Clinical trial NCT00246090: A Phase II Study of E7389 in Patients With Breast Cancer, Previously Treated With Anthracycline, Taxane and Capecitabine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Eisai Limited
First posted: 2005-10-30
Enrollment: 298
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: Every two cycles
Secondary outcomes:
measure: Duration of Response
timeFrame: From first documented complete or partial response until disease progression or death
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Hematology and Oncology
state: Alabama
city: Birmingham
country: United States
facility: Birmingham Hematology and Oncology
state: Alabama
city: Hot Springs
country: United States
facility: Mercy Cancer Center
state: Arkansas
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center
state: Arkansas
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Center-Midtown
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center-Rose
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Plantation
country: United States
facility: Cancer Research Network
state: Florida
city: Port Saint-Lucie
country: United States
facility: Hematology-Oncology Associates
state: Florida
city: Tamarac
country: United States
facility: Dr. Elizabeth Tan-Chiu, PA
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology And Oncology Consultants
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Niles
country: United States
facility: Cancer Care and Hematology Specialist of Chicagoland
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Center
state: Indiana
city: Munster
country: United States
facility: Monroe Medical Center
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Frederick
country: United States
facility: Frederick Memorial Hospital, Regional Cancer Therapy Center
state: Maryland
city: Minneapolis
country: United States
facility: Park Nicollet Institute
state: Minnesota
city: Columbia
country: United States
facility: Missouri Cancer Associates
state: Missouri
city: Missoula
country: United States
facility: Montana Cancer Specialists
state: Montana
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albany
country: United States
facility: New York Oncology Hematology, P.C
state: New York
city: East Setakuet
country: United States
facility: North Shore Hematology Oncology Associates
state: New York
city: Huntington Station
country: United States
facility: Huntington Medical Group, PC
state: New York
city: New York
country: United States
facility: Weill Cornell Breast Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Hudson
country: United States
facility: Northwestern Carolina Oncology And Hematology, PA
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Hematology Oncology Associates
state: North Carolina
city: Middletown
country: United States
facility: 'Signal Point Hematology/Oncology, Inc.
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: Cancer Care Associates
state: Oklahoma
city: Oklahoma City
country: United States
facility: Cancer Care Associates
state: Oklahoma
city: Tulsa
country: United States
facility: Cancer Care Associates
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Center
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialist Rose Qtr
state: Oregon
city: Portland
country: United States
facility: Kaiser Permanente, Central Interstate Clinic, Hematology Oncology
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialist Hoyt
state: Oregon
city: Charleston
country: United States
facility: Charleston Hematology Oncology
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Amarillo
country: United States
facility: Harrington Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology, P.A. Bedford
state: Texas
city: Dallas
country: United States
facility: Center For Oncology Research and Treatment, PA
state: Texas
city: Dallas
country: United States
facility: Texas Oncology PA
state: Texas
city: Dallas
country: United States
facility: Sammons Cancer Center-Dallas
state: Texas
city: El Paso
country: United States
facility: El Paso Cancer Treatment Center West
state: Texas
city: El Paso
country: United States
facility: El Paso Cancer Treatment Center
state: Texas
city: Houston
country: United States
facility: Texas Oncology PA
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine, Breast Cancer Clinic
state: Texas
city: Plano
country: United States
facility: North Texas Regional Cancer Center
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center
state: Texas
city: Weslaco
country: United States
facility: Valley Oncology PA
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Fairfax
country: United States
facility: Fairfax Northern VA Hematology Oncology PC
state: Virginia
city: Salem
country: United States
facility: Oncology and Hematology Associates
state: Virginia
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialist
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital
state: Washington
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Juravinski Cancer Centre
state: Ontario
city: Thunder Bay
country: Canada
facility: NW Ontario Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto East General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitaliere Universitaire de Montreal
state: Quebec
city: Montreal
country: Canada
facility: McGill University, Dept. of Oncology, Clinical Research Program
state: Quebec
Study officials:
affiliation: Eisai Inc.
name: Dale Shuster, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Muss H, Cortes J, Vahdat LT, Cardoso F, Twelves C, Wanders J, Dutcus CE, Yang J, Seegobin S, O'Shaughnessy J. Eribulin monotherapy in patients aged 70 years and older with metastatic breast cancer. Oncologist. 2014 Apr;19(4):318-27. doi: 10.1634/theoncologist.2013-0282. Epub 2014 Mar 28.