An Open-label, Parallel Group Study to Explore the Pharmacokinetics of Eribulin Mesylate (E7389) in Patients With Advanced Solid Tumors and Normal or Reduced Hepatic Function According to the Child-Pugh System
1. Patients must have a histologically or cytologically confirmed advanced solid tumor
that has progressed following standard therapy or for which no standard therapy
exists (including surgery or radiation therapy)
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
4. Life expectancy of ≥ 3 months
5. 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.
6. 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 is acceptable if it is
corrected by growth factor or transfusion), and platelet count ≥ 100 x 10^9/L
7. Patients willing and able to comply with the study protocol for the duration of the
8. Written informed consent prior to any study-specific screening procedures with the
understanding that the patient may withdraw consent at any time without prejudice.
Additional Inclusion Criteria for the Group of Patients with No Hepatic Impairment:
- All the general inclusion criteria listed above plus: Normal hepatic function as
evidenced by bilirubin ≤ 34 μmol/l (≤2.0 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), or in the case of bone
metastases, the liver specific alkaline phosphatase ≤3 times the upper limits of
normal (ULN), and in the case of concomitant liver metastases, ≤5 x ULN.
Additional Inclusion Criteria for the Group of Patients with Hepatic Impairment:
- All the general inclusion criteria listed above plus:
- Mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic dysfunction according to
the Child-Pugh scoring system criteria, where patients with laboratory values
within normal ranges will not be included in the Child-Pugh A category
- Or, Moderate hepatic dysfunction (Child-Pugh B) according to the Child-Pugh
scoring system criteria
1. Patients who have received any of the following treatments within the specified
period before E7389 treatment start:
1. Chemotherapy, radiation, biological therapy within 3 weeks.
2. Hormonal therapy within 1 week.
3. Any investigational drug within 4 weeks.
2. Patients with any clinically significant laboratory abnormality except for those
parameters influenced by hepatic impairment.
3. Patients with severe (Child-Pugh C) hepatic dysfunction according to the Child-Pugh
4. Patients with encephalopathy ≥ Grade 1.
5. Patients receiving any drug known to induce or inhibit CYP3A4 activity. Clinically
significant drugs are listed in a comprehensive list that can be found at
6. Patients, who require therapeutic anti-coagulant therapy other than for line patency
with warfarin or related compounds and cannot be changed to heparin-based therapy,
are not eligible.
7. 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.
8. Fertile men who are not willing to use contraception or fertile men with a female
partner who are not willing to use contraception
9. Severe/uncontrolled intercurrent illness/infection.
10. 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).
11. Patients with organ allografts requiring immunosuppression (not including blood and
blood components transfusions).
12. Patients with known positive HIV status.
13. Patients with brain or subdural metastases are not eligible, unless they are stable
and have completed local therapy and have discontinued the use of corticosteroids for
this indication for at least four weeks before starting treatment with E7389.
14. Patients with meningeal carcinomatosis.
15. Patients with a hypersensitivity to halichondrin B and/or halichondrin B-like
16. Patients who participated in a prior E7389 clinical trial.
17. Patients with preexisting neuropathy > Grade 2.
18. Patients with other significant disease or disorders that, in the Investigator's
opinion, would exclude the patient from the study.