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A Phase II Open Label Study of E7389 (Halichondrin B Analog) in Patients With Advanced/Metastatic Breast Cancer Previously Treated With Chemotherapy Including An Anthracycline and A Taxane

Phase 2
18 Years
Not Enrolling
Breast Neoplasms

Thank you

Trial Information

A Phase II Open Label Study of E7389 (Halichondrin B Analog) in Patients With Advanced/Metastatic Breast Cancer Previously Treated With Chemotherapy Including An Anthracycline and A Taxane

The primary objective is to determine the response rate (RR) to E7389 monotherapy
administered as an IV bolus of 1.4 mg/m^2 on Days 1, 8, and 15 of a 28-Day cycle and on Days
1 and 8 of a 21-day cycle in patients with advanced/metastatic breast cancer treated with
chemotherapy including an anthracycline and a taxane, with previously documented progression
during or within six months following the last dose of prior chemotherapy.

The secondary objectives are to evaluate:

- The safety and tolerability of E7389 monotherapy in this patient population;

- The antitumor activity of E7389 as determined by duration of response, time to
progression, and overall survival;

- Quality of life measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B)
questionnaire/tumor-related symptom improvement or worsening measured by pain intensity
on a visual analog scale (VAS), analgesics consumption, weight changes and performance
status (PS);

- Tumor pharmacogenetics and their possible relationship to response (assessment of
beta-tubulin isotype mRNA on biopsy sample) in patients who have signed a separate
consent form

Inclusion Criteria:

- Female patients with histologically or cytologically confirmed carcinoma of the

- Patients with advanced/metastatic disease that is not amenable to curative therapy
(either surgery or radiation therapy)

- Patients must have measurable disease by the 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
cytological or histological confirmation of breast carcinoma is required.

- Patients must have had prior treatment with an anthracycline and a taxane (either
sequential or in combination) and may have had prior treatment with other agents as

- Patients must have progressed within six months of the last dose of chemotherapy, or
experienced disease progression while receiving chemotherapy for advanced/metastatic

- Resolution of all chemotherapy or radiation-related toxicities to less than grade 1

- Age ≥ 18 years

- Eastern Cooperative Oncology Group (ECOG) Performance Status (APPENDIX 4) of 0 or 1

- Life expectancy of ≥ 3 months

- 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

- 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 would be acceptable if it can
be corrected by growth factor or transfusion), and platelet count ≥ 100 x 10^9/L

- 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)

- Patients willing and able to complete the FACT-B questionnaire, Analgesic Diary, Pain
VAS, and the tumor-related symptomatic assessment

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

- A sample from the diagnostic biopsy (paraffin block) must be available

- 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:

- Patients who have received chemotherapy, radiation, hormonal therapy, or Herceptin
within 2 weeks of E7389 treatment start

- Radiation therapy encompassing > 10% of marrow

- Failure to recover from any chemotherapy related or other therapy related toxicity at
study entry that is deemed to be clinically significant by the study investigator

- Prior treatment with Mitomycin C or nitrosoureas

- Prior high dose chemotherapy with hematopoietic stem cell rescue in the past two

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

- Active symptomatic brain metastasis; Patients with central Nervous System (CNS)
metastasis are considered eligible if they have completed local therapy and
discontinued from corticosteroids for at least two weeks before starting treatment
with E7389

- Patients with meningeal carcinomatosis

- Patients who require therapeutic anti-coagulant therapy with Warfarin or related
compounds; Mini dose warfarin for catheter related thrombosis prophylaxis is

- 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. Postmenopausal women must be
amenorrheic for at least 12 months to be considered of non-childbearing potential.

- Severe /uncontrolled intercurrent illness/infection

- Significant cardiovascular impairment (history of congestive heart failure > NYHA
grade II, unstable angina or myocardial infarction within the past six months, or
serious cardiac arrhythmia)

- Patients with organ allografts

- Patients with known positive HIV status

- 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

- Patients with pre-existing neuropathy > Grade 1

- Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical

- Patients who participated in a prior E7389 clinical trial

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

Type of Study:


Study Design:

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

Outcome Measure:

Overall Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST)

Outcome Description:

Defined as the percentage of subjects with CR or PR 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).

Outcome Time Frame:

Confirmed 4 to 8 weeks after first observed

Safety Issue:


Principal Investigator

Dale Shuster, Ph.D.

Investigator Role:

Study Director

Investigator Affiliation:

Eisai Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

September 2004

Completion Date:

November 2006

Related Keywords:

  • Breast Neoplasms
  • breast neoplasm
  • breast cancer
  • breast tumor
  • Breast Neoplasms
  • Neoplasms



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