Combination Chemotherapy With or Without Fluorouracil and/or Pegfilgrastim in Treating Women With Node-Positive Breast Cancer
Primary Purpose
Breast Cancer
Status
Active
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
pegfilgrastim
cyclophosphamide
epirubicin hydrochloride
fluorouracil
paclitaxel
adjuvant therapy
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed primary breast cancer
- No histology other than carcinoma
Node-positive disease
- Must have at least 1 involved axillary node or internal mammary node
Previously resected disease
- Has undergone radical surgery (i.e., mastectomy or conservative surgery) with axillary node dissection within the past 7 weeks
- No inflammatory carcinoma
- No prior or concurrent ipsilateral or contralateral invasive breast carcinoma
- No metastatic disease, including metastasis in the ipsilateral supraclavicular lymph nodes
- Hormone receptor status not specified
PATIENT CHARACTERISTICS:
- Female
- Menopausal status not specified
- ECOG performance status 0-1
- Absolute neutrophil count ≥ 1,500/mm³
- WBC ≥ 4,000/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Creatinine ≤ 1.5 times ULN
- AST and ALT ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No chronic liver or renal disease
- No other serious medical illness requiring medication
- No other malignancy except adequately treated, cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin
- No symptomatic peripheral neuropathy > grade 2
- No hypersensitivity to study drugs or their components
- No recent myocardial infarction, congestive heart failure, or serious arrhythmia
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior chemotherapy
- No prior cytotoxic regimens
- No prior radiation therapy, except for intraoperative radiation therapy
Sites / Locations
Outcomes
Primary Outcome Measures
Disease-free survival
Secondary Outcome Measures
Overall survival
Toxicity
Full Information
NCT ID
NCT00433420
First Posted
February 8, 2007
Last Updated
May 17, 2022
Sponsor
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Collaborators
Gruppo Italiano Mammella (GIM)
1. Study Identification
Unique Protocol Identification Number
NCT00433420
Brief Title
Combination Chemotherapy With or Without Fluorouracil and/or Pegfilgrastim in Treating Women With Node-Positive Breast Cancer
Official Title
A Phase III Randomized Study of EC Followed by Paclitaxel Versus FEC Followed by Paclitaxel, All Given Either Every 3 Weeks or 2 Weeks Supported by Pegfilgrastim, for Node Positive Breast Cancer Patients
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 2003 (Actual)
Primary Completion Date
May 2006 (Actual)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Collaborators
Gruppo Italiano Mammella (GIM)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as epirubicin, cyclophosphamide, paclitaxel, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving combination chemotherapy and pegfilgrastim after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy is more effective with or without fluorouracil and/or pegfilgrastim in treating breast cancer.
PURPOSE: This randomized phase III trial is studying combination chemotherapy to compare how well it works when given with or without fluorouracil and/or pegfilgrastim in treating women with node-positive breast cancer.
Detailed Description
OBJECTIVES:
Primary
Compare the efficacy of adjuvant therapy comprising epirubicin hydrochloride, cyclophosphamide, and paclitaxel with vs without fluorouracil and/or pegfilgrastim in women with node-positive breast cancer.
Secondary
Compare the overall survival of patients treated with these regimens.
Compare the safety of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.
Arm I: Patients receive epirubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive paclitaxel IV over 3 hours on day 1. Treatment with paclitaxel repeats every 3 weeks for 4 courses.
Arm II: Patients receive fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive paclitaxel as in arm I.
Arm III: Patients receive epirubicin hydrochloride IV and cyclophosphamide IV on day 1 and pegfilgrastim subcutaneously (SC) on day 4. Treatment repeats every 2 weeks for 4 courses. Patients then receive paclitaxel IV over 3 hours on day 1 and pegfilgrastim subcutaneously (SC) on day 4. Treatment with paclitaxel and pegfilgrastim repeats every 2 weeks for 4 courses.
