Eribulin in Combination With Capecitabine for Adjuvant Treatment in Estrogen Receptor-Positive Early Stage Breast Cancer
Condition: Estrogen Receptor Positive Tumor; Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: eribulin mesylate; capecitabine
Intervention description: Cohort I & II: eribulin mesylate (E7389) 1.4 mg/m2 intravenously over 2 - 5 minutes on Day 1 and Day 8 for 4 cycles; Cohort 1: capecitabine 900 mg/m2 orally twice daily on Days 1 - 14 of a 21-day cycle for 4 cycles Cohort II: fixed dose of 1500 mg oral capecitabine twice daily, 7 days on then 7 days off for 4 cycles
Intervention MeSH terms: Capecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 77.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Estrogen Receptor-Positive Early Stage Breast Cancer

Summary:

      This is a Phase 2, multicenter, single-arm, feasibility study evaluating eribulin in
      combination with capecitabine as an adjuvant chemotherapy regimen in approximately 65
      subjects with early-stage (I-II), human epidermal growth factor receptor 2 (HER2)- normal,
      estrogen receptor (ER)-positive breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male subjects aged greater than or equal to 18 years and female subjects who must be
             postmenopausal (at least 12 months consecutive amenorrheic or have had a bilateral
             oophorectomy or, if they have had a hysterectomy but with ovaries intact, then females
             must be age 55 or older and with postmenopausal follicle-stimulating hormone [FSH]
             levels).

          2. 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.

          3. Histologically confirmed Stage I to II invasive breast cancer. Subjects may have more
             than one synchronous primary breast tumor.

          4. Receptor Status:

               -  HER2-normal as determined by a negative fluorescence in situ hybridization (FISH)
                  result or 0 to 1+ by immunohistochemistry (IHC) staining result

               -  ER-positive, node-negative or ER-positive Grade 1 or 2 node-positive breast
                  cancer

          5. ECOG performance status of 0 or 1

          6. Adequate renal function as evidenced by serum creatinine less than or equal to 1.5
             mg/dL or calculated creatinine clearance greater than or equal to 50 mL/min per the
             Cockcroft and Gault formula

          7. Adequate bone marrow function as evidenced by ANC greater than or equal to 1.5 x
             10^9/L, hemoglobin greater than or equal to 10.0 g/dL, and platelet count greater than
             or equal to 100 x 10^9/L

          8. Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the
             upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT),
             and aspartate aminotransferase (AST) less than or equal to 3 x ULN

          9. Male subjects must have had a successful vasectomy (confirmed azoospermia), or their
             female partners must not be of childbearing potential, or male subjects must agree to
             use and have their female partners use a highly effective method of contraception
             (e.g., total abstinence, an intrauterine device, a double-barrier method [such as
             condom plus diaphragm with spermicide] throughout the entire study period and for 30
             days after study drug discontinuation..

         10. Voluntary agreement to provide written informed consent and willingness and ability to
             comply with all aspects of the protocol

        Exclusion Criteria:

          1. Stage III and IV invasive breast cancer

          2. Prior chemotherapy, radiation therapy, immunotherapy or biotherapy for current breast
             cancer

          3. Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc) that would
             preclude any of the study therapy drugs

          4. Subjects with a concurrently active second malignancy other than adequately treated
             nonmelanoma skin cancers or in situ cervical cancer

          5. Subjects with pre-existing neuropathy greater than Grade 2

          6. Subjects with known positive human immunodeficiency virus (HIV) status

          7. Females of childbearing potential. Females will be considered to be of childbearing
             potential unless they are postmenopausal (at least 12 months consecutive amenorrheic
             or have had a bilateral oophorectomy or, if they have had a hysterectomy but with
             ovaries intact, then females must be age 55 or older and with postmenopausal FSH
             levels).

          8. Subjects with current gastrointestinal disease or other condition resulting in an
             inability to take or absorb oral medications

          9. Subjects with known allergy or hypersensitivity to eribulin mesylate or its
             excipients, or to fluoropyrimidine therapy (with or without documented
             dihydropyrimidine dehydrogenase [DPD] deficiency)

         10. A clinically significant electrocardiogram (ECG) abnormality, including a marked
             baseline prolongation of QT/QTc interval (time between the start of the Q wave and the
             end of the T wave/QT interval corrected for heart rate) (e.g., repeated demonstration
             of a QTc interval greater than 500 ms)

         11. Any medical or other condition which, in the opinion of the investigator, would
             preclude participation in a clinical trial