Eribulin in Combination With Capecitabine for Adjuvant Treatment in Estrogen Receptor-Positive Early Stage Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase II, Multicenter, Single-Arm, Feasibility Study of Eribulin in Combination With Capecitabine for Adjuvant Treatment in Estrogen Receptor-Positive Early Stage Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01439282
• Other study ID #: E7389-A001-212
• Status: Completed
• Phase: Phase 2
• Start date: August 2011
• Est. completion date: May 2014

Study information

• Verified date: May 2016
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: May 2014
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Estrogen Receptor Positive Tumor

Intervention

Drug:
• eribulin mesylate
Cohort I & II: eribulin mesylate (E7389) 1.4 mg/m2 intravenously over 2 - 5 minutes on Day 1 and Day 8 for 4 cycles
• capecitabine
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

Locations

Country	Name	City	State
United States	New York Oncology Hematology, P.C.	Albany	New York
United States	Texas Oncology-Austin Central	Austin	Texas
United States	Sciode Medical Associates, PLLC, d.b.a. Eastchester Center	Bronx	New York
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology-Dallas Presbyterian Hospital	Dallas	Texas
United States	Texas Oncology-Medical City Dallas	Dallas	Texas
United States	Texas Oncology-Methodist Charlton Cancer Center	Dallas	Texas
United States	Texas Oncology- Denton South	Denton	Texas
United States	Texas Oncology-Fort Worth 12th Ave.	Fort Worth	Texas
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	Texas Oncology-Memorial City	Houston	Texas
United States	Texas Oncology-Lewisville	Lewisville	Texas
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Cancer Centers of Florida	Orlando	Florida
United States	Texas Oncology-Paris	Paris	Texas
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Evergreen Hematology and Oncology	Spokane	Washington
United States	Arizona Oncology Associates, PC - CASA	Tucson	Arizona
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Texas Oncology-Tyler	Tyler	Texas
United States	Northwest Cancer Specialists, P.C.	Vancouver	Washington
United States	Yakima Valley Memorial Hospital/North Star Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieved the Target Relative Dose Intensity (RDI) of 85%	Relative Dose Intensity (RDI) is defined as the amount of drug administered over a specific time and is expressed as the fraction of that recommended for standard of care. The RDI for each participant was calculated as follows: (1) based on each participant's body surface area (BSA), a total planned dose for both eribulin (Dep) and capecitabine (Dcp) calculated for a full 4-cycle regimen; (2) actual total dose of eribulin (Dea) and capecitabine (Dca) for the full 4-cycle regimen as collected on the case report form; (3) overall RDI = (Dea/Dep + Dca/Dcp)/2. For each individual participant, the regimen was considered feasible if that participant was able to achieve an RDI of at least 85% of the 4 cycles of eribulin plus capecitabine treatment. Missing doses due to any reason was counted as zero in the RDI calculation.	21-Day Cycle 1 through 21-Day Cycle 4
Secondary	Use of Cold Cap for Alopecia	Alopecia (hair loss) is a potential side effect of some chemotherapy agents. Chemotherapeutic drugs are toxic and could potentially harm the hair follicles (wear hair grows from) resulting in the hair falling out. It can occur in small patches on various parts of the body or all over the body and is usually temporary when related to cancer treatment. Cold cap therapy is one form of therapy for alopecia involving hair loss from the scalp. Wearing a cap or head covering with cold packs before, during, or after chemotherapy may help prevent hair loss as the cold narrows the blood vessels in the skin on your head which may lead to less of the drug reaching the hair follicles. Alopecia was one of the most common adverse events (AEs) related to eribulin only.	On the day of study drug infusion treatments during Cycles 1 through 4
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)		Day 1 through 30 days after last dose of study drugs (approximately up to 3 years)