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

NCT ID: NCT00070278

Last Updated: 2013-08-07

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

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Breast Cancer

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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cyclophosphamide

Intervention Type DRUG

epirubicin hydrochloride

Intervention Type DRUG

gemcitabine hydrochloride

Intervention Type DRUG

paclitaxel

Intervention Type DRUG

comparative genomic hybridization

Intervention Type GENETIC

microarray analysis

Intervention Type GENETIC

mutation analysis

Intervention Type GENETIC

conventional surgery

Intervention Type PROCEDURE

neoadjuvant therapy

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion 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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role lead

Principal Investigators

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Helena Earl, MBBS, PhD, FRCP

Role:

Cambridge University Hospitals NHS Foundation Trust

Locations

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Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 26882907 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26715442 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24360787 (View on PubMed)

Other Identifiers

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CDR0000331863

Identifier Type: REGISTRY

Identifier Source: secondary_id

EU-20316

Identifier Type: -

Identifier Source: secondary_id

CRUK-neo-tAnGo

Identifier Type: -

Identifier Source: org_study_id