Study Of Eribulin (E7389) In Patients With Advanced Solid Tumors And Normal Or Reduced Hepatic Function As Per Child-Pugh System
Condition: Cancer
Intervention: E7389; E7389; E7389
Intervention description: E7389 Intravenous injection starting dose on Day 1 is 1.4 mg/m^2 for normal hepatic function.; E7389 Intravenous injection starting dose on Day 1 is 1.1 mg/m^2 for mild hepatic impairment (Child-Pugh A); E7389 Intravenous injection starting dose on Day 1 is 0.7 mg/m^2 for moderate hepatic impairment (Child-Pugh B)
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cancer; advanced solid tumors

Summary:

      This is an open-label, three-parallel group pharmacokinetic study. Patients with advanced
      solid tumors will be assigned to one of three groups to receive I.V. doses of eribulin
      (E7389). The three groups are: normal hepatic function, mild hepatic impairment (Child-Pugh
      A) and moderate hepatic impairment (Child-Pugh B) according to the Child-Pugh System for
      classifying hepatic impairment.
    

Eligibility criteria:

        Inclusion Criteria:

          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
             study

          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

        Exclusion 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
             scoring system.

          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
             http://medicine/iupui.edu/flockhart/table.htm.

          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
             compounds.

         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.