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Basic Trial Information
Trial Description
     Summary
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Active 18 and over Pharmaceutical / Industry E7389-G000-301 NCT00337103

Trial Description

Summary

This is an open-label, randomized, two-parallel arm study comparing E7389 with capecitabine. Patients will be randomized to receive either E7389 or capecitabine on a one-to-one ratio.

Eligibility Criteria

Inclusion Criteria:

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

2. Patients with locally advanced or metastatic disease who have received up to three prior chemotherapy regimens, and no more than two prior regimens for advanced disease. The regimes must have included an anthracycline and a taxane.

• Regimens must have included an anthracycline (e.g., doxorubicin, epirubicin) and a taxane (e.g., paclitaxel, docetaxel).

• If the treatment has been administered as adjuvant and/or neoadjuvant therapy, the patient must have relapsed during the treatment or within one year following the last dose of the most recent chemotherapy, and this must be documented.

• If the treatment has been administered for advanced or metastatic disease, the patient must have progressed during the last treatment or within six months of the last dose of the most recent chemotherapy, and this must be documented.

• Patients with known HER2/neu over-expressing tumors may additionally have been treated with trastuzumab in centers where this treatment is available.

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

3. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower, except for stable sensory neuropathy <= Grade 2 and alopecia.

4. Age >= 18 years.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Life expectancy of >= 3 months

7. Adequate renal function as evidenced by serum creatinine <1.5 mg/dL or calculated creatinine clearance > 50 mL/minute (min) per the Cockcroft and Gault formula.

8. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) >= 1.5 x 10^9/L, hemoglobin >= 10.0 g/dL (a hemoglobin < 10.0 g/dL acceptable if it is corrected by growth factor or transfusion), and platelet count >= 100 x 10^9/L.

9. Adequate liver function as evidenced by bilirubin <= 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine transaminase (ALT), and aspartate transaminase (AST) <= 3 x ULN (in the case of liver metastases <= 5 x ULN), or in case of bone metastases, liver specific alkaline phosphatase <= 3 x ULN.

10. Patients willing and able to complete the EORTC quality of life questionnaire (QLQ-C30 with breast cancer module QLQ-BR23) and pain VAS.

11. Patients willing and able to comply with the study protocol for the duration of the study.

12. 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 who have received more than three prior chemotherapy regimens for their disease, including adjuvant therapies, or patients who have received more than two prior chemotherapy regimens for advanced disease (other therapies are allowed e.g., anti-estrogens, trastuzumab and radiotherapy).

2. Patients who have received capecitabine as a prior therapy for their disease.

3. Patients who have received chemotherapy, radiation, or biological therapy within two weeks, or hormonal therapy, within one week before study treatment start, or any investigational drug within four weeks before study treatment start.

4. Radiation therapy encompassing > 30% of marrow.

5. Prior treatment with mitomycin C or nitrosourea.

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

7. Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment with study treatment. Any symptoms attributed to brain metastases must be stable for at least 4 weeks before starting study treatment; radiographic stability should be determined by comparing a contrast-enhanced CT or MRI brain scan performed during screening to a prior scan performed at least 4 weeks earlier.

8. Patients with meningeal carcinomatosis.

9. Patients who are receiving anti-coagulant therapy with warfarin or related compounds, other than for line patency, 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 ratio (INR) must be closely monitored.

10. 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 childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator. Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.

11. Severe/uncontrolled intercurrent illness/infection.

12. Significant cardiovascular impairment (history of congestive heart failure > New York Heart Association [NYHA] Grade II, unstable angina or myocardial infarction within the past six months, or serious cardiac arrhythmia).

13. Patients with organ allografts requiring immunosuppression.

14. Patients with known positive HIV status.

15. 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 >= 5 years previously with no subsequent evidence of recurrence.

16. Patients with pre-existing neuropathy > Grade 2.

17. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical derivative.

18. Patients who participated in a prior E7389 clinical trial.

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

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Objectives:

The primary objective of this study is to compare the efficacy of E7389 versus capecitabine monotherapy, in terms of Overall Survival and Progression-Free Survival in patients with locally advanced or metastatic breast cancer.

Secondary objectives are to assess:

• Quality of Life measured using the EORTC questionnaire

• Objective Tumor Response Rate as measured using RECIST criteria

• Duration of Response

• One, Two and Three year Survival

• Tumor Related Symptom Assessments measured by pain intensity (VAS), and analgesic consumption

• Safety Parameters (adverse events, laboratory parameters, concomitant medication, and study drug exposure)

• Pharmacokinetic/pharmacodynamic relationships in a population pharmacokinetic investigation in a minimum of 200 patients in the E7389 arm.

Trial Contact Information

Trial Lead Organizations/Sponsors

Eisai Incorporated

Corina Akerele, M.D.

Study Director

Eisai Eisai Medical Services

Ph: 1-888-422-4743

U.S.A.
California
	Anaheim
	Pacific Cancer Medical Center, Incorporated
Missouri
	Kansas City
	Kansas City Cancer Centers - South
New York
	Mount Kisco
	Westchester Hematology Oncology Associates

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00337103
Information obtained from ClinicalTrials.gov on July 16, 2008