Clinical trial NCT01328249: Dose Dense Doxorubucin and Cyclophosphamide Followed by Eribulin Mesylate for the Adjuvant Treatment of Early Stage Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER2-normal
Keywords: Breast Cancer
HER2-normal Stage I to III invasive breast cancer
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-04
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria

* Male and female subjects aged greater than or equal to (\>=) 18 years
* Histologically confirmed Stage I to III invasive breast cancer. Subjects may have more than one synchronous primary breast tumor.
* HER-2 normal as determined by fluorescence in situ hybridization (FISH) or 0 or 1+ by immunohistochemistry (IHC) staining.
* Subject is a candidate for chemotherapy in the adjuvant setting. Adjuvant therapy must begin within 84 days of the final surgical procedure for breast cancer.
* Adequate cardiac function, defined by baseline LVEF \>=50 percent (%) by Multiple Gated Acquisition (MUGA) scan or echocardiogram.
* ECOG performance status of 0 or 1.
* Adequate renal function as evidenced by serum creatinine less than or equal to (\<=) 1.5 mg/dL or calculated creatinine clearance \>=40 mL/min per the Cockcroft and Gault formula.
* Adequate bone marrow function as evidenced by ANC \>=1.5 x 10\^9/L, hemoglobin \>=10.0 g/dL, and platelet count \>=100 x 10\^9/L.
* Adequate liver function as evidenced by bilirubin \<=1.5 times the upper limits of normal (ULN) and alkaline phosphatase (AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) \<=3 x ULN.
* Females of childbearing potential must have a negative urine or beta-human chorionic gonadotropin serum pregnancy test within 2 weeks prior to Cycle 1, Day 1. A urine pregnancy test should be repeated prior to chemotherapy if not conducted within 72 hours of start of treatment. Female subjects of childbearing potential must agree to be abstinent or to use a highly effective method of contraception (e.g., condom + spermicide, condom + diaphragm with spermicide, intrauterine device (IUD), or have a vasectomized partner) having started for at least one menstrual cycle prior to starting study drug and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Perimenopausal women must be amenorrheic for at least 12 months to be considered of nonchildbearing potential. Male subjects who are not abstinent or who have undergone a successful vasectomy, who are partners of women of childbearing potential must use, or their partners must use, a highly effective method of contraception (e.g., condom + spermicide, condom + diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug and throughout the entire study period and for 30 days (longer if appropriate) after the last dose of study drug. Subjects with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously).
* Subjects willing and able to comply with the study protocol for the duration of the study and provide written informed consent prior to any study-specific screening procedures with the understanding that the subject may withdraw consent at any time without prejudice.

Exclusion Criteria

* Stage IV breast cancer.
* Prior chemotherapy, radiation therapy, immunotherapy, or biotherapy for current breast cancer.
* Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude any of the study therapy drugs.
* Subjects with a concurrently active second malignancy other than adequately treated nonmelanoma skin cancers or in situ cervical cancer.
* Subjects with known positive human immunodeficiency virus (HIV) status.
* Pregnancy or breast feeding at the time of study enrollment. Eligible subjects of reproductive potential (both sexes) must agree to use adequate contraceptive methods during study therapy.
* Subjects with known allergy or hypersensitivity to doxorubicin, cyclophosphamide, or eribulin mesylate.
* Inability to comply with the study and/or follow-up procedures.

Primary outcomes:
measure: Percentage of Participants With Feasibility
timeFrame: From date of first dose, up to 3 years after the last dose of study treatment, or up to approximately 4 years 2 months
Secondary outcomes:
measure: Number of Participants With Non-serious Adverse Events and Serious Adverse Events (SAEs)
timeFrame: From date of first dose up to 30 days after the last dose of study treatment, or up to approximately 4 years 2 months
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center ,Norris Cotton Cancer Center
state: New Hampshire
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
References: