Caldas C; Neo-tAnGo Investigators. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2x2 factorial randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):201-12. doi: 10.1016/S1470-2045(13)70554-0. Epub 2013 Dec 19.

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ClinicalTrials.gov Identifier:	NCT00070278
Other Study ID Numbers:	CRUK-neo-tAnGo CDR0000331863 ( Registry Identifier: PDQ (Physician Data Query) ) EU-20316
First Posted:	October 7, 2003 Key Record Dates
Last Update Posted:	August 7, 2013
Last Verified:	January 2009

Keywords provided by National Cancer Institute (NCI):


stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer

Additional relevant MeSH terms:

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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Cyclophosphamide Gemcitabine Epirubicin Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators	Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Myeloablative Agonists Antimetabolites, Antineoplastic Antimetabolites Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors

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