FAC Versus FAC Plus Weekly Paclitaxel as Adjuvant Treatment of Node Negative High Risk Breast Cancer Patients

March 3, 2023 updated by: Spanish Breast Cancer Research Group

Multicenter Randomized Phase III Trial to Compare 6 FAC Cycles vs 4 FAC Cycles Followed by 8 Weekly Paclitaxel Administrations, as Adjuvant Treatment for Node Negative Operable Breast Cancer Patients

This is a prospective, open-label, randomized, phase III trial. Patients will be stratified after breast surgery, as per investigational site; menopausal status; node negative diagnosis, as per sentinel-node technique versus lymphadenectomy; hormone receptor status (positive versus negative).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients will be randomized to:

  • Fluorouracil, doxorubicin, and cyclophosphamide (FAC) x 6 (cycles): 5-fluorouracil 500 mg/m2 + doxorubicin 50 mg/m2 + cyclophosphamide 500 mg/m2 day 1, every 3 weeks, for 6 cycles.
  • FAC x 4 (cycles) → Paclitaxel x 8 (cycles): 5-fluorouracil 500 mg/m2 + doxorubicin 50 mg/m2 + cyclophosphamide 500 mg/m2 day 1, every 3 weeks, for 4 cycles, followed by 8 administrations of weekly paclitaxel 100 mg/m2

Premenopausal women with hormone receptor positive tumors must receive tamoxifen 20 mg daily for 5 years, after the end of chemotherapy.

Postmenopausal women with hormone receptor positive tumors are allowed to receive aromatase inhibitors as initial adjuvant hormone therapy or after tamoxifen.

All patients with breast conservative surgery must receive radiotherapy.

Estimated 5-year disease-free survival in the control arm (FAC x 6) is expected to be 80%. It is expected that disease-free survival will increase by 5% in the experimental arm (FAC-paclitaxel). 906 patients per arm must be recruited, to detect this difference with an alpha error of 0.05 and 80% power. Assuming a 6% post-randomization drop-out rate, 960 patients per arm are needed, 1920 in total.

Study Type

Interventional

Enrollment (Actual)

