Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Followed by Radiation Therapy With or Without Surgery in Treating Women With Locally Advanced or Inflammatory Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	70 and under	Other	EORTC-10994 ACCOG-EORTC-10994, SAKK-EORTC-10994, SBGC-EORTC-10994, BIG-1-00, NCT00017095

Objectives

1. Compare neoadjuvant fluorouracil, epirubicin, and cyclophosphamide vs docetaxel and epirubicin followed by radiotherapy and surgery in women with locally advanced, inflammatory, or large operable breast cancer.
2. Compare the progression-free survival of patients treated with these regimens.
3. Compare the distant metastasis-free survival and survival of patients treated with these regimens.
4. Compare the clinical and pathological responses to these regimens in these patients.
5. Compare the toxicity of these regimens in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed breast cancer
  • Locally advanced or inflammatory disease
    • T4a-d, any N, M0

      OR

    • Any T, N2 or N3, M0
    • Large operable T2 or T3 tumors



• No bilateral breast cancer



• Frozen tumor sample available
  • 1 incisional biopsy

    OR

  • 2 trucut biopsies from a 14G needle



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Patient Characteristics:

Age:

• 70 and under

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count greater than 1,500/mm³
• Platelet count greater than 100,000/mm³

Hepatic:

• Bilirubin less than 1.2 mg/dL
• SGOT less than 60 IU/L

Renal:

• Creatinine less than 1.35 mg/dL

Cardiovascular:

• LVEF normal by echocardiography or MUGA

Other:

• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No serious uncontrolled medical condition
• No uncontrolled psychiatric or addictive disorders
• Not pregnant or nursing
• Fertile patients must use effective contraception

Expected Enrollment

A total of 1,850 patients will be accrued for this study within 5.5 years.

Outcomes

Progression-free survival

Distant metastasis-free survival
Overall survival
Pathological response
Clinical response by RECIST without pathologic response
Toxicity measured by CTC v2.0

Outline

This is a randomized, multicenter study. Patients are stratified according to stage of disease (large T2-3 vs locally advanced or inflammatory), p53 status (negative vs positive vs unknown), and participating center. Patients are randomized to 1 of 2 chemotherapy treatment arms.

• Arm I: Patients receive 1 of 3 chemotherapy regimens comprising fluorouracil, epirubicin, and cyclophosphamide (FEC) (according to participating institution).
  • FEC 100: Patients receive fluorouracil IV over 15 minutes, epirubicin IV over 1 hour, and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Canadian FEC: Patients receive oral cyclophosphamide on days 1-14 and epirubicin IV and fluorouracil IV on days 1 and 8. If oral medications are not tolerated, patients may switch to cyclophosphamide IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Tailored FEC: Patients receive fluorouracil IV over 15 minutes, epirubicin IV over 1 hour, and cyclophosphamide IV over 1-2 hours on day 1. Patients also receive filgrastim (G-CSF) subcutaneously on days 2-15 or until blood counts recover. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.



• Arm II: Patients receive docetaxel IV over 1 hour on days 1, 22, and 43 followed by epirubicin IV over 15 minutes and docetaxel IV over 1 hour on days 64, 85, and 106 in the absence of disease progression or unacceptable toxicity.

Following chemotherapy, patients may undergo loco-regional therapy comprising radiotherapy with or without breast conservation surgery or mastectomy. Patients with estrogen- and/or progesterone-receptor-positive disease also receive tamoxifen or an aromatase inhibitor for 5 years.

Patients are followed every 3 months for 1 year, every 4 months for 1.5 years, and then every 6 months thereafter.

Bonnefoi H, Zimmer AS, Piccart M, et al.: P53 functional assay in yeast: evaluation in 1856 patients in a large prospective clinical trial: EORTC 10994/BIG 00-01. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-1067, 2008.

Bonnefoi H, Potti A, Delorenzi M, et al.: Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial. Lancet Oncol 8 (12): 1071-8, 2007.[PUBMED Abstract]

Karina M, Bogaerts J, Piccart M, et al.: Preliminary safety data of the EORTC 10994/BIG 00-01 neoadjuvant trial comparing 3 cycles of docetaxel followed by 3 cycles of epirubicin-docetaxel versus 6 cycles of FEC 100 in patients with locally advanced/inflammatory or large operable breast cancer. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3067, S146-7, 2006.

Bonnefoi H, Farmer P, Delorenzi M, et al.: Is there a regimen-specific gene signature predicting for pathological complete response after neoadjuvant chemotherapy in hormone-negative breast cancer patients? A microarray substudy of 101 patients included in EORTC 10994/BIG 00-01 trial. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-1040, 2005.

Farmer P, Iggo R, Becette V, et al.: High quality gene expression microarray data from a multicentre prospective trial: results of the first microarray analysis in the EORTC 10994/ BIG 00-01 study. [Abstract] Eur J Cancer 2 (Suppl 3): A-155, 99, 2004.

Trial Contact Information

Trial Lead Organizations

European Organization for Research and Treatment of Cancer

Herve Bonnefoi, MD, Study coordinator		Ph: 41-22-382-3311 Email: herve.bonnefoi@hcuge.ch

Swedish Breast Cancer Group

Jonas Bergh, MD, PhD, Protocol chair		Ph: 46-8-517-762-79

Swiss Group for Clinical Cancer Research

Barbara Muster, Protocol chair		Ph: 41-31-389-9191

Anglo Celtic Cooperative Oncology Group

Kirsten Murray, Protocol chair		Ph: 00-44-131-551-8481 Email: kirsten.murray@isd.csa.scot.nhs.uk

Registry Information
Official Title		First Prospective Intergroup Translational Research Trial Assessing the Potential Predictive Value of p53 Using a Functional Assay in Yeast in Patients with Locally Advanced/Inflammatory or Large Operable Breast Cancer Prospectively Randomised to a Taxane Versus a Non Taxane Regimen
Trial Start Date		2001-03-14
Registered in ClinicalTrials.gov		NCT00017095 1
Date Submitted to PDQ		2001-04-03
Information Last Verified		2006-11-19

Table of Links

1	http://clinicaltrials.gov/ct/show/NCT00017095