Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Dose dense doxorubicin and cyclophosphamide for 4 cycles during the first 8 weeks followed by eribulin mesylate 1.4mg/m2 for 4 cycles during the next 12 weeks.

eribulin mesylate

The purpose of this study is to assess the feasibility of dose-dense doxorubicin and cyclophosphamide followed by eribulin mesylate for adjuvant treatment of early stage breast cancer.

This is a multicenter, single-arm Phase II trial to assess the feasibility of dose-dense adjuvant chemotherapy in subjects with early stage (I-III), HER-2 normal breast cancer. A total of 80 adult subjects will be enrolled in order to have 73 subjects who start the eribulin portion of the adjuvant study regimen. After completion of 4 cycles of AC, each subject will begin 4 cycles of eribulin mesylate 1.4 mg/m2 intravenously over 2 to 5 minutes on Days 1 and 8 of every 21 day cycle.

Dose Dense Doxorubucin and Cyclophosphamide Followed by Eribulin Mesylate for the Adjuvant Treatment of Early Stage Breast Cancer

A Phase II, Single-Arm, Feasibility Study of Dose Dense Doxorubicin and Cyclophosphamide (AC) Followed by Eribulin Mesylate for the Adjuvant Treatment of Early Stage Breast Cancer

The regimen was considered feasible if the participant was able to complete the eribulin portion without dose delay or reduction. Dose delay was defined as a delay due to eribulin-related adverse event (AE) for more than 2 days for subsequent doses (cycles after the initiation of full dose of eribulin, except holidays, scheduling difficulties and nonclinical logistical issues). If a participant had more than 1 dose omission, delay or reduction due to eribulin-related AE, these events were collectively counted as one entity in the same participant. Participants were followed for approximately 3 years after the last dose of the study treatment. Feasibility rates were calculated with or without growth factor support. In both cohorts, the percentage of participants who completed the eribulin portion of the regimen without a dose omission, delay or reduction due to eribulin-related AE was estimated via the observed completion rate and an exact 90% confidence interval (CI) was constructed.

Safety assessments consisted of monitoring and recording all AEs and SAEs, clinical laboratory results, vital signs, physical examinations, Eastern Cooperative Oncology Group (ECOG) performance status, electrocardiograms (ECGs), and left-ventricular ejection fracture (LVEF) by multigated acquisition scan (MUGA) or echocardiogram. An AE was considered a treatment emergent adverse event (TEAE) if the AE onset date was on or after the first dose of study drug and up to 30 days after receiving the last dose of study drug. Treatment-related TEAEs included TEAEs that were considered by the Investigator to be possibly or probably related to eribulin mesylate and/or doxorubicin/cyclophosphamide, or missing causality. Standardized Medical Dictionary for Regulatory Activities Queries (SMQ).

Eisai Inc.

Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) were reported. AEs were graded on a 5-point scale according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. All SAEs were reported, no fatal AEs, and all SAEs have CTCAE grade less than (\<) 4. The safety analysis set consisted of participants who were enrolled, received at least 1 dose of study treatments, and had at least 1 post-treatment safety assessment.

Participants initially received doxorubicin (60 mg/m\^2) plus cyclophosphamide (600 mg/m\^2) intravenously (IV) on Day 1, of every 14-day cycle for 4 cycles. Eribulin mesylate was administered following the doxorubicin plus cyclophosphamide regimen at a dose of 1.4 mg/m\^2 IV over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle for 4 cycles (Cycles 5 to 8). In this Cohort growth factors, subcutaneous pegfilgrastim (6 mg) or filgrastim, could be used with eribulin therapy at the physician's discretion if neutropenia occurred that recovered to Grade ≤2.

Cohort 1: Eribulin Mesylate With Filgrastim as Needed

Participants initially received doxorubicin (60 mg/m\^2) plus cyclophosphamide (600 mg/m\^2) IV on Day 1, of every 14-day cycle for 4 cycles. Eribulin mesylate was administered following the doxorubicin plus cyclophosphamide regimen at a dose of 1.4 mg/m\^2 IV over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle for 4 cycles (Cycles 5 to 8). In this Cohort filgrastim was used with eribulin therapy at a dose of 300 micrograms for participants ≤60 kg or 480 micrograms for participants \>60 kg, administered subcutaneously on Days 3 and 4 and Days 10 and 11 of each eribulin cycle.

Cohort 2: Eribulin Mesylate With Prophylactic Filgrastim

Total

Age, Continuous

Sex: Female, Male

Eisai Medical Information

The eribulin-treated analysis set included all participants who received at least 1 dose of eribulin mesylate at the starting dose of 1.4 mg/m\^2. This was the primary analysis set for the feasibility evaluation.

Percentage of Participants With Feasibility

All TEAEs

AC-related TEAEs

Eribulin-related TEAEs

Grade ≥3 TEAEs

SAEs

Alopecia

Neutropenia (SMQ)

Peripheral neuropathy (SMQ)

Participants initially received doxorubicin (60 mg/m\^2) plus cyclophosphamide (600 mg/m\^2) IV on Day 1, of every 14-day cycle for 4 cycles. Eribulin mesylate was administered following the doxorubicin plus cyclophosphamide regimen at a dose of 1.4 mg/m\^2 IV over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle for 4 cycles (Cycles 5 to 8). In this Cohort growth factors, subcutaneous pegfilgrastim (6 mg) or filgrastim, could be used with eribulin therapy at the physician's discretion if neutropenia occurred that recovered to Grade ≤2.

Participants initially received doxorubicin (60 mg/m\^2) plus cyclophosphamide (600 mg/m\^2) intravenously IV on Day 1, of every 14-day cycle for 4 cycles. Eribulin mesylate was administered following the doxorubicin plus cyclophosphamide regimen at a dose of 1.4 mg/m\^2 IV over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle for 4 cycles (Cycles 5 to 8). In this Cohort filgrastim was used with eribulin therapy at a dose of 300 micrograms for participants ≤60 kg or 480 micrograms for participants \>60 kg, administered subcutaneously on Days 3 and 4 and Days 10 and 11 of each eribulin cycle.

The Safety Analysis Set included all participants who were enrolled, received at least 1 dose of study treatments and had at least 1 post-treatment safety assessment. This was the primary analysis set for all safety evaluations including issues related to cyclophosphamide and doxorubicin (AC) or eribulin treatments.

Number of Participants With Non-serious Adverse Events and Serious Adverse Events (SAEs)

Participants initially received doxorubicin (60 milligram per square meter \[mg/m\^2\]) plus cyclophosphamide (600 mg/m\^2) intravenously (IV) on Day 1, of every 14-day cycle for 4 cycles. Eribulin mesylate was administered following the doxorubicin plus cyclophosphamide regimen at a dose of 1.4 mg/m\^2 IV over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle for 4 cycles (Cycles 5 to 8). In this Cohort growth factors, subcutaneous pegfilgrastim (6 mg) or filgrastim, could be used with eribulin therapy at the physician's discretion if neutropenia occurred that recovered to Grade ≤2.

Spots Global Cancer Trial Database for Dose Dense Doxorubucin and Cyclophosphamide Followed by Eribulin Mesylate for the Adjuvant Treatment of Early Stage Breast Cancer

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