1925

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • A Coruña, Spain, 15009
        • Centro Oncologico de Galicia
      • A Coruña, Spain, 15006
        • Complejo Hospitalario Juan Canalejo
      • Albacete, Spain, 2066
        • Complejo Hospitalario de Albacete
      • Alicante, Spain, 3010
        • Hospital General Universitario de Alicante
      • Alicante, Spain, 3804
        • Hospital Virgen de los Lirios
      • Badalona, Spain, 8916
        • Hospital Germans Trías i Pujol
      • Barcelona, Spain, 8041
        • Hospital de La Santa Creu i Sant Pau
      • Barcelona, Spain, 8003
        • Hospital Del Mar
      • Barcelona, Spain, 8036
        • Hospital Clinic I Provincial
      • Barcelona, Spain, 8017
        • Clínica Corochan S.A.
      • Barcelona, Spain, 8500
        • Hospital General de Vic
      • Bilbao, Spain, 48013
        • Hospital de Basurto
      • Burgos, Spain, 9005
        • Hospital General Yague
      • Cadiz, Spain, 11009
        • Hospital Puerta del Mar
      • Ciudad Real, Spain, 13005
        • Hospital General de Ciudad Real
      • Cuenca, Spain, 16002
        • Hospital Virgen de La Luz
      • Córdoba, Spain, 14004
        • Hospital Reina Sofía
      • Gerona, Spain, 17007
        • ICO Hospital Universitari Josep Trueta
      • Guadalajara, Spain, 19002
        • Hospital General de Guadalajara
      • Jaén, Spain, 23007
        • Complejo Hospitalario de Jaén
      • Lugo, Spain, 27004
        • Hospital Xeral Calde
      • MAdrid, Spain, 28035
        • Hospital Puerta de Hierro
      • Madrid, Spain, 28006
        • Hospital Universitario La Princesa
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal
      • Madrid, Spain, 28046
        • Hospital La Paz
      • Madrid, Spain, 28034
        • Hospital Ruber Internacional
      • Madrid, Spain, 28021
        • Hospital Doce de Octubre
      • Madrid, Spain, 28050
        • CIOCC Hospital Norte-Sanchinarro
      • Murcia, Spain, 30008
        • Hospital Morales Messeguer
      • Málaga, Spain, 29010
        • Hospital Carlos Haya
      • Málaga, Spain, 29010
        • Complejo Hospitalario Virgen de la Victoria
      • Orense, Spain, 32005
        • Hospital Sta María Nai
      • Palencia, Spain, 34005
        • Hospital General Río Carrión
      • Salamanca, Spain, 37007
        • Hospital Clinico Universitario de Salamanca
      • San Sebastián, Spain, 20014
        • Hospital de Donostia
      • San Sebastián, Spain, 20012
        • Instituto Oncológico de Guipúzcoa
      • Santander, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
      • Sevilla, Spain, 41014
        • Hospital Universitario de Valme
      • Sevilla, Spain, 41013
        • Hospital Univ. Virgen del Rocío
      • Toledo, Spain, 45004
        • Hospital Virgen de la Salud
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia
      • Valencia, Spain, 46009
        • Instituto Valenciano de Oncología
      • Valencia, Spain, 46009
        • Hospital Universitario La Fe
      • Valencia, Spain, 46015
        • Hospital Arnau de Vilanova
      • Vitoria, Spain, 1009
        • Hospital Txagorritxu
      • Zamora, Spain, 49021
        • Hospital Provincial de Zamora
      • Zaragoza, Spain, 50009
        • Hospital Miguel Servet
      • Zaragoza, Spain, 50009
        • Hospital Lozano Blesa
    • Alicante
      • Elche, Alicante, Spain, 3203
        • Hospital General Univ. De Elche
      • Elda, Alicante, Spain, 3600
        • Hospital General de Elda
    • Barcelona
      • Manresa, Barcelona, Spain, 8243
        • Complejo Hospitalario de Manresa
      • Sabadell, Barcelona, Spain, 8208
        • Consorci Sanitari Parc Taulí
      • Santa Coloma De Gramenet, Barcelona, Spain, 8923
        • Hospital del Espíritu Santo
      • Terrassa, Barcelona, Spain, 8221
        • Consorci Sanitari Terrassa
      • Terrassa, Barcelona, Spain, 8221
        • Hospital Mutua Terrassa
    • Cadiz
      • Jerez De La Frontera, Cadiz, Spain, 11407
        • Hospital General Jerez de la Frontera
    • Castellón
      • Castellón De La Plana, Castellón, Spain, 12002
        • Hospital Provincial de Castellon
    • Huesca
      • Barbastro, Huesca, Spain, 22300
        • Hospital Comarcal de Barbastro
    • Las Palmas
      • Las Palmas De Gran Canaria, Las Palmas, Spain, 35016
        • Hospital Insular de Gran Canaria
    • MAdrid
      • Alcorcón, MAdrid, Spain, 28922
        • Fundacion Hospital de Alcorcon
      • Móstoles, MAdrid, Spain, 28935
        • Hospital De Mostoles
    • Madrid
      • Boadilla Del Monte, Madrid, Spain, 28660
        • Hospital Madrid- Montepríncipe
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Hospital Virgen de la Arrixaca
    • Pontevedra
      • Vigo, Pontevedra, Spain, 36211
        • Hospital Policlínico Vigo POVISA
    • Santa Cruz De Tenerife
      • La Laguna, Santa Cruz De Tenerife, Spain, 38320
        • Hospital Universitario de Canarias
    • Tarragona
      • Reus, Tarragona, Spain, 43201
        • Hospital Sant Joan de Reus
    • Valencia
      • Alzira, Valencia, Spain, 46600
        • Hospital de la Ribera

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Written informed consent.

  • Histological diagnoses of operable invasive adenocarcinoma of the breast (T1-T3). Tumors must be Human Epidermal Growth Factor Receptor 2 (HER2) negative. Patients must be free of disease in the axilla (node negative). If lymphadenectomy is done, at least 10 nodes must be examined. If sentinel node technique is used, sentinel node must be free of disease. Patients must present at least one high risk criterion (St. Gallen, 1998) as follows:

    • Tumor size > 2 cm; and/or
    • ER and Progesterone Receptor (PgR) negative; and/or
    • Histological grade 2-3; and/or
    • Age < 35 years old.
  • Time window between surgery and study randomization must be less than 60 days.
  • Surgery must consist of mastectomy or conservative surgery. Margins free of disease and ductal carcinoma in situ (DCIS) are required. Lobular carcinoma is not considered a positive margin.
  • Patients must not present evidence of metastatic disease.
  • Status of hormone receptors in primary tumor. Results must be available before the end of adjuvant chemotherapy.
  • Status of HER2 in primary tumor, known before randomization. Patients with Immunohistochemistry (IHC) 0 or +1 are eligible. For patients with IHC 2+, fluorescent in situ hybridization (FISH) is mandatory and result must be negative.
  • Age >= 18 and <= 70 years old.
  • Performance status (Karnofsky index) >= 80.
  • Normal electrocardiogram (EKG) in the 12 weeks prior to randomization. If needed, normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF).

