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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00129389
Recruitment Status : Completed
First Posted : August 11, 2005
Results First Posted : July 12, 2019
Last Update Posted : July 12, 2019
Bristol-Myers Squibb
Information provided by (Responsible Party):
Spanish Breast Cancer Research Group

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Fluorouracil Drug: Doxorubicin Drug: Cyclophosphamide Drug: Paclitaxel Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1925 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 19, 2003
Actual Primary Completion Date : October 1, 2013
Actual Study Completion Date : October 1, 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

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 Name: Adrucil

Drug: Doxorubicin
Arm A: FAC Arm B: FAC-wP
Other Name: Caelyx

Drug: Cyclophosphamide
Arm A: FAC Arm B: FAC-wP
Other Name: 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 Name: Adrucil

Drug: Doxorubicin
Arm A: FAC Arm B: FAC-wP
Other Name: Caelyx

Drug: Cyclophosphamide
Arm A: FAC Arm B: FAC-wP
Other Name: Cytoxan

Drug: Paclitaxel
Arm B: FAC-wP
Other Name: taxol

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Overall Survival (OS) Event [ Time Frame: Up to 5 years ]
    OS event is defined as the death from any cause.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT00129389

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Sponsors and Collaborators
Spanish Breast Cancer Research Group
Bristol-Myers Squibb
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Study Director: Study Director Hospital Universitario San Carlos
Additional Information:
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Responsible Party: Spanish Breast Cancer Research Group Identifier: NCT00129389    
Other Study ID Numbers: GEICAM 2003-02
2005-003109-10 ( EudraCT Number )
First Posted: August 11, 2005    Key Record Dates
Results First Posted: July 12, 2019
Last Update Posted: July 12, 2019
Last Verified: April 2019
Keywords provided by Spanish Breast Cancer Research Group:
Node negative, high risk breast cancer.
Prognostic gene profile.
Saint Gallen high risk criteria.
Weekly paclitaxel.
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
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
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites, Antineoplastic