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. - E7389-G000-211

• Conditions: MedDRA version: 8.1Level: PTClassification code 10055113; ocally advanced or metastatic breast cancer

• Registration Number: EUCTR2005-003656-35-DE
• Lead Sponsor: Eisai Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-06-20
• Last Update Posted: 18 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 300

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 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 are 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 the last dose of 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 RECIST criteria, defined as at
least one lesion that can be accurately measured in at least one diameter (at least
10 mm in LD by spiral 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 or 2.

8. Life expectancy of = 3 months.

9. Adequate renal function as evidenced by serum cr

Exclusion Criteria

1. Patients who have received chemotherapy, radiation, or biological therapy within two weeks, or hormonal therapy within one week, before E7389 treatment start.

2. 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. Prior treatment with mitomycin C or nitrosourea, or prior stem cell transplantation.

4. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.

5. Patients with brain or subdural metastases are not eligible,except if they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment with E 7389.Any signs(eg,radiologic) and/or symptoms from their brain metastases must be stable for at least 4 weeks

6. Patients with meningeal carcinomatosis.

7. Patients who require anti-coagulant therapy, other than line patency, with warfarin or related compounds,and cannot be changed to heparin-based therapy,are not eligible. If a patient is to continue on mini-dose warfarin,then the prothrombin time(PT)/international normalized ration(INR) must be monitored closely.

8. Women who are pregnant or breast-feeding; women of childbearing potential with either a positive pregnancy test at screening or no pregnancy test. Women of child bearing potential unless (1) surgically sterile or (2) using adequate measures of contraception(two forms of contraception,at least one being a barrier method) in the opinion of the investigator. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.

9. Severe/uncontrolled intercurrent illness/infection.

10. Significant cardiovascular impairment (history of congestive heart failure >NYHA Grade II, unstabel angina or myocardial infarction within the past six month, or seriuos cardiac arrhythmia).

11. Patients with organ allografts.

12. Patients with known HIV status.

13. Patients who have had a prior malignancy, other than carcinoma in situ of the cervix, or non-melanoma skin cancer, unless the prior malignancy was diagnosed and definitively treated greater than or equal to 5 years previously with no subsequent evidence of recurrence.

14. Patients with pre-existing neuropathy > Grade 2

15. Hypersensitivity to halichondrin B and/or halicondrin B chemical derivative.

16. Patients who have previously been treated with E7389.

17. Patients with other significant diseases or disorders that, in the Investigator's opinion, would exclude the patient from the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified