Combination Chemotherapy With or Without Fluorouracil and/or Pegfilgrastim in Treating Women With Node-Positive Breast Cancer

• ClinicalTrials.gov Identifier: NCT00433420
• Recruitment Status: Active, not recruiting
• First Posted: February 12, 2007
• Last Update Posted: May 18, 2022
• Sponsor: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
• Collaborator: Gruppo Italiano Mammella (GIM)
• Information provided by (Responsible Party): Lucia Del Mastro,MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Biological: pegfilgrastim; Drug: cyclophosphamide; Drug: epirubicin hydrochloride; Drug: fluorouracil; Drug: paclitaxel; Procedure: adjuvant therapy	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 2000 participants
• Allocation: Randomized
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 2003
• Actual Primary Completion Date: May 2006
• Estimated Study Completion Date: December 2025

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Disease-free survival

Secondary Outcome Measures :

1. Overall survival
2. Toxicity

Eligibility Criteria

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

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

Contacts and Locations

Sponsors and Collaborators

IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Gruppo Italiano Mammella (GIM)

Investigators

• Study Chair: Marco Venturini, MD; IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

• Responsible Party: Lucia Del Mastro,MD, MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
• ClinicalTrials.gov Identifier: NCT00433420
• Other Study ID Numbers: GIM-2; CDR0000528056 ( Registry Identifier: PDQ (Physician Data Query) ); EU-20681
• First Posted: February 12, 2007
• Last Update Posted: May 18, 2022
• Last Verified: May 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lucia Del Mastro,MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:

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

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Cyclophosphamide; Fluorouracil; Epirubicin; 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; Antimetabolites; Antimetabolites, Antineoplastic; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors