Dose-adjusted Adjuvant FEC Compared to Standard FEC for Breast Cancer

SBG 2000-1. Individually Dose-adjusted FEC Compared to Standard FEC as Adjuvant Chemotherapy for Node Positive or High-risk Node Negative Breast Cancer. A Randomized Study by the Scandinavian Breast Group

This is an open randomized phase III study. The primary objective of this study is to compare FEC adjuvant chemotherapy in operable breast cancer given either as fixed doses calculated according to the patients surface area or with doses adjusted according to leukopenia after course one in order to achieve hematological equitoxicity. The main aim of the study is to test whether chemotherapy dosage aimed at hematological equitoxicity will improve the effect of adjuvant chemotherapy.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: 5-FU, epirubicin and cyclophosphamide

Detailed Description

Group A, FECStandard(standard FEC) is given 7 courses of 5-fluorouracil-epirubicin (Farmorubicin)-cyclophosphamide with doses based on the patient's surface area. Leukocyte nadir values at day 10, 12 or 13 and 15 are measured. Dose-reductions of one step according to table 8.2.1 are performed in case of leukopenic fever or grade 4 leukopenia.

Group B FECTailored(Tailored FEC) receives course one at identical doses to group A. Leukocyte nadir values at day 10,12 or 13 and 15 are measured. Doses of subsequent courses are adjusted to achieve grade 3 leukopenia (leukocyte nadir 1.0 to 2.0) in patients experiencing only grade 0 to 2 leukopenia after course one.

Dose-reductions of one step according to table 8.2.1 are performed in case of leukopenic fever or grade 4 leukopenia .

Patients achieving only grade 0-2 leukopenia at the first course will be randomized into continued treatment at standard doses (Group A) or to doses tailored to achieve grade 3 leukopenia (Group B). The primary comparisons will be made between these two groups of patients.

Patients with grade 3-4 leukopenia after the first course not be randomized but followed according to the protocol and received treatment as group A, FECStandard.

• Study Type: Interventional
• Enrollment (Actual): 1535
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Node positive or 2) High-risk node negative#
• no major cardiovascular morbidity
• female age 18-60
• ECOG/WHO performance status <1
• histologically proven invasive breast cancer
• written or oral witnessed informed consent according to the local Ethics Committee requirements
• start of adjuvant chemotherapy within 8 weeks after surgery

Exclusion Criteria:

• distant metastases (M1)
• locally advanced cancer
• nonradically operated (positive resection margins)
• pregnancy or lactation
• leukocyte count < 3.5 x109 /l
• platelets < 100 x109 /l
• other serious medical condition
• previous or concurrent malignancies at other sites, except basal cell carcinoma and carcinoma cervicis uteri in situ

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard; Standard FEC (F600, E60, C600) every 3rd week.	Drug: 5-FU, epirubicin and cyclophosphamide; Tailored dose escalation of epirubicin and cyclophosphamide.
Experimental: Tailored; Tailored FEC (F600, E75-90, C900-1200) every 3rd week.	Drug: 5-FU, epirubicin and cyclophosphamide; Tailored dose escalation of epirubicin and cyclophosphamide.
Active Comparator: Registered; Non-randomized arm with patients with grade 3-4 leukopenia after first cycle and treated with standard FEC (F600, E60, C600) every 3rd week.	Drug: 5-FU, epirubicin and cyclophosphamide; Tailored dose escalation of epirubicin and cyclophosphamide.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distant disease-free survival.	Distant disease-free survival comparing standard and tailored arm.	5-10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regio-locally relapsed disease	Regiolocal disease-free survival	5-10 years
Overall survival	Overall survival	5-10 years
Toxicity of treatment.	Adverse events	5-10 years
Leukopenia and correlation to prognosis in distant disease-free survival.	Distant disease-free survival in patients groups based on nadir leukopenia after third cycle.	5-10 years.
Effect of dose escalation of leukopenia and correlation to prognosis in distant disease-free survival.	Comparing distant disease-free survival difference between patients randomized to tailored and dose-escalated FEC with the Group of patients with standard FEC but with similar grade of leukopenia.	5-10 years.

Collaborators and Investigators

• Sponsor: Henrik Lindman
• Collaborators: Scandinavian Breast Group; Danish Breast Cancer Cooperative Group; Swedish Breast Cancer Group; Swedish Cancer Society; Swedish Cancer Foundation; Pharmacia Pharmaceutical Company

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2001
• Primary Completion (Actual): August 1, 2003
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: March 22, 2019
• First Submitted That Met QC Criteria: March 22, 2019
• First Posted (Actual): March 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 28, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Epirubicin
• Other Study ID Numbers: SBG 2000-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Sharing with EBCTCG (Early Breast Cancer Trialists' Collaborative Group).
• IPD Sharing Time Frame: After 5 years.
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No