  • Laboratory results (within 14 days prior to randomization):

    • Hematology: neutrophils >= 1.5 x 10^9/l; platelets >= 100x 10^9/l; hemoglobin >= 10 mg/dl;
    • Hepatic function: total bilirubin <= 1 upper normal limit (UNL); Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <= 2.5 UNL; alkaline phosphatase <= 2.5 UNL. If values of AST and ALT > 1.5 UNL are associated with alkaline phosphatase > 2.5 UNL, patient is not eligible.
    • Renal function: creatinine <= 175 mmol/l (2 mg/dl); creatinine clearance >= 60 ml/min.
  • Complete stage workup during the 12 weeks prior to randomization (mammograms are allowed within a 20 week time window). All patients must have a bilateral mammogram, thorax x-ray, abdominal echography and/or computed tomography (CT)-scan. If bone pain, and/or alkaline phosphatase elevation, a bone scintigraphy is mandatory. This test is recommended for all patients. Other tests, as clinically indicated.
  • Patients able to comply with treatment and study follow-up.
  • Negative pregnancy test done in the 14 previous days to randomization.

Exclusion Criteria:

  • Prior systemic therapy for breast cancer.
  • Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any malignancy.
  • Prior radiotherapy for breast cancer.
  • Bilateral invasive breast cancer.
  • Pregnant or lactating women. Adequate contraceptive methods must be used during chemotherapy and hormone therapy treatments. Negative pregnancy test in the 14 previous days to randomization.
  • Any T4 or N1-3 or M1 tumor.
  • HER2 positive breast cancer (IHC 3+ or positive FISH result).
  • Pre-existing grade >=2 motor or sensorial neurotoxicity by the National Cancer Institute Common Toxicity Criteria (NCICTC) v-2.0.
  • Any other serious medical pathology, such as congestive heart failure, unstable angina, history of myocardial infarction during the previous year, uncontrolled hypertension or high risk arrhythmias.
  • History of neurological or psychiatric disorders, which could preclude the patients to free informed consent.
  • Active uncontrolled infection.
  • Active peptic ulcer; unstable diabetes mellitus.
  • Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.
  • Concomitant treatment with other investigational products. Participation in other clinical trials with a non-marketed drug in the 20 previous days before randomization.
  • Concomitant treatment with other therapy for cancer.
  • Males.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A: FAC
FAC X 6 The standard arm consisted of six cycles of FAC (fluorouracil 500 mg/m2, doxorubicin 50mg/m2, and cyclophosphamide 500mg/m2) administered once every 3 weeks.
Drug: Fluorouracil
Arm A: FAC Arm B: FAC-wP
Other Names:
  • Adrucil
Drug: Doxorubicin
Arm A: FAC Arm B: FAC-wP
Other Names:
  • Caelyx
Drug: Cyclophosphamide
Arm A: FAC Arm B: FAC-wP
Other Names:
  • Cytoxan
Experimental: Arm B: FAC-wP
FAC X 4 + 8 weekly Paclitaxel (wP) Patients in the experimental arm received four cycles of the FAC regimen followed by eight weekly administrations of paclitaxel (100mg/m2 per dose)
Drug: Fluorouracil
Arm A: FAC Arm B: FAC-wP
Other Names:
  • Adrucil
Drug: Doxorubicin
Arm A: FAC Arm B: FAC-wP
Other Names:
  • Caelyx
Drug: Cyclophosphamide
Arm A: FAC Arm B: FAC-wP
Other Names:
  • Cytoxan
Drug: Paclitaxel
Arm B: FAC-wP
Other Names:
  • taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free Survival (DFS) Event
Time Frame: Up to 5 years
DFS is defined as the evidence of local, regional or metastatic recurrence, second primary cancer (with the exception of carcinoma of squamous cells or basal cells of the skin, cervical carcinoma in situ or lobular or ductal carcinoma in situ of the breast) or death for any reason.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) Event
Time Frame: Up to 5 years
OS event is defined as the death from any cause.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spanish Breast Cancer Research Group

Collaborators

Bristol-Myers Squibb

Investigators

  • Study Director: Study Director, Hospital Universitario San Carlos

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 19, 2003

Primary Completion (Actual)

October 1, 2013

Study Completion (Actual)

October 1, 2013

Study Registration Dates

First Submitted

August 10, 2005

First Submitted That Met QC Criteria

August 10, 2005

First Posted (Estimate)

August 11, 2005

Study Record Updates

Last Update Posted (Estimate)

March 7, 2023

Last Update Submitted That Met QC Criteria

March 3, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEICAM 2003-02
  • 2005-003109-10 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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