A Phase II Study of E7389 in Patients With Breast Cancer, Previously Treated With Anthracycline, Taxane and Capecitabine

Breast Cancer Clinical Trial

Official title:

A Phase II Open Label Single-Arm Study of E7389 in Patients With Locally Advanced or Metastatic Breast Cancer, Previously Treated With Anthracycline, Taxane, and Capecitabine Therapy, Refractory to the Last Prior Therapy for Their Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00246090
• Other study ID #: E7389-G000-211
• Secondary ID: 2005-003656-35
• Status: Completed
• Phase: Phase 2
• First received: October 27, 2005
• Last updated: June 30, 2014
• Start date: October 2005
• Est. completion date: September 2007

Study information

• Verified date: April 2012
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEurope: European Agency for the Evaluation of Medicinal Products
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of E7389 in Patients with locally advanced or metastatic breast cancer, previously treated with anthracycline, taxane, and capecitabine as prior therapy, and who are refractory to the last prior therapy for their disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 298
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Female patients with histologically or cytologically confirmed carcinoma of the breast. Every effort should be made to make paraffin embedded tissue or slides from the diagnostic biopsy or surgical specimen available for confirmation of diagnosis.

2. Patients with locally advanced or metastatic disease who have received at least two (and not more than five) prior chemotherapeutic regimens for breast cancer, at least one of which was administered for treatment of locally advanced or metastatic disease.

Prior therapy must be documented by the following criteria prior to entry onto study:

• Regimens must have included an anthracycline (eg, doxorubicin, epirubicin), a taxane (eg, paclitaxel, docetaxel) and capecitabine in any combination or order.

• One or two of these regimens may have been administered as adjuvant and/or neoadjuvant therapy.

• Patients with human epidermal growth factor receptor 2 (HER2/neu) over-expressing tumors must additionally have been treated with trastuzumab.

• Patients with estrogen receptor-expressing tumors may have additionally been treated with estrogen-specific therapy.

• Prior hormonal therapy, biological therapy, (eg, trastuzumab, bevacizumab), or immunotherapy, is not to be counted as one of the 2 to 5 prior chemotherapy regimens allowed. However, hormonal therapy must be discontinued one week before administration of E7389, and biological therapy must be discontinued two weeks before E7389 administration.

• Patients who are being treated with bisphosphonates when they enter the study are allowed to continue the medication as long as the dosing does not change. In case a change in dosing is deemed necessary, the case needs to be discussed with the Sponsor.

3. Progression on or within six months of the last regimen for advanced disease, documented by the following:

• The dates of treatment, doses, outcome of therapy and the reason for discontinuation of prior anthracycline, taxane, capecitabine, and trastuzumab therapy must be provided.

• Prior to entry onto the study, information ensuring that the last therapy fulfills eligibility criteria is required, which includes progression while receiving this last prior chemotherapy regimen, or within six months of receiving that therapy.

• Chemotherapy medication administration sheets or other official medical/hospital records indicating type and dates of chemotherapy must be available for inspection, and one of the following as a reason for discontinuation of medication is required: radiographic evidence of progression, or doctor's office or hospitalization notes documenting radiologic progression, clinically documented increase in tumor burden, and/or increase in tumor-specific markers.

4. Patients with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, defined as at least one lesion that can be accurately measured in at least one diameter (at least 10 mm in longest diameter [LD] by spiral computer tomography [CT] scan), or at least 20 mm by standard techniques. If the only measurable lesion is a lymph node, it must measure at least 20 mm in LD. If a single lesion is identified as the target lesion, a biopsy or aspiration with cytological or histological confirmation of the diagnosis of breast carcinoma is required.

5. Resolution of all chemotherapy or radiation-related toxicities to less than Grade 2 severity, except for stable sensory neuropathy = Grade 2 and alopecia.

6. Age >= 18 years.

7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.

8. Life expectancy of = 3 months.

9. Adequate renal function as evidenced by serum creatinine = 2.0 mg/dL or calculated creatinine clearance = 40 mL/minute (min) per the Cockcroft and Gault formula.

10. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) =1.5 x 10^9/L hemoglobin = 10.0 g/dL (acceptable if it is corrected by therapeutic intervention or transfusional support), and platelet count = 100 x 10^9/L.

11. Adequate liver function as evidenced by bilirubin = 1.5 mg/dL and alkaline phosphatase, alanine transaminase (ALT), and aspartate transaminase (AST) = 3 times the upper limits of normal (ULN) (in the case of liver metastases = 5 x ULN), unless there are bone metastases, in which case liver specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of the total alkaline phosphatase.

12. Willing and able to complete the European Organization for Research on the Treatment of Cancer (EORTC) quality of life assessment, Analgesic Diary, and Pain Visual Analog Scale (VAS).

13. Willing and able to comply with the study protocol for the duration of the study.

14. Written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.

Exclusion Criteria:

1. Patients must not have received chemotherapy, radiation, or biologic therapy within two weeks, hormonal therapy within one week, or trastuzumab within three weeks, before E7389 treatment start.