Arm IV: Patients receive fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 4. Treatment repeats every 2 weeks for 4 courses. Patients then receive paclitaxel and pegfilgrastim as in arm III.
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of chemotherapy with or without pegfilgrastim, patients may undergo external-beam radiation therapy at the discretion of treating center. Patients with positive estrogen and/or progesterone receptor tumor receive tamoxifen for 5 years.
After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 2,000 patients will be accrued for this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Allocation
Randomized
Enrollment
2000 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
pegfilgrastim
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
epirubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Type
Procedure
Intervention Name(s)
adjuvant therapy
Primary Outcome Measure Information:
Title
Disease-free survival
Secondary Outcome Measure Information:
Title
Overall survival
Title
Toxicity
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed primary breast cancer
No histology other than carcinoma
Node-positive disease
Must have at least 1 involved axillary node or internal mammary node
Previously resected disease
Has undergone radical surgery (i.e., mastectomy or conservative surgery) with axillary node dissection within the past 7 weeks
No inflammatory carcinoma
No prior or concurrent ipsilateral or contralateral invasive breast carcinoma
No metastatic disease, including metastasis in the ipsilateral supraclavicular lymph nodes
Hormone receptor status not specified
PATIENT CHARACTERISTICS:
Female
Menopausal status not specified
ECOG performance status 0-1
Absolute neutrophil count ≥ 1,500/mm³
WBC ≥ 4,000/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Creatinine ≤ 1.5 times ULN
AST and ALT ≤ 2.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No chronic liver or renal disease
No other serious medical illness requiring medication
No other malignancy except adequately treated, cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin
No symptomatic peripheral neuropathy > grade 2
No hypersensitivity to study drugs or their components
No recent myocardial infarction, congestive heart failure, or serious arrhythmia
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
No prior chemotherapy
No prior cytotoxic regimens
No prior radiation therapy, except for intraoperative radiation therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marco Venturini, MD
Organizational Affiliation
IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Official's Role
Study Chair
12. IPD Sharing Statement
Citations:
PubMed Identifier
36370716
Citation
Del Mastro L, Poggio F, Blondeaux E, De Placido S, Giuliano M, Forestieri V, De Laurentiis M, Gravina A, Bisagni G, Rimanti A, Turletti A, Nistico C, Vaccaro A, Cognetti F, Fabi A, Gasparro S, Garrone O, Alicicco MG, Urracci Y, Mansutti M, Poletti P, Correale P, Bighin C, Puglisi F, Montemurro F, Colantuoni G, Lambertini M, Boni L; Gruppo Italiano Mammella Investigators. Fluorouracil and dose-dense adjuvant chemotherapy in patients with early-stage breast cancer (GIM2): end-of-study results from a randomised, phase 3 trial. Lancet Oncol. 2022 Dec;23(12):1571-1582. doi: 10.1016/S1470-2045(22)00632-5. Epub 2022 Nov 10.
Results Reference
derived
PubMed Identifier
26306520
Citation
Lambertini M, Bruzzi P, Poggio F, Pastorino S, Gardin G, Clavarezza M, Bighin C, Pronzato P, Del Mastro L. Pegfilgrastim administration after 24 or 72 or 96 h to allow dose-dense anthracycline- and taxane-based chemotherapy in breast cancer patients: a single-center experience within the GIM2 randomized phase III trial. Support Care Cancer. 2016 Mar;24(3):1285-94. doi: 10.1007/s00520-015-2907-2. Epub 2015 Aug 27.
Results Reference
derived
PubMed Identifier
25740286
Citation
Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nistico C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (GIM) investigators. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 x 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. doi: 10.1016/S0140-6736(14)62048-1. Epub 2015 Mar 2.
Results Reference
derived
Learn more about this trial
Combination Chemotherapy With or Without Fluorouracil and/or Pegfilgrastim in Treating Women With Node-Positive Breast Cancer
We'll reach out to this number within 24 hrs