A Study to Determine the Metabolism and Elimination of Carbon-14 Labeled Eribulin Acetate (14C-Eribulin) in Patients With Advanced Solid Tumors
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Intervention: eribulin
Intervention description: Cycle 1 day 1: radio-labeled dose of 2 mg radioactive eribulin, followed by 1.4 mg/m^2 of non-radio-labeled eribulin thereafter on days 1 and 8 every 21 days.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Solid Tumors; Failure of Multiple Prior Chemotherapy Regimens

Summary:

      The purpose of this study is to determine the metabolism and elimination of carbon-14 labeled
      eribulin acetate (14C-eribulin) in patients with advanced solid tumors.
    

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). Patients with measurable tumors according to
             RECIST are desirable but not essential.

          2. Patients must be aged 18 years or older.

          3. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of
             0,1, or 2.

          4. Patients must have adequate renal function as evidenced by serum creatinine ≤135 µM/L
             (≤1.5 mg/dL) or creatinine clearance >= 40 mL/minute (min).

          5. Patients must have adequate bone marrow function as evidenced by absolute neutrophil
             count (ANC) >= 1.5 x 10^9/L and platelet count >= 100 x 10^9/L.

          6. Patients must have adequate hepatic function as evidenced by bilirubin ≤ 1.5 times the
             upper limit of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT),
             and aspartate aminotransferase (AST) ≤ 3 x ULN (in the case of liver metastases ≤ 5 x
             ULN), unless there are bone metastases, in which case liver specific alkaline
             phosphatase must be separated from the total and used to assess the liver function
             instead of the total alkaline phosphatase.

          7. Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or
             below, except for stable sensory neuropathy ≤ Grade 2 and alopecia.

          8. Patients must be willing and able to comply with the study protocol for the duration
             of the study.

          9. Patients must give 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 any of the following treatments within the specified period
             before treatment start:

               -  chemotherapy, radiation, or biological therapy within three weeks

               -  hormonal therapy within one week

               -  any investigational drug within 4 weeks

               -  systemic unconventional or alternative therapies including, but not limited to,
                  herbal remedies within 4 weeks

          2. Have had radiation therapy encompassing > 30% of marrow.

          3. Have received prior treatment with mitomycin C or nitrosourea.

          4. Have had major surgery within 4 weeks before starting study treatment

          5. Patients with pulmonary lymphangitic involvement that results in pulmonary dysfunction
             requiring active treatment, including the use of oxygen.

          6. 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 in this study. Any signs
             (e.g., radiologic) and/or symptoms of brain metastases must be stable for at least 4
             weeks.

          7. Patients with meningeal carcinomatosis.

          8. 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) or international normalized ratio (INR) must be closely monitored.

          9. 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. Peri-menopausal women must be
             amenorrheic for at least 12 months to be considered of non-childbearing potential.

         10. Patients with severe/uncontrolled intercurrent illness/infection.

         11. Significant cardiovascular impairment (history of congestive heart failure > New York
             Heart Association (NYHA) grade II, unstable angina or myocardial infarction within the
             past 6 months, or serious cardiac arrhythmia).

         12. Patients with organ allografts requiring immunosuppression.

         13. Patients with known positive HIV status.

         14. Patients with pre-existing neuropathy > Grade 2.

         15. Patients with a hypersensitivity to halichondrin B and/or halichondrin B chemical
             derivative.

         16. Patients who participated in a prior eribulin clinical trial, whether or not they
             received eribulin (E7389).

         17. Patients with other significant disease or disorders that, in the Investigator's
             opinion, would exclude the patient from the study.