2. Patients must not have received radiation therapy encompassing > 30% of marrow (a lesion that has been irradiated cannot be used as a target lesion, unless it has progressed after the irradiation).

3. Patients must not have pre-existing neuropathy > Grade 2.

4. Patients must not have participated in a prior E7389 clinical trial.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• E7389
E7389 1.4 mg/m^2 intravenous bolus given over 2-5 minutes on Days 1 and 8 every 21 days.

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences Juravinski Cancer Centre	Hamilton	Ontario
Canada	Centre Hospitaliere Universitaire de Montreal	Montreal	Quebec
Canada	McGill University, Dept. of Oncology, Clinical Research Program	Montreal	Quebec
Canada	NW Ontario Regional Cancer Centre	Thunder Bay	Ontario
Canada	Toronto East General Hospital	Toronto	Ontario
United States	New York Oncology Hematology, P.C	Albany	New York
United States	Harrington Cancer Center	Amarillo	Texas
United States	Peachtree Hematology And Oncology Consultants	Atlanta	Georgia
United States	Texas Oncology, P.A. Bedford	Bedford	Texas
United States	Birmingham Hematology and Oncology	Birmingham	Alabama
United States	Birmingham Hematology and Oncology	Birmingham	Alabama
United States	Charleston Hematology Oncology	Charleston	South Carolina
United States	University of Chicago	Chicago	Illinois
United States	Missouri Cancer Associates	Columbia	Missouri
United States	Center For Oncology Research and Treatment, PA	Dallas	Texas
United States	Sammons Cancer Center-Dallas	Dallas	Texas
United States	Texas Oncology PA	Dallas	Texas
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Rocky Mountain Cancer Center-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Center-Rose	Denver	Colorado
United States	North Shore Hematology Oncology Associates	East Setakuet	New York
United States	El Paso Cancer Treatment Center	El Paso	Texas
United States	El Paso Cancer Treatment Center West	El Paso	Texas
United States	Willamette Valley Cancer Center	Eugene	Oregon
United States	Fairfax Northern VA Hematology Oncology PC	Fairfax	Virginia
United States	Frederick Memorial Hospital, Regional Cancer Therapy Center	Frederick	Maryland
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Mercy Cancer Center	Hot Springs	Arkansas
United States	Baylor College of Medicine, Breast Cancer Clinic	Houston	Texas
United States	Texas Oncology PA	Houston	Texas
United States	Northwestern Carolina Oncology And Hematology, PA	Hudson	North Carolina
United States	Huntington Medical Group, PC	Huntington Station	New York
United States	Central Indiana Cancer Center	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	Wilshire Oncology Medical Group, Inc.	La Verne	California
United States	Arkansas Cancer Research Center	Little Rock	Arkansas
United States	Rocky Mountain Cancer Center	Littleton	Colorado
United States	'Signal Point Hematology/Oncology, Inc.	Middletown	Ohio
United States	Park Nicollet Institute	Minneapolis	Minnesota
United States	Montana Cancer Specialists	Missoula	Montana
United States	Monroe Medical Center	Munster	Indiana
United States	Weill Cornell Breast Cancer Center	New York	New York
United States	Cancer Care and Hematology Specialist of Chicagoland	Niles	Illinois
United States	Cancer Care Associates	Oklahoma City	Oklahoma
United States	Cancer Care Associates	Oklahoma City	Oklahoma
United States	North Texas Regional Cancer Center	Plano	Texas
United States	Cancer Research Network	Plantation	Florida
United States	Hematology-Oncology Associates	Port Saint-Lucie	Florida
United States	Kaiser Permanente, Central Interstate Clinic, Hematology Oncology	Portland	Oregon
United States	Northwest Cancer Specialist Hoyt	Portland	Oregon
United States	Northwest Cancer Specialist Rose Qtr	Portland	Oregon
United States	Raleigh Hematology Oncology Associates	Raleigh	North Carolina
United States	Oncology and Hematology Associates	Salem	Virginia
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	Cancer Care Northwest	Spokane	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Dr. Elizabeth Tan-Chiu, PA	Tamarac	Florida
United States	Medical University of Ohio	Toledo	Ohio
United States	Cancer Care Associates	Tulsa	Oklahoma
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialist	Vancouver	Washington
United States	Valley Oncology PA	Weslaco	Texas
United States	Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Eisai Inc.	Eisai Limited

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate	Based on Response Evaluation Criteria in Solid Tumors (RECIST), consisting of complete response (CR) plus partial response (PR). Defined as the best response from the start of treatment until disease progression or recurrence. Lesions measured by computed tomography (CT) scan and magnetic resonance imaging (MRI). Objective response rate: complete response (CR-disappearance of all lesions)+ partial response (PR-30% decrease in lesion diameter), Progressive Disease (PD-20% increase in lesion diameter), stable disease (SD-neither shrinkage nor increase of lesions).	Every two cycles	No
Secondary	Duration of Response	Complete response (CR) is defined as the disappearance of all lesions. Partial response (PR) is defined as 30% decrease in lesion diameter.	From first documented complete or partial response until disease progression or